0% found this document useful (0 votes)

32 views29 pages

Nanostructured Materials For Artificial Tissue Replacements

Uploaded by

miazhang524

We take content rights seriously. If you suspect this is your content, claim it here.

Available Formats

Download as PDF, TXT or read online on Scribd

0% found this document useful (0 votes)

32 views29 pages

Nanostructured Materials For Artificial Tissue Replacements

Uploaded by

miazhang524

We take content rights seriously. If you suspect this is your content, claim it here.

Available Formats

Download as PDF, TXT or read online on Scribd

You are on page 1/ 29

International Journal of

Molecular Sciences

Review
Nanostructured Materials for Artificial
Tissue Replacements
Jana Pryjmaková 1 , Markéta Kaimlová 1 , Tomáš Hubáček 2 , Václav Švorčík 1 and Jakub Siegel 1, *
1 Department of Solid State Engineering, University of Chemistry and Technology Prague, Technická 5,
166 28 Prague, Czech Republic; [email protected] (J.P.); [email protected] (M.K.);
[email protected] (V.Š.)
2 Soil & Water Research Infrastructure, Biology Centre CAS, Na Sádkách 7, 370 05 České Budějovice,
Czech Republic; [email protected]
* Correspondence: [email protected]

Received: 28 January 2020; Accepted: 1 April 2020; Published: 5 April 2020

Abstract: This paper review current trends in applications of nanomaterials in tissue engineering.
Nanomaterials applicable in this area can be divided into two groups: organic and inorganic. Organic
nanomaterials are especially used for the preparation of highly porous scaffolds for cell cultivation
and are represented by polymeric nanofibers. Inorganic nanomaterials are implemented as they
stand or dispersed in matrices promoting their functional properties while preserving high level
of biocompatibility. They are used in various forms (e.g., nanoparticles, -tubes and -fibers)—and
when forming the composites with organic matrices—are able to enhance many resulting properties
(biologic, mechanical, electrical and/or antibacterial). For this reason, this contribution points
especially to such type of composite nanomaterials. Basic information on classification, properties
and application potential of single nanostructures, as well as complex scaffolds suitable for 3D tissues
reconstruction is provided. Examples of practical usage of these structures are demonstrated on
cartilage, bone, neural, cardiac and skin tissue regeneration and replacements. Nanomaterials open
up new ways of treatments in almost all areas of current tissue regeneration, especially in tissue
support or cell proliferation and growth. They significantly promote tissue rebuilding by direct
replacement of damaged tissues.

Keywords: nanomaterials; tissue engineering; biologic properties; mechanical properties; antibacterial

effects

1. Introduction
Nanomaterials, exceptional form of matter with dimensions as small as one billionth of meter, are
commonly defined with dimension range 1–100 nm. They may have different shapes and complex
morphologies which enable to classify them into three basic groups, i.e., 0, 1 and 2 dimensional
(0, 1 and 2D) nanomaterials as they are smaller than 100 nm in all directions, two axes or one axis,
respectively. Nanomaterials have many shapes, whereas the most common ones are nanoparticles
(0D) [1], nanowires (1D) [2], nanolayers (2D) [3]. All together, they represent basic building blocks or
active components in dynamically growing field of bioengineering.
Owing to their nanoscale dimension, nanomaterials possess properties resulting from critical
physical and chemical characteristics. This predetermines such materials for a wide range of utility in
biologic systems. Nanomaterials are used in tissue engineering [4], drug delivery [5], bioimaging [6],
gene therapy [7], etc. The other desired property is their large surface to volume ratio. It makes
nanoparticles (NPs) possible to go through the membrane and help cells absorb proteins [8–10]. For this
purpose, lipid [8], chitosan [9] and inorganic [10] (e.g., calcium phosphate, gold, carbon, silicon oxide

Int. J. Mol. Sci. 2020, 21, 2521; doi:10.3390/ijms21072521 www.mdpi.com/journal/ijms

Int. J. Mol. Sci. 2020, 21, 2521 2 of 29

and iron oxide) NPs have already been used. In that way, NPs can imitate the natural nanometer-size
scale extracellular matrix components and enables direct delivery of biologically active agents. Another
reason for the usage of different forms of nanomaterials in biologic applications is the alteration of
properties to required ones in tissue engineering.
Nanostructured materials may be of various origin and chemical composition organic and
inorganic ones. In tissue engineering, the organic nanomaterials often include polymeric nanofibers,
which may serve as a scaffold for cell cultivation [11]. More opportunities for such purposes represent
various inorganic nanomaterials [12]. By their incorporation into organic matrix scaffolds better
mimicking of physiological environment can be achieved. The resulting composites can show unique
properties required for assumed applications in hard and soft tissue engineering [13].
The aim of tissue engineering is to prepare biologically equivalent tissue or organ replacements.
The construction of the cell carriers (scaffold) is based on the knowledge of nanotechnology, but the
subsequent colonization of these carriers by the required population of cells is based on the knowledge
of cell and molecular biology and tissue physiology. So that, it is a multidisciplinary field that requires
understanding of both material and biochemical aspects important for prevention of undesirable
immune response of acceptor site of implant [14]. Thus, the material of the scaffold must be carefully
chosen, and for better cell conformity, the material properties properly modified [15]. Nowadays, there
are lot of well described nanostructured organic/inorganic composite materials for effective reparation
or replacement of portions or whole tissues (i.e., cartilage [16], bone [17], neural [18], cardiac [19] and
skin [20] tissue replacement etc.), where inorganic materials play irreplaceable role in the properties
modification. This review is predominantly focused on this type of composites.

2. Organic Nanomaterials
Organic materials applicable in tissue engineering are predominantly used as scaffolds for
a cell cultivation. The prevailing group of scaffold materials are polymers, especially polymeric
nanofibers [11]. Polymeric nanofiber networks are able to mimic the constitution of physiological
human tissue at the nanometer scale. The networks support cell adhesion, proliferation, migration and
differentiation with high efficacy, because they exhibit high surface-to-volume ratio [21]. Compared
with microfiber-based scaffolds, they excel in greater mechanical strength [22]. Nanofiber properties
depend on their orientation. Randomly oriented nanofibers increase material stiffness and mechanical
resistance in all directions. Contrary to that, arranged (so-called aligned) nanofibers enhance mechanical
properties only in the direction of their orientation [23]. Therefore, aligned polymeric nanofibers are
preferably applied in ligament [24], nerve [25] or muscle [26] regeneration with the aim to specify
the direction of tissue growth. Randomly oriented nanofibers find the applications in skin [27] and
cartilage [28] tissue engineering, where all directions of growth are necessary. For effective cell
cultivation, however, all kinds of polymeric nanofiber scaffolds must fulfill the following criteria:

• Porosity and pore size,

• Mechanical properties (e.g., strength and resistance),
• Biocompatibility,
• Susceptibility to attachment of cultivated cells,
• Biodegradability (in case of biodegradable materials),
• External geometry,
• Surface properties (surface area, roughness and charge),
• Capability to surface modifications [21].

Because the fields of application of polymeric nanofiber-based scaffolds is extensive and each of them
uses similar types of polymers, only one area, cartilage tissue replacement, will be described in detail.
Other areas of tissue engineering are mentioned in Table 1, together with commonly used polymers.
Cartilage tissue engineering effectively uses polymeric nanofibrous scaffolds for cultivation of
chondrocytes (CHs, cartilage-forming cells). High porosity of the scaffolds enables to locate cultivated
Int. J. Mol. Sci. 2020, 21, 2521 3 of 29

cells in required area, which has a great influence on reduction of implant failure. Moreover, scaffolds
could serve as a substrate for bonding of CHs, for which their anchorage is necessary for successful
adhesion [29]. 2D or 3D scaffolds can be used for the cultivation of chondrocytes. 2D cultivation (e.g.,
in Petri dishes) may lead to the cell’s dedifferentiation (cells undergo a reversal of differentiation and
lose specialized characteristics). Dedifferentiated cells then produce type I collagen instead of type II
one, which can be advantageously used in specific applications requiring this collagen type. 3D mode
of cultivation produces differentiated CHs with given phenotype and function. Thus, the advantage
of this mode of cultivation is the chondrocytes proliferation support with maintaining of important
cell functions [30]. Moreover, the use of scaffolds itself can practically accelerate and simplify the
cartilage tissue regeneration, because they may act as a supporting system for the migration of CHs
preserved in remaining tissue [31]. As the suitable materials for scaffolds, one can use natural, as well
as synthetic polymers.
Natural polymers, applicable in this field, include biodegradable materials, such as silk [31], chitosan [32],
hyaluronic acid [33], chondroitin sulphate [34], alginate [35], gelatin [36], cellulose [37] and bacterial
cellulose [38] and arbitrary combination of all of them. Unlike natural ones, synthetic polymers for
cartilage tissue replacement can be biodegradable, such as polyhydroxyethylmethacrylate (polyHEMA) [39],
polylactic acid (PLLA) [40] and its copolymers with polyglycolic acid (polylactic-co-glycolic acid, PLGA) [41]
or bioinert (e.g., polystyrene (PS) [42], polytetrafluoroethylene (PTFE) [43], polyethylene terephthalate
(PET) [44] and polyethyl- (PEMA) and methylmethacrylate (PMMA) [45]). Bioactive hydroxyapatite should
also be noted, which, however, does not belong to the category of organic materials [46].

Table 1. Selected areas of tissue engineering together with the cultivated cell types and examples of
polymers applicable as organic nanofibrous scaffolds for cell cultivation.

From the group of natural polymers, biodegradable silk fibrous proteins excel in unique mechanical
properties, especially processability, together with excellent biocompatibility, which makes silk a
suitable scaffold material for cartilage tissue engineering. Wang et al. [31] studied the influence of 3D
aqueous silk fibroin scaffolds on attachment, proliferation and differentiation of human chondrocytes
(hCHs) in vitro. They revealed that hCHs had spherical morphology similar to their cultivation in
physiological environment (in vivo), which promises their high effectivity in cartilage regeneration.
Another promising naturally occurring biodegradable material for this purpose is chitosan. Chitosan
is a natural aminopolysaccharide that degrades into simple sugars, which are the precursors of physiological
agents, such as glycosaminoglycans. In this manner the use of chitosan prevents foreign-body reactions
and implant rejection. Griffon et al. [32] compared chondrocyte proliferation and function between
chitosan and polyglycolic acid 3D scaffolds while using various pore size of chitosan sponges. They
found improving CHs proliferation and metabolic activity with increasing pore size, which improved
the diffusion of nutrients and cells throughout porous scaffold. Polyglycolic acid scaffolds produced
CHs with the morphology closer to natural cartilage, however, with significant risk of above-mentioned
material rejection. Combination of these two polymers may exhibit the benefits of both of them.
Biodegradable scaffold can effectively be made also from another natural polysaccharide,
hyaluronic acid (or its form hyaluronan). It is physiologically occurring major component of extracellular
matrix (ECM) in connective tissues, which provides their self-healing activity. Hyaluronic acid
improves proliferation of CHs, because it is able to interact with these cells via various surface
receptors with maintaining their original phenotype. Yoo et al. [33] prepared 3D hyaluronan
scaffolds by gas foaming/salt leaching method. Such scaffolds were seeded by bovine articular
chondrocytes and their adhesion, secretion of ECM, collagen synthesis and phenotypic characteristics
were studied. Hyaluronan prepared an optimal environment for the growth of CHs and saved them
from dedifferentiation process as well. In particular, collagen type II was found as a major characteristic
marker protein in formed hyaline cartilage tissue. The formation of hyaline cartilage tissue produced
CHs of native-like histological morphology having correctly differentiated phenotype.
Another component of animal cartilage tissue is mucopolysaccharide chondroitin sulphate, thus, it is
a suitable material for the preparation of scaffolds. It can be classified to the group of glycosaminoglycans
that covalently link to a protein core form proteoglycans. Due to these characteristics, chondroitin sulphate
plays a physiological role in the intracellular signaling, cell recognition and communication of ECM
with surface components of cells. Above that, chondroitin sulphate is able to direct cell orientation
and pathfinding. Chang et al. [34] investigated 3D chondroitin sulphate porous scaffolds by particulate
leaching. Because chondroitin sulphate is strongly water-soluble biodegradable polymer, it noticeably
increased water-binding capacity, which contributed to the spreading, migration and growth of CHs.
This phenomenon caused scaffold mimicking of the original environment.
Novel strategy, how to repair damaged cartilage, is the use of alginate. Alginate is a natural
polysaccharide, widely distributed component of the cell walls of brown algae as calcium, magnesium
or sodium salt of alginic acid. The most common calcium alginate is biodegradable, water-insoluble,
gelatinous substance efficient in entrapment of enzymes and suitable for tissue culture. Wang et al. [35]
prepared a highly organized 3D alginate scaffold for cartilage tissue engineering by microfluidic
technology. This technique produced alginate bubbles, which formed hollow beads and became highly
organized 3D ordered array structures. Their collection then formed a sponge-type, multiple-layer
alginate scaffold with uniform pore size, high swelling ratio and porosity. Alginate scaffold exhibited
no cytotoxicity to CHs, which exhibited normal cell phenotypes, proliferation and functionalization.
Ongoing animal studies suggest that this scaffold provide new possibilities for cartilage tissue
engineering in the near future.
Another novel material for this purpose is gelatin. Gelatin is a product of degradation of collagen,
which, besides others, is the major protein component of cartilage and ECM. Unlike to collagen, gelatin
has relatively low ability to trigger the immune system’s response by the production of antigens, which
makes it more suitable material for cartilage tissue replacement compared to its precursor. In addition,
Int. J. Mol. Sci. 2020, 21, 2521 5 of 29

gelatin can promote the information signals, which can improve cell adhesion, differentiation and
proliferation. Lien et al. [36] prepared 3D gelatin scaffolds of various pore sizes by crosslinking, seeded
them by articular CHs of Wistar rats, which were cultured in these scaffolds in vitro. They found that
the pore size of the scaffold increases with increasing crosslinking temperature. While the cells in
the scaffolds with the smaller pores were dedifferentiated, the larger pores better maintained their
phenotype. Chondrocytes also better proliferated with larger pore size and produced higher amount
of ECM in the group of scaffolds. Thus, the pore size was a key factor for cell metabolism.
The last natural polymer reported in literature as a suitable material for cartilage tissue engineering
is cellulose. Cellulose is the most widespread polysaccharide in nature, which is water-soluble at short
length of polymeric chains and can be biodegraded by enzymatic processes. Moreover, bioadhesive
cellulose in cartilage tissue engineering is easily processed to 3D scaffolds suitable for growing
functional CHs in vitro. These types of scaffolds were studied by Müller at al. [37]. They demonstrated
the ability of cellulose scaffolds to significantly enhance cell adhesion, proliferation and vitality,
indicating the excellent biocompatibility of this material. The distribution of the seeded CHs was
homogenous and proved the development of cartilaginous tissue. Measured production of calcium and
formation of the precipitated layer showed the development of microenvironment that ordinarily led
to reparation in the vicinity of subchondral bone in vivo. In particular, cellulose scaffolds were able to
repair not only the damaged cartilage, but also the subchondral bone, which integrate the neo-cartilage
into the osseous surrounding. A special kind of cellulose is bacterial cellulose, which is produced
by bacteria, such as Gluconacetobacter xylinus (also called Acetobacter xylinum). Bacterial cellulose,
as biodegradable natural polymer, is a novel biomaterial with unique properties including high water
holding capacity, high crystallinity, fine fiber network and high tensile strength. Svensson et al. [38]
reported response of primary bovine chondrocytes on bacterial cellulose. They found that 3D cellulose
scaffolds supported CHs proliferation at about 50% level and production of the collagen type II,
confirming that chondrocytes maintain their differentiated form, while the porosity of the material did
affect CHs viability. The scaffold supported cell ingrowth too. Moreover, bacterial cellulose did not
induce significant activation of proinflammatory cytokine production during in vitro testing. For these
reasons, bacterial cellulose exhibits potential for the application as scaffolds for tissue engineering
of cartilage. To preclude the disadvantages of individual polymers and ensure better mimicking of
natural environment, the combination of these materials can be effectively used for these purposes [75].
As natural polymers, the synthetic ones must also fulfill the conditions of biocompatibility, high
porosity and cell-adherence capability for their successful applications in cartilage tissue engineering.
They must act as a network on which the cells can proliferate, while preserving the shape of the
injured cartilage. One of the representatives of biodegradable synthetic polymers is polyHEMA.
PolyHEMA is a soft, flexible, water-absorbing polymer that forms a hydrogel in water. For the
applications, polyHEMA chains are often cross-linked into 3D network by another polymer to form a
copolymer. This leads to the formation of transparent material that absorbs up to 40% of water and
exhibits unique mechanical properties. Its application in intraocular contact lens is well established,
but such 3D network has also suitable properties as the scaffolds for cell cultivation. In this case, it
induces spheroid formation of cultured cells. Bölgen et al. [39] prepared biodegradable copolymer
polyHEMA–lactate–dextran (pHEMA–LLA–D)-based 3D scaffolds for cartilage tissue engineering and
studied its biocompatibility with bovine articular cartilage CHs in vitro. They revealed cells’ growth
on the surface and within the scaffolds, while most cells were attached to and integrated with the pores
of the scaffold. The chondrocytic morphology was round to oval-shaped. Cells rapidly proliferated,
secreted significant amount of ECM and were interconnected with each other by communication
junctions. Due to their unique properties, such as soft, elastic nature, highly open interconnected
pore structure and very rapid, controllable wettability, the pHEMA–LLA–D scaffolds are excellent
candidates for cartilage tissue regeneration.
Another synthetic, but natural-based biocompatible polymer is polylactic acid. PLLA is polymer
derived from lactic acid, which comes from renewable resources (fermented plant starch, such as
Int. J. Mol. Sci. 2020, 21, 2521 6 of 29

from corn, cassava, sugarcane or sugar beet pulp). PLLA undergoes hydrolytic deesterification to
lactic acid in vivo, which is a normal cellular metabolite that degrades by the Krebs’s cycle in lungs
into carbon dioxide and water. The absence of peptide linkages in polymeric chains minimizes
immunogenicity (ability to provoke an immune response). In particular, the biodegradation without
immunogenicity is the key factor, for the use of PLLA as a scaffold for cartilage tissue engineering.
Chu et al. [40] determined the suitability of porous D,D-L,L-polylactic acid as a 3D scaffold able to
repair cartilage tissue into full-thickness articular cartilage using rib perichondrium. By characterizing
both, the cell-polymer implant and the resulting repair tissue following implantation, the authors
demonstrated that perichondrocytes are able to attach to and survive within the scaffold and that a
consistent, cartilaginous-appearing repair was formed when implanted into drilled osteochondral
defects in a rabbit model. Thus, PLLA-based scaffold has the potential to create viable cartilage
healing. Novel approaches, however, combine polylactic acid with another biodegradable polyester,
polyglycolic acid, to gain better properties and ability to mimicking of cartilage tissue. The use of
PLGA copolymer enables to control of biodegradation period by the setting of various ratio of each
polyester. Moran et al. [41] studied the influence of such 3D scaffolds composition on the physical
properties, adhesion and growth of bovine articular CHs. They found that the compressive modulus of
scaffolds increased linearly with the addition of PLLA, as well as the biodegradation period (from 5 to
45 days). Addition of PLLA then decreased cell seeding efficacy and the morphology of cells changed
from flat to more round with increasing amount of polylactic acid. This study provided important
information for the design of scaffolds for cartilage tissue engineering.
The group of bioinert synthetic polymers for cartilage tissue engineering represents polystyrene
(PS). PS is non-biodegradable aromatic polymer that can exist in various forms. Tissue culture
polystyrene (TCPS), used for cell cultivation, is specific polystyrene modified by plasma treatment.
This inexpensive, disposable and transparent polymer is well known as cultivation standard. It improves
the attachment and proliferation of cells and enables their connection with other cells and ECM. Intra- and
extracellular communication then ensure cell apoptosis (programmed cell death), morphology, function
and differentiation. Binding of specific molecules, such as proteins (e.g., collagen) and polysaccharides
(heparin), on the surface of TCPS can mimic the biologic environment, from which the specific cell
type is derived (for more details see paragraphs below). Sato et al. [42] investigated the potential
of collagen/heparin-carrying polystyrene (HCPS) 3D scaffold for articular cartilage tissue engineering.
This scaffold built an optimal extracellular environment with a high-performance extracellular ECM
that enabled the aggregation of heparin-binding growth factors within the scaffold. Culture of rabbit
articular CHs exhibited high cell proliferative activity, because an extracellular environment was similar
to physiological one and heparan sulphate proteoglycan was generated within the HCPS scaffold.
Another synthetic polymeric material for non-absorbable scaffolds is polytetrafluorethylene.
Polytetrafluoroethylene (Teflon) is a synthetic thermoplastic fluoropolymer. It may exist in the form
of expanded PTFE (ePTFE), a material incorporating a fluoropolymer membrane with micropores,
which are necessary for the successful scaffold applications. Since ePTFE exhibits some inappropriate
properties for cell cultivation (e.g., hydrophobicity, see below), it needs to be modified before
application. Springer et al. [43] prepared ePTFE 3D scaffold containing polyamide monofilaments
with the aim to achieve non-absorbable scaffold material acting as a stress-absorbent network for
cartilage tissue-engineered transplants. They investigated the adhesion, spreading and ECM synthesis
of human and porcine CHs. Chondrocytes proliferated and spread vividly throughout scaffold,
differentiated predominantly into spherical shape and produced considerable amount of ECM. Authors
also identified collagen type II within the extracellular matrix, indicating no cell dedifferentiation.
Observed production of fibrocartilage-like tissue when being exposed to functional stress showed the
ability to balance the mechanical stress.
Polyethylene terephthalate can be also classified as a convenient synthetic bioinert material for
scaffolds. It is the most common thermoplastic polyester, which is advantageously used in various
application areas, because of its fiber-forming properties. Neves et al. [44] prepared polyethylene
Int. J. Mol. Sci. 2020, 21, 2521 7 of 29

terephthalate 3D scaffold formed from PET fabric with narrow size distribution of pores by stirring-induced
Int. J. Mol. Sci. 2019, 20, x FOR PEER REVIEW 7 of 29
mixing. They studied the similarity of the response of sheep menisci fibrochondrocytes on the scaffold to
the scaffold to
physiological physiological
meniscal meniscal
cartilage. Rapidcartilage. Rapid cell
cell proliferation withproliferation
maximal cell withdensities
maximalachieved
cell densities
within
achieved within the first seven days of cultivation, homogeneous cell distribution and the high levels
the first seven days of cultivation, homogeneous cell distribution and the high levels of collagen and
of collagen and glucosaminoglycans were observed. Thus, the synthetic meniscal construct a
glucosaminoglycans were observed. Thus, the synthetic meniscal construct successfully integrated into
successfully
repair site in theintegrated
knee thatinto canasupport
repair sitetheinquickness
the knee of that can support
healing in less thethanquickness
7 days was of healing
developed. in less
than 7 days
Novel was in
trend developed.
synthetic bioinert polymers for scaffolds represent polyethyl- and/or polymethyl-
Novel trend
methacrylate. These in synthetic
amorphous bioinert polymers
transparent for scaffolds
polymers exhibitrepresent
uniquepolyethyl-
mechanical and/or polymethyl-
properties and low
methacrylate.
water absorption These amorphous
capability. Due totransparent polymers exhibit
their biocompatibility and in unique mechanical
vivo stability, properties
they are used and low
in various
water absorption
implants and medical capability.
devices,Due to theirthey
in which biocompatibility and in vivo stability,
often form nanocomposites with PS theyand areorganically
used in
various clay
modified implants and medical
as emulsifier. devices,
Vikingsson in [45]
et al. which they long-term
studied often form nanocomposites
mechanical stabilitywith PS and
of a composite
organically modified clay as emulsifier. Vikingsson et al. [45] studied
scaffold containing a mixture of low molecular weight PEMA and PMMA and applicable in cartilage long-term mechanical stability
of a composite
defects. They exposed scaffoldthe containing a mixture ofcycles
scaffold to compression low molecular
and foundweight that thePEMA and PMMA
dry scaffold and a
failed after
applicable in cartilage defects. They exposed the scaffold to compression
smaller number of deformation cycles than water-immersed one, which was not affected by 100,000 cycles and found that the
dry scaffold failed after a smaller number of deformation cycles
compressive cycles. Water immersion simulated the physiological environment after implantation. than water-immersed one, which
was not affected by 100,000 compressive cycles. Water immersion simulated the physiological
Therefore, the scaffold is able to exhibit great mechanical performance when implanted in chondral
environment after implantation. Therefore, the scaffold is able to exhibit great mechanical
defects. This form of implantation of empty scaffold also supported the regeneration of new tissue
performance when implanted in chondral defects. This form of implantation of empty scaffold also
inside the scaffold’s pores.
supported the regeneration of new tissue inside the scaffold's pores.
In general, cells are sensitive to the surrounding environment, such as chemical composition
In general, cells are sensitive to the surrounding environment, such as chemical composition and
and morphologic aspects of the surfaces with which they are in a contact. Polymeric scaffolds
morphologic aspects of the surfaces with which they are in a contact. Polymeric scaffolds are
are advantageously used because of the excellent processability, biodegradability and other useful
advantageously used because of the excellent processability, biodegradability and other useful
properties,
properties, however,
however, thethe
suitability for for
suitability the applications
the applications in biologic media
in biologic must must
media be promoted
be promotedin majority
in
cases to better mimicking of physiological environment [45]. One approach,
majority cases to better mimicking of physiological environment [45]. One approach, how to achieve how to achieve required
properties, is the modification
required properties, of the polymeric
is the modification of thesurfaces.
polymeric Principally, the surface of
surfaces. Principally, thethe scaffold
surface is the
of the
primary site of interaction with surrounding cells and tissue. For this reason,
scaffold is the primary site of interaction with surrounding cells and tissue. For this reason, scaffolds scaffolds with a large and
with a large and accessible surface area, appropriate roughness and hydrophilicity are favorable [76].
accessible surface area, appropriate roughness and hydrophilicity are favorable [76]. These parameters
These
can parametersincreased
be effectively can be effectively increased of
by the exposure by polymeric
the exposure of polymeric
surface to excimersurface
laserto excimer
beam which laser is
beam
able which various
to create is able to create
forms ofvarious forms of on
nanostructures nanostructures
the surfaces of onaromatic
the surfaces of aromatic
polymers [77]. Thepolymers
surface
[77]. The surface
modification modification
in water environmentin water
leadsenvironment leads to
to the formation ofthe formation
worm-like of worm-like
structures, which structures,
passes to
which passesones
globular-like to globular-like
with increasing ones laser
with increasing
fluence (see laser fluence
Figure (see Figure
1) [78,79]. When1) [78,79].
exposing When theexposing
polymeric
the polymeric
surface to laser surface
beam under to laser beam angles
various under various angles
of incidence onofair,
incidence
one canon air, one
obtain the can obtain the
nanostructured,
nanostructured, highly-ordered periodic surface structures, such
highly-ordered periodic surface structures, such as ripples (Figure 1), whose periodicity increases as ripples (Figure 1), whose with
periodicity
increasing increases
incidence with(see
angle increasing
Figure 2) incidence
[80]. Theangleuse of (see
suchFigure 2) [80].for
structures Thetheuse
cellofcultivation
such structures
leads to
for the cell
orientation cultivation
of cells leadsofto
in direction theorientation
nanostructures. of cellsThisinphenomenon
direction of can theadvantageously
nanostructures. be This
used
phenomenon can advantageously be used in applications, where
in applications, where structured cellular arrays with influenced cell behavior is necessary [81]. structured cellular arrays with
influenced cell behavior is necessary [81].

Figure1.1.Various
Figure Various surface
surface nanostructures
nanostructures onto
onto polyethylene
polyethylene terephthalate
terephthalate induced
induced by by
KrFKrF excimer
excimer laser
laser irradiation,
irradiation, (a) worm-like,
(a) worm-like, (b) globular
(b) globular and and (c) ripple
(c) ripple structures.
structures. Measurements
Measurements werecarried
were carriedout
outby
by atomic
atomic forceforce microscopy.
microscopy.

Thesurface,
The surface,however,
however,exhibits
exhibitsboth
bothtopographical
topographicaland
andchemical
chemicalcharacteristics.
characteristics. Biocompatibility
Biocompatibility of
of polymeric
polymeric scaffolds
scaffolds canbe
can also also be improved
improved by the by the addition
addition of various
of various compounds,
compounds, which canwhich can be
be physically
physically
adsorbed or adsorbed
chemicallyorbounded
chemically
on bounded on scaffolds
scaffolds surface. The surface. The immobilization
immobilization of proteins, or
of proteins, saccharides
saccharides
other or othercompounds
physiological physiological compounds
forms specific forms specific
binding sites binding sites onto
onto scaffold scaffold
surface and surface and
may increase
may increase polymer hydrophilicity [45]. Thus, the resulting surface scaffold properties can be
selectively modified to optimize material properties for hosting cells. Cells are able to specifically
Int. J. Mol. Sci. 2020, 21, 2521 8 of 29

Int. J. Mol. Sci. 2019, 20, x FOR PEER REVIEW 8 of 29

polymer hydrophilicity [45]. Thus, the resulting surface scaffold properties can be selectively modified
recognize thematerial
to optimize binding properties
sites and their proliferation,
for hosting growth
cells. Cells are and/or differentiation
able to specifically can increase
recognize [76].
the binding
Another
sites andpossibility is the integration
their proliferation, growth and/orof differentiation
other biologically active compounds,
can increase [76]. Another which are isnot
possibility the
physiologically-based.
integration of other biologically active compounds, which are not physiologically-based. This unique
This group of materials represents inorganic nanostructures, whose group of
properties
materials are described
represents in following
inorganic text.
nanostructures, whose unique properties are described in following text.

Figure 2. Scheme of surface nanostructuring of polyethylene naphthalate (PEN) by KrF excimer laser
Figure 2. Scheme
irradiation ofincidence
under surface nanostructuring
angles of 0, 22.5ofand 45◦ [80]. naphthalate (PEN) by KrF excimer laser
polyethylene
irradiation under incidence angles of 0, 22.5 and 45° [80].
3. Inorganic Nanomaterials

3. Inorganic Nanomaterials
Inorganic nanomaterials for bioapplications are represented mainly by silica, metals, magnetic,
ceramic and carbon-based materials, especially in the form of nanoparticles and nanotubes (NTs).
Inorganic nanomaterials for bioapplications are represented mainly by silica, metals, magnetic,
Their applications in diverse areas of tissue engineering are summarized in Table 2 and described in
ceramic and carbon-based materials, especially in the form of nanoparticles and nanotubes (NTs).
following chapters. Other bioapplications of these nanomaterials, such as bioimaging [6], drug [4] and
Their applications in diverse areas of tissue engineering are summarized in Table 2 and described in
gene [82] delivery should be mentioned too. Especially nanoparticles find application as drug delivery
following chapters. Other bioapplications of these nanomaterials, such as bioimaging [6], drug [4]
containers, material reinforcements and agents controlling the release of bioactive molecules [4].
and gene [82] delivery should be mentioned too. Especially nanoparticles find application as drug
For the application of inorganic nanomaterials in the living organisms, one must consider all
delivery containers, material reinforcements and agents controlling the release of bioactive molecules
aspects which may lead to rejection of such artificial material by living body, even on the cellular level.
[4].
The most important property is biocompatibility. The material in a human body must be in harmony
For the application of inorganic nanomaterials in the living organisms, one must consider all
with ambient tissues and it must not trigger unwanted processes like organs dysfunctions, intoxication
aspects which may lead to rejection of such artificial material by living body, even on the cellular
or allergy. Biocompatibility of inorganic nanomaterials differs from that of “classic” bulk materials.
level. The most important property is biocompatibility. The material in a human body must be in
Because of their small size, they can enter body fluids (blood, plasma, extracellular matrix), where
harmony with ambient tissues and it must not trigger unwanted processes like organs dysfunctions,
they can interact with proteins [83]. Due to their affinity, they can be absorbed by cell organelles and
intoxication or allergy. Biocompatibility of inorganic nanomaterials differs from that of “classic” bulk
affect processes such as cell breathing, DNA transcription or transport abilities of cell membrane [84].
materials. Because of their small size, they can enter body fluids (blood, plasma, extracellular matrix),
Nanoparticles can also be combined with antibodies, which may increase their biologic effect [85].
where they can interact with proteins [83]. Due to their affinity, they can be absorbed by cell
Silica is biocompatible material with excellent chemical stability and surface properties [86,87].
organelles and affect processes such as cell breathing, DNA transcription or transport abilities of cell
Silica NPs can occur as individual objects for imaging or drug delivery or as coatings of other materials.
membrane [84]. Nanoparticles can also be combined with antibodies, which may increase their
The most known bioactive coating is tetraethyl orthosilicate. It can be combined with ammonium
biologic effect [85].
Silica is biocompatible material with excellent chemical stability and surface properties [86,87].
Silica NPs can occur as individual objects for imaging or drug delivery or as coatings of other
Int. J. Mol. Sci. 2020, 21, 2521 9 of 29

hydroxide and deionized water [88]. The size of silica nanoparticles can be affected by specific solution
composition, especially by water to ammonium hydroxide ratio. Size and shape depend on final
usages, so nanoparticles could be in the form of shells, mesoporous and bulk silica particles varying in
dimensions [87,89,90]. Mesoporous silica particles have broad range of desired properties, e.g., they
can absorb large amounts of biomolecules, and are able to resist to heat, pH changes, mechanical stress
and hydrolysis-induced degradations. These particles are also treasured for chemical and thermal
stability, simple fabrication and nontoxic nature [86,91].

Table 2. Overview of tissue engineering applications of inorganic nanomaterials and their main
advantages.

Nanostructure type Advantage RegeneratedTissue

Excellent biocompatibility,
Cartilage [92],
Silica NPs Uniform morphology,
Bone [93]
Chemical stability
Cartilage [94],
Excellent biocompatibility, Bone [95],
Gold NPs Low cytotoxicity, Neural [96]
Easy functionalization Cardiac [97],
Skin [98]
Antibacterial properties,
Bone [99],
Silver NPs Easy synthesis (various sizes and shapes)
Skin [100]
Low cost
Cartilage [16],
Excellent biocompatibility,
Bone [101],
Bioactivity,
Titanium dioxide NPs and NTs Neural [102]
Unique mechanical, thermal
Cardiac [103],
and electrical properties
Skin [104]
Cartilage [105],
Long-term efficacy, Bone [106],
Magnetic NPs Non-invasive application, Neural [107],
Superparamagnetic properties Cardiac [108],
Corneal [109]
Bioactivity, Cartilage [110],
Ceramic NPs Biodegradability, Bone [111],
Unique mechanical properties Cardiac [112]
Cartilage [113],
Double-sided functionality, Bone [114],
Carbon NTs,
Unique mechanical, thermal Neural [115],
Graphene and its oxide
and electrical properties Cardiac [116],
Pancreatic [117]

Metal nanoparticles represent dynamically developing group of nanomaterials which excel in

sensing, catalysts and therapeutic application, especially due to exceptional optical properties and
properties resulting from inner electron states, which completely differs from those known in bulk
counterparts. Within this group of nanomaterials gold nanoparticles occupy an exceptional position,
owing to their excellent biocompatibility and considerably low cytotoxicity [118]. Generally, metal
NPs exhibits unique antibacterial properties, well known for silver [119]. They may be synthesized in
many shapes and sizes, which can easily be identified by surface plasmon resonances visible in UV-Vis
spectra [120]. Despite of many favorable properties predetermining metal NPs for incorporation
in vast range of advanced functional products, their toxicity [1,121], biocompatibility [119,122],
bioremediation [123] and overall environmental impact must be constantly controlled during the
process of their synthesis, handling and especially at the end of their lifetime [124].
Int. J. Mol. Sci. 2020, 21, 2521 10 of 29

Strong UV absorption, mainly exploited in cosmetics, is well known for TiO2 nanoparticles. They
are able to preclude the penetration of sunlight into skin while remaining transparent layer [125].
Their combination with silica [126] and/or alumina [127] coatings prevent photocatalytic reactions.
Compared to other substances used for UV protection, TiO2 nanoparticles are one of the safest for
dermal exposure. However, the inhalation exposure may potentially bring a lung cancer risk, thus,
standard hazard controls for TiO2 nanoparticles are necessary [128].
Magnetic nanoparticles comply the Coulomb’s law. They can be manipulated (guided) by
an external magnetic field. They are applied in the transport and/or immobilization of magnetic
nanoparticles with magnetically bound biologic substances to the targeted area. By this way, the delivery
of anticancer agents to the tumor site is performed. This way of controlled drug delivery streamline the
treatment while reducing the side effects [129]. Moreover, energy transfer from the external magnetic
field to the magnetic NPs occurs, which leads to their heating and tumor cells are thermally destructed
due to hyperthermia [130]. Hyperthermia also cause the excellent antibacterial properties of magnetic
NPs by thermal destruction of bacterial cells [131]. As well, magnetic nanoparticles are used in
bioimaging for the increase of the contrast in magnetic resonance [132]. In bioapplications, classic
intrinsically magnetic materials, such as iron [131], but also semiconductors (magnesium oxide [133],
zinc oxide [134] and selenium NPs [135]) are commonly used. In particular, magnetic properties of
semiconductors can be achieved by the preparation of thin films with crystalline structure, which can
be deposited by magnetron sputtering. Magnetism without d-orbital electrons is based on polarization
induced by p-orbitals while the contribution of such developed defects to the resulting magnetism
is different when appear on the surface or subsurface layers of the crystalline thin film [136]. MgO
have this behavior associated with the spin triplet state of Mg vacancy and magnetic interaction occurs
through-bond spin polarization between two Mg vacancies [137]. The existence of spin-polarized
carriers in ZnO is the result of interactions between the conduction band and magnetic impurities (i.e.,
s-d exchange interaction in transition metal-doped ZnO) [138]. In case of Se (e.g., in organoselenium
compounds), mixing of σ and π orbitals results in a large paramagnetic contribution to the resulting
magnetism while chemical shift and spin–spin coupling can be observed [139].
Except of single oxide NPs (e.g., TiO2 , MgO and ZnO) described elsewhere, the group of bioceramic
nanomaterials consists of nanostructured hydroxyapatite [140], calcium-defective hydroxyapatite [141],
tricalcium phosphate [142] and bioactive glass (mixed oxides SiO2 -CaO-P2 O5 ) [112]. Chemical composition
of these materials is close to natural bone and tooth. Except the widespread applications for bone tissue
replacement [143], they can also serve as anti-erosive agent in toothpastes for the prevention of dentine
erosion and its remineralization support [140]. As applied in tooth implants, they excel with significant
antibiofilm activity. It plays an important role in the prevention of gingivitis [144]. Another application of
bioceramic nanoparticles is the controlled delivery of drugs or genes [145,146].
Bioapplicable carbon-based nanomaterials include carbon nanotubes [147], graphene [82] and
graphene oxide (GO) [117]. Carbon nanotubes represent rapidly growing biologically applied
nanomaterial in last decades. They can deliver drugs and genes, help in theranostics, biosensing
and in enhancement of microscopy resolution [147]. Carbon atoms are bonded in sp2 hybridization,
which gives CNTs good electrical and thermal conductivity and high mechanical and chemical stability.
They can exist as (i) single nanotubes with a diameter range of 0.4–2 nm or as (ii) multiwalled CNTs
with an external diameter range of 1.4–100 nm [148]. They can be conductive or nonconductive due
to their specific size. The toxicology of CNTs is not still clearly known, however, some pioneering
studies are warning about their harmfulness when exposed to rats [149]. Shape, length, surface charge,
diameter, purity and agglomeration are the factors, which predetermine level of CNTs toxicity [150].
Alike CNTs, graphene and its modified forms are favorable materials for bioapplications for their
unique properties. Graphene is a crystalline form of carbon represented by only one layer of sp2
hybridized orbitals tightly packaged into 2D hexagon grid. Each carbon atom has three σ-bonds and
one π-bond outside the plane that can bind to adjacent atoms [151]. In addition, graphene sheets
can be transformed into other conformation (e.g., GO) by chemical or physical modifications [117].
Int. J. Mol. Sci. 2020, 21, 2521 11 of 29

Moreover, graphene may be packaged into a form of 0D nanomaterial, such as fullerene or rolled into
1D nanotubes (1D), it may also form 3D graphite [152]. Each of these modifications has unique and
tunable properties, but they also exhibit a toxicity (similarly to CNTs). The properties of all described
carbon-based nanomaterial are exploited in bioimaging [6] and drug or gene delivery [82].

4. Opportunities of Properties Enhancement

The predominant group of scaffold materials for tissue cultivation forms polymeric nanofibers.
These organic materials, however, often exhibit inappropriate properties (for detail see Chapter 2).
The great opportunities for mimicking the physiological environment are gained by the incorporation
of inorganic nanomaterials [153] able to improve the design and functionality of resulting material and
thus, to overcome limiting factors of single material. The composite material design can be modified for
the applications locally in tissues, systemically throughout the body and at the interface with tissues.
Such modification requires detailed understanding of both biologic and material properties, which is
prerequisite of the development of more sophisticated biomaterials that achieving specific therapeutic
goals in tissue regeneration.

4.1. Biologic Properties

Gold nanoparticles (AuNPs) and titanium dioxide nanoparticles (TDNPs) provide high cell
proliferation rates for bone and cardiac tissue regeneration. Although AuNPs itself possess superior
biocompatibility, their properties may also be quite easily modified, which is especially interesting in
biomedical application [154,155].
They have been reported to assist in differentiation of osteoblast precursor cells [156], having
direct influence on osteoclast formation from hematopoietic cells during protective processes on
mitochondrial dysfunction [95]. The size of the AuNPs, however, has crucial influence on the cell
proliferation. While the particles in the range of 30–50 nm effect human adipose-derived stem cell
function [156], those of 20–40 nm size influence osteoblast-like cell function [157].
AuNPs have excellent properties for replacement of bone morphogenetic proteins. They exhibit
considerable effects on bone regeneration and promote repair processes in these tissues. However, high
cost, unwanted inflammatory reactions and uncontrolled bone formations make AuNPs candidates,
which still must be carefully developed to fit desired applications [158]. There have been some studies
pointing to promotion of osteogenic differentiation, when AuNPs are seeded in gelatin. With increasing
AuNPs concentration, the proliferation of osteoblasts was enhanced [159]. AuNWs may also direct stem
cell differentiation without distortion of growth factors [160]. This finding is revolutionary in the view of
functional organ transplantation due to minimizing the side effects of used growth factors in the body.
Enhancement of cell proliferation of human embryonic stem cell-derived cardiomyocytes can
also be accomplished by adding TiO2 nanoparticles to the scaffold [103]. TiO2 nanoparticles can be
also used in 3D printing technology of polymer as polylactic-co-glycolic acid to significantly improve
bone cell performance by matching the nanostructured roughness of bone itself. Moreover, TiO2
nanoparticles play an important role in preventing the harmful effects of dangerous products released
during PLGA degradation, which causes the cell death [101]. Promotion of biocompatibility by the
nanometal coating treatment of polymeric surface is shown in Figure 3.
Int.Int.
J. Mol. Sci.
J. Mol. Sci. 21,20,
2019,
2020, 2521
x FOR PEER REVIEW 1212ofof
29 29

Figure 3. Mouse embryonic fibroblasts L929 growing on the surface of (a) pristine polytetrafluoroethylene
Figure
and 3. Mouse embryonic
(b) polytetrafluoroethylene coatedfibroblasts L929 Images
by Au nanolayer. growing
wereontakenthe surface ofmicroscope
by fluorescent (a) pristine
at
polytetrafluoroethylene
magnification of 40×. and (b) polytetrafluoroethylene coated by Au nanolayer. Images were taken
by fluorescent microscope at magnification of 40×.
4.2. Mechanical Properties
4.2.Inorganic
Mechanicalnanoparticles
Properties may be used also as reinforcement improving scaffolds mechanical
properties. Several studies have
Inorganic nanoparticles may shown bethat
usedNPs-embedded artificial scaffolds
also as reinforcement improving (polymeric
scaffolds electrospun
mechanical
nanofibers and hydrogels) provided superior mechanical properties for tissue
properties. Several studies have shown that NPs-embedded artificial scaffolds (polymeric engineering application.
Scaffolds
electrospunwithout nanoparticle-reinforcement
nanofibers and hydrogels) did not provide
provided these mechanical
superior preferable properties
properties [161].
for Some
tissue
nanostructured forms of TiOScaffolds
engineering application. 2 , e.g., nanotubes,
without are treasured for their excellent
nanoparticle-reinforcement did properties
not provide as high
these
tensile strength, lower modulus, biocompatibility and excellent thermal stability.
preferable properties [161]. Some nanostructured forms of TiO2, e.g., nanotubes, are treasured for For improving
the mechanical
their excellentproperties
propertiesofasscaffolds used strength,
high tensile in skin tissue
lowerengineering, the 3D nanocomposites
modulus, biocompatibility are
and excellent
usually
thermal used, which consist
stability. of type I collagen
For improving and TiOproperties
the mechanical 2 nanoparticle-coated
of scaffolds polyvinylpyrrolidone
used in skin tissue
(PVP).
engineering, the 3D nanocomposites are usually used, which consist of 2type I collagenplay
In this mixture, the hydrogen bonds between collagen, PVP and TiO nanoparticles and the
TiO2
key role in increasing of tensile strength [104]. Not only
nanoparticle-coated polyvinylpyrrolidone (PVP). In this mixture, Au or TiO nanoparticles can be
2 the hydrogen bonds between used for
increasing
collagen,of mechanical
PVP and TiO2strength, but also
nanoparticles magnetite
play the key nanoparticles (MNPs)
role in increasing increase
of tensile the mechanical
strength [104]. Not
strength
only Au or TiO2 nanoparticles can be used for increasing of mechanical strength, but[162].
(e.g., MNP-seeded hydrogel microfibers with poly(N-isopropylacrylamide)) Due to
also magnetite
rapid developments
nanoparticles (MNPs) in increase
nanotechnology, there are
the mechanical many(e.g.,
strength otherMNP-seeded
examples ofhydrogel
mechanical properties
microfibers with
improvement in NPs-reinforced nanocomposites, where AuNPs, AgNPs, MNPs,
poly(N-isopropylacrylamide)) [162]. Due to rapid developments in nanotechnology, there are many TiO 2 NPs, CaCO 3
NPs, hydroxyapatite and PVA nanofibers, play a key role.
other examples of mechanical properties improvement in NPs-reinforced nanocomposites, where
AuNPs, AgNPs, MNPs, TiO2 NPs, CaCO3 NPs, hydroxyapatite and PVA nanofibers, play a key role.
4.3. Electrical Properties
4.3.Inorganic
Electrical Properties
nanoparticles with electrical properties can be utilized in cardiac and neural tissue
engineering [115,163]. Actually, AuNPs seem to be the most promising in this field. Shi et al. [164]
Inorganic nanoparticles with electrical properties can be utilized in cardiac and neural tissue
reported that deposition of AuNPs into fibrous decellularized matrices improved resulting morphology
engineering [115,163]. Actually, AuNPs seem to be the most promising in this field. Shi et al. [164]
of cardiac cells grown within these scaffolds. This provides better striation behavior and improved
reported that deposition of AuNPs into fibrous decellularized matrices improved resulting
electrical coupling of proteins. Afterwards, cardiac cells started proliferation through the 3D porous
morphology of cardiac cells grown within these scaffolds. This provides better striation behavior and
structure of scaffolds which resulted in synapse formation [165]. CNTs are also used as a conductive
improved electrical coupling of proteins. Afterwards, cardiac cells started proliferation through the
material in neural tissue engineering [166] and in composite with polymer for improving conductivity
3D porous structure of scaffolds which resulted in synapse formation [165]. CNTs are also used as a
in cardiac tissue engineering. For more about cardiac tissue engineering see below.
conductive material in neural tissue engineering [166] and in composite with polymer for improving
conductivity in cardiac tissue engineering. For more about cardiac tissue engineering see below.

4.4. Antibacterial Properties

Int. J. Mol. Sci. 2020, 21, 2521 13 of 29

Int. J. Mol. Sci. 2019, 20, x FOR PEER REVIEW 13 of 29

4.4. Antibacterial Properties
Nanostructured forms of heavy metals, such as silver [167], gold [168], copper [169] and others
Nanostructured forms of heavy metals, such as silver [167], gold [168], copper [169] and others [170],
[170], are able to exhibit strong antibacterial properties by the mechanism generally known as
are able to exhibit strong antibacterial properties by the mechanism generally known as oligodynamic
oligodynamic effect. This effect runs in low concentrations, in which the metals react with thiol or
effect. This effect runs in low concentrations, in which the metals react with thiol or amine groups
amine groups of bacterial proteins and form a covalent bond. Covalently bonded proteins then lose
of bacterial proteins and form a covalent bond. Covalently bonded proteins then lose their function
their function and bacterial cell perish [171]. The bioapplications of nanostructured heavy metals
and bacterial cell perish [171]. The bioapplications of nanostructured heavy metals require also
require also good biocompatibility, which is typically size-dependent [172]. The achievement of both,
good biocompatibility, which is typically size-dependent [172]. The achievement of both, strong
strong antibacterial activity and biocompatibility can be effectively exploited in various
antibacterial activity and biocompatibility can be effectively exploited in various bioapplications of
bioapplications of materials. Nowadays, these nanostructures are especially effective in the fight
materials. Nowadays, these nanostructures are especially effective in the fight against hospital-acquired
against hospital-acquired infections [119], which are commonly caused by frequently occurred
infections [119], which are commonly caused by frequently occurred environmental microorganisms,
environmental microorganisms, e.g., Gram-negative E. coli and Gram-positive S. epidermidis (see
e.g., Gram-negative E. coli and Gram-positive S. epidermidis (see Figure 4).
Figure 4).

Figure 4. Images of bacterial strains of E. coli and S. epidermidis taken by confocal microscopy (a)
Figure
and 4. Images
growing of bacterial
on agar strains
plates (b), of(left)
before E. coliand
andafter
S. epidermidis taken
(right side by confocal
of agar microscopy
plate) the treatment (a)
withand
Aggrowing on agar plates (b), before (left) and after (right side of agar plate) the treatment with Ag
nanoparticles.
nanoparticles.
Metal nanoparticles also combine antimicrobial effects and wound healing capabilities [173].
PresenceMetal nanoparticles
of silver also combine antimicrobial effects and wound
in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) healing capabilities
nanofibrous [173].
scaffolds
Presencethe
provided of antibacterial
silver in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibrous
activity, which significantly promoted cell compatibility. AgNPs scaffolds
can be
provided
also used inthe
bone antibacterial activity, as
tissue engineering which significantly
a supplement promoted cellscaffold.
in biocomposite compatibility. AgNPs
Scaffolds can be
and bone
also used in bone
silver-containing tissuecan
cements engineering as a supplement
regulate bacterial in biocomposite
infection during scaffold.ofScaffolds
the reconstruction andand
bone tissues bone
silver-containing
prevent inflammation cements canNot
[99,173]. regulate bacterial infection
only scaffolds, during the
but also implants reconstruction
represent of bone
potentially tissues
attractive
and prevent
groups inflammation
of materials [99,173].
in antibacterial Not only
treatment. scaffolds,
Thin nanolayerbutofalso implants
silver in formrepresent potentially
of nanoislands [3],
attractive groups
nanoparticles [174] orofnanowires
materials[175]
in antibacterial treatment.
serves as a protection Thininfection,
against nanolayer of silver
sepsis in form of
and malfunction
ofnanoislands [3],Composites
implants [173]. nanoparticles as [174] or nanowires [175]and
hydroxyapatite-AgNPs serves as a protection against infection,
hydroxyapatite/collagen-AgNPs sepsis
scaffolds
and developed
were malfunction of implants
as potential [173].
artificial graft Composites
materials as hydroxyapatite-AgNPs
for bone tissue engineering. In skin tissue and
hydroxyapatite/collagen-AgNPs
engineering, AgNPs have been successfully scaffolds were developed
applied as potential
to promote artificial
antibacterial graft materials
activity for
of carriers.
bone tissue engineering. In skin tissue engineering, AgNPs have been successfully applied to
promote antibacterial activity of carriers. The scaffold made of collagen and AgNPs was used for
burning healing, where silver particles helped to keep the congruent environment for successful
Int. J. Mol. Sci. 2020, 21, 2521 14 of 29

The scaffold made of collagen and AgNPs was used for burning healing, where silver particles helped
to keep the congruent environment for successful curing without inflammatory reactions [100]. From
the group of noble metals, Pd and Pt-based nanomaterials have been also repeatedly reported as
antibacterial promoting agents [176,177]. One of the many benefits of Pt oxides is less harmful impact
on the environment.
Not only the group of noble metals, but also magnetic nanoparticles have significantly effective
antibacterial properties. Magnesium oxide nanoparticles and their halogen adducts with Cl and Br [133,178]
consistently showed strong antibacterial properties. Results of the study showed that these nanoparticles
are effective towards three groups of bacteria: Escherichia coli, Bacillus megaterium and Bacillus subtilis.
The fascinating finding was the elimination of E. coli and B. megaterium bacteria in only 20 min. Another
antibacterial agent belonging to this category, selenium nanoparticles (SNPs), are very effective in killing
of bacteria by different mechanisms compared to e.g., silver ones [135]. Published results from live/dead
assays implied that the SNPs killed approximately 40% of S. aureus after 3 h. This inhibitory effect of
SNPs at early time points that SNPs may prevent S. aureus from forming biofilms. In addition, Iron oxide
nanoparticles are effective in destroying bacteria after biofilm formation [131]. They can penetrate the
biofilm (antibiotics cannot do this) and kill bacteria from the “inside”. Antibacterial effects of this group
of nanoparticles, however, occur only in the presence of a magnetic field, which brings them a great
application potential in tissue engineering.

5. Composite Organic/Inorganic Nanomaterials

In the field of tissue engineering, composite organic/inorganic materials are used as the hierarchical
3D scaffolds for cartilage, bone, neural, cardiac, skin and other tissues. In this view organic materials,
represented especially by polymeric nanofibers (as described in Chapter 2), serve as a matrix for the
integration of inorganic ones. Inorganic nanostructures can control adhesion and promote growth
and differentiation of cultivated cells. In the following text examples of the applications of such
organic/inorganic composites in the selected areas of tissue engineering are given.

5.1. Cartilage Tissue Engineering

As generally known, the cartilage of adults cannot be regenerated after an injury. This is caused by
the absence of vascular networks and chondrocytes, which cannot be caught on a dense extracellular
matrix. Thus, the healing potency of cartilage is limited. Moreover, synthesis of cartilage is very
difficult due to their low proliferation. Current materials engineering, however, must react on this
objective obstacle and offer the ways to enable preparation of artificial materials mimicking the function
and properties of natural cartilages, suitable for implantation [179]. For synthesis of artificial cartilages,
polymers are the best candidates, especially in the form of nanofibrous scaffolds (for more details see
Chapter 2). The scaffolds must mimic natural cartilage and support the growth of cells, with which the
integration of inorganic nanomaterials can significantly help.
Arjmandi et al. [92] integrated silica NPs into alginate-polyacrylamide (ALG-PAAm) polymeric
network (IPN) and investigated its potential to replace cartilage tissue. Resulting nanocomposite was
studied to obtain its mechanical and tribological characteristics in dependence on SiNPs concentration.
Authors determined ultralow coefficient of friction, high wear-resistance and tunable elastic and
viscoelastic behaviors. These characteristics were dependent on the interfacial binding between SiNPs
and ALG-PAAm matrix, enabling effective transfer of mechanical stress between these two components.
The most promising candidate for cartilage tissues replacement was the composite containing 4%
concentration of SiNPs, which exhibited the best mechanical properties.
Another example of suitable inorganic materials are magnetic nanoparticles. Zhang et al. [105]
prepared composite scaffold for cartilage tissue engineering from type II collagen, hyaluronic acid
and polyethylene glycol, incorporated by magnetic NPs. While exposed to external magnetic field,
the scaffold showed a reaction but maintain its structural integrity. Thus, remote magnetic direction
can deliver the material to repaired tissue by physiological fluids. As well, the adhesion density was
Int. J. Mol. Sci. 2020, 21, 2521 15 of 29

increased and cells exhibited normal and consistent morphology. Magnetic NPs may be then normally
metabolized, in other words may be broken down by lysosome and excreted through exocytosis.
This material closely mimics the microenvironment of extracellular matrix of cartilage tissue.
Last but not least, bioactive ceramic nanoparticles find the applications in cartilage reparation.
Kay et al. [110] investigated novel composite polylactic-co-glycolic acid scaffold doped by nanophase
ceramic for chondrocyte adhesion in vitro. Nanostructured material was prepared by chemical treatment
of microstructured PLGA. Compared with the conventional surfaces with micro-roughnesses, their
results provided the first evidence of increased CHs adhesion on PLGA surfaces with nano-roughness.
In particular, the study provided evidence that nanostructured PLGA/ceramic composites are able to
simulate the surface and/or chemical properties of physiological cartilage in nanoscale manner.

5.2. Bone Tissue Engineering

Due to increasing life expectancy and related development of civilization diseases there is
increasing proportion of people suffering from trauma, tumors or other diseases related to bones.
To cure those diseases and especially in bone repair, physicians often use autografts, allografts and
xenografts [180,181]. However, these treatments are not effective enough for bone reconstruction.
The way to success in healing is application of suitably chosen scaffold. The scaffold must support
the regeneration without complication. Its morphology and surface chemistry directly affect cell
attachment, proliferation and differentiation [182]. In bone tissue engineering, the scaffold must supply
and keep mechanical strength. To achieve these properties, preparation of material with the porous
network should be the best way. The porous structure promotes attachment of cells and subsequent
gripping of such artificial material in the bone [183].
Typically, the bone structure contains organic and inorganic components. The organic extracellular
matrix is usually strengthened by inorganic calcium phosphate nanoparticles and hydroxyapatite
crystals. Tricalcium phosphate is important for rigidity. Collagen type I and glycosaminoglycans are part
of the organic phase, which makes bone tough. For bone structure mimicking, inorganic nanomaterials
are the most commonly used entities. Nanohydroxyapatite, calcium silicate nanostructures, carbon
nanotubes or inorganic nanofibers can be easily formed into the necessary structure. As a replacement
of type I collagen, polymers are a good choice. Polymers are used usually as nanofibers. However, their
mechanical strength and biocompatibility are, lower compared to calcium phosphate ceramics [12].
Li et al. [111] studied porous scaffolds from nanohydroxyapatite, collagen and poly-L-lactic acid,
which were reinforced by chitin fibers. Cells caught on pores could grow and proliferate. The new
bone was built in 15 weeks after the operation. The porosity of scaffold is very important for ingrowing
of cells. In the study of Wei et al. [21] the influence of nano-scaled hydroxyapatite ratio on scaffolds
porosity was studied. The porosity decreases with higher addition of nanohydroxyapatite. The lowest
porosity was at least 89%, which is adequate for cells ingrowth.
Calcium phosphate and calcium silicate exhibit excellent biocompatibility and bioactivity. These
materials are grafted as bone substitutes, where they promote a creation of new bone [184]. Recently,
cement scaffolds were prepared containing calcium silicate and calcium phosphate. Sequential
testing showed that scaffold containing calcium phosphate had a hierarchically porous structure for
improvement of bone tissue regeneration [185]. On the other hand, calcium phosphate provided
retention of secondary structure and promoted bioactivity of such constructed scaffold. In the study
of Zhang et al. [186], calcium phosphate/calcium silicate bone cement with porous structure affected
significantly bone reformation. This study pointed out to higher osteogenic differentiation in vitro and
significant supporting of formation of the ectopic bone and regeneration of femur cavity defect in a rabbit
model. Biphasic calcium phosphate increased surface area and promoted proteins formation, including
bone-inducing proteins [187]. Among biogenic materials suitable for bone tissue engineering, glass
nanotubes are also excellent candidates due to promotion of cell differentiation and osteogenesis [188].
They enable ions delivering and stimulate the secretion of angiogenic growth factors.
Int. J. Mol. Sci. 2020, 21, 2521 16 of 29

Carbon-based nanomaterials occupy an important place in tissue engineering (Figure 5). The most
Int. J. Mol. Sci. 2019, 20, x FOR PEER REVIEW 16 of 29
utilized form of carbon is graphene and its derivatives. Of particular interest is graphene chemical
chemical Itstructure.
structure. It is a monolayer
is a monolayer of carbon
of carbon atoms atoms
packed packed
into into a 2D honeycomb
a 2D honeycomb lattice.
lattice. This This is
structure
structure is a base for other graphitic materials. Graphene and its derivatives possess a large surface
a base for other graphitic materials. Graphene and its derivatives possess a large surface area, high
area, high mechanical strength, intrinsic mobility, electrical conductivity and unparalleled thermal
mechanical strength, intrinsic mobility, electrical conductivity and unparalleled thermal conductivity.
conductivity.
Graphene is used Graphene is used as in
as a reinforcement a reinforcement
a hydrogel, filmsin fibers
a hydrogel, filmstypes
and other fibersof and othercontributing
scaffolds types of
toscaffolds
their higher contributing to theirand
mechanical strength higher mechanical
stiffness strength
[82]. Typical and stiffness
GO/hydroxyapatite [82]. show
hydrogels Typical
high
GO/hydroxyapatite hydrogels show high mechanical properties, high
mechanical properties, high electrical conductivity and primarily good compatibility [151].electrical conductivity and
primarily good compatibility [151].

Figure 5. Scheme of carbon nanotubes absorbing specific protein, promoting bone formation.
Figure 5. Scheme of carbon nanotubes absorbing specific protein, promoting bone formation.
5.3. Neural Tissue Engineering
5.3. Neural Tissue Engineering
Human nervous system forms complicated network of mutually interconnected neural cells.
One can Human nervoustwo
distinguish system
mainforms
partscomplicated
of this system network
(i) theofcentral
mutually interconnected
nervous system (CNS, neural cells.and
brain
One can distinguish two main parts of this system (i) the central nervous
spinal cord) and (ii) the peripheral nervous system (PNS, cranial and spinal nerves with ganglia). system (CNS, brain and
spinal cord)
Diseases and (ii)tissue
of nervous the peripheral nervous system
are very dangerous (PNS,
because of acranial
naturaland spinal nerves
property of nervouswithsystem
ganglia).
cells,
Diseases of nervous tissue are very dangerous because of a natural property
i.e., their zero possibility of healing. Parkinson’s disease, Alzheimer disease, stroke, brain tumor,of nervous system cells,
i.e., their brain
traumatic zero possibility of healing.
injury, infections Parkinson´s
(e.g., meningitis) disease,
are theAlzheimer
most common disease, stroke, affecting
diseases brain tumor,
neural
traumatic brain injury, infections (e.g., meningitis) are the most common diseases affecting neural
tissue. The regeneration of neural tissue makes problem in tissue injury healing. The PNS shows
tissue. The regeneration of neural tissue makes problem in tissue injury healing. The PNS shows some
some measure of generation property, but just in case of specific injuries. If the injury is larger and
measure of generation property, but just in case of specific injuries. If the injury is larger and
devastating, it must be surgically treated most often by limb transplantation. However, the number of
devastating, it must be surgically treated most often by limb transplantation. However, the number
donors is insufficient and it many cases is used to be even impossible to find suitable donor. Compared
of donors is insufficient and it many cases is used to be even impossible to find suitable donor.
to PNS, the CNS injuries cannot be treated in such easy way. Neural cells network in spinal cord
Compared to PNS, the CNS injuries cannot be treated in such easy way. Neural cells network in
are complex
spinal cord and very specific
are complex andspecific
and very currentand science stillscience
current cannotstill
prepare
cannotartificial
prepare structure mimicking
artificial structure
complex
mimicking function
complexof those
functioncells.
of In the cells.
those last few decades,
In the last few however,
decades,nanotechnologies provide new
however, nanotechnologies
materials suitable for cell migration and proliferation on the injury sites. For
provide new materials suitable for cell migration and proliferation on the injury sites. For healinghealing of the injuryofsite,
thethe injury site, the variety of stem cells can be used [189].
variety of stem cells can be used [189].
Forneural
For neural tissue
tissue healing,
healing, carbon
carbon nanotubes
nanotubes are are beneficially
beneficially usedused (Figure
(Figure 6). Single-walled
6). Single-walled carbon
carbon nanotubes
nanotubes have excellent
have excellent electrical
electrical conductivity,
conductivity, whichwhich makes makes possible
possible to support
to support andand control
control stem
stem
cells cells differentiation
differentiation towardtoward
neural neural
lineages lineages and promote
and promote the transmission
the signal signal transmission
between between
neurons.
Theneurons.
carbonThe carbon nanotubes
nanotubes are also
are also highly highly biocompatible
biocompatible for neuralfor neural regeneration
regeneration [115]. They [115].
canThey can in
be used
be used in combination
combination with lamininwith for laminin
creatingfor creating
a thin a thin
film for cellsfilm for cells supporting
supporting and proliferation
and proliferation in
in the synaptic
the synaptic connection [190]. For treating of injuries of nervous system
connection [190]. For treating of injuries of nervous system not only carbon nanotubes, but also not only carbon nanotubes,
but also
PLLA, PLLA,
acrylic acrylic
acid acid and have
and collagen collagen
beenhave been reported.
reported. Nanostructured
Nanostructured PLLA scaffolds
PLLA scaffolds make make
possible
thepossible
expansionthe expansion
of neural of neural
stem cellsstem cells [191–193]
[191–193] and present and collagen
present collagen
can mimic can the
mimic the natural
natural neuronal
neuronal extracellular matrix. Combination of collagen modified with methyl methacrylate and
acrylic acid in form of nanofibers provide a good environment for cells proliferation and
differentiation [194], too.
Int. J. Mol. Sci. 2020, 21, 2521 17 of 29

Int. J. Mol. Sci.

extracellular 2019, 20,Combination
matrix. x FOR PEER REVIEW 17 in
of collagen modified with methyl methacrylate and acrylic acid of 29
form of nanofibers provide a good environment for cells proliferation and differentiation [194], too.

Figure 6. Scheme of replacement of missing part of the neuron with graphene/PCL composite using
Figure
layer 6. Scheme
by layer castingof replacement of missing part of the neuron with graphene/PCL composite using
method.
layerTissue
5.4. Cardiac by layer casting method.
Engineering

5.4.
TheCardiac Tissue Engineering
cardiovascular diseases represent the greatest threat for today’s mankind. In the vast majority
of cases, when diagnosed at humans over 600 s, they are also the cause of death [195]. Almost 30 percent
The cardiovascular diseases represent the greatest threat for today’s mankind. In the vast
of people die on myocardial infarction. Thrombolytic treatment or surgical coronary artery bypass are
majority of cases, when diagnosed at humans over 60’s, they are also the cause of death [195]. Almost
most widespread used treatments of myocardial infarction. Such treatment, however, only supports
30 percent of people die on myocardial infarction. Thrombolytic treatment or surgical coronary artery
tissue regeneration. Myocardial infarction is caused by reduces blood supply to the heart, the cells
bypass are most widespread used treatments of myocardial infarction. Such treatment, however, only
without blood die, the tissue is damaged, which leads up to heart failure. So, the dead cells must be
supports tissue regeneration. Myocardial infarction is caused by reduces blood supply to the heart,
replaced by new functional ones. As the new cells, stem cells (mesenchymal, embryonic, induced
the cells without blood die, the tissue is damaged, which leads up to heart failure. So, the dead cells
pluripotent and cardiac) are often used [196], which replace the cardiomyocytes (CMCs), stops cell
must be replaced by new functional ones. As the new cells, stem cells (mesenchymal, embryonic,
dying and induce angiogenesis at the infarcted region (Figure 7).
induced pluripotent and cardiac) are often used [196], which replace the cardiomyocytes (CMCs),
Nanobiomaterials represent suitable matter for transportation of cells, proteins and genes for
stops cell dying and induce angiogenesis at the infarcted region (Figure 7).
cardiac repair [197]. Electrical, chemical or unique topographical characteristics are welcome for
Nanobiomaterials represent suitable matter for transportation of cells, proteins and genes for
creating of synergistic effects. Different combinations provide a lot of options for myocardial infarction
cardiac repair [197]. Electrical, chemical or unique topographical characteristics are welcome for
treating [163]. The function of the heart is possible due to cardiomyocytes, which are electrically
creating of synergistic effects. Different combinations provide a lot of options for myocardial
conductive. They receive the impulses from neurons, thereby making possible the right function of
infarction treating [163]. The function of the heart is possible due to cardiomyocytes, which are
heart and blood circulation. Unfortunately, most electrochemical therapies are unsuitable because they
electrically conductive. They receive the impulses from neurons, thereby making possible the right
may cause arrhythmias, which is uncoordinated contraction and stir conducting.
function of heart and blood circulation. Unfortunately, most electrochemical therapies are unsuitable
To achieve the right electrical conductivity of the heart tissue during and after the treatment,
because they may cause arrhythmias, which is uncoordinated contraction and stir conducting.
conductive nanobiomaterial-integrated therapeutics were developed with the same electrically
To achieve the right electrical conductivity of the heart tissue during and after the treatment,
conductive properties as cardiac tissue. The electrical conductivity is most commonly tested on
conductive nanobiomaterial-integrated therapeutics were developed with the same electrically
carbon- and gold-based nanomaterials. The cardiomyocytes [116] and cardiac progenitor cells [198]
conductive properties as cardiac tissue. The electrical conductivity is most commonly tested on
showed good adhesion and proliferation on the polymer scaffold with carbon nanotubes or nanofibers
carbon- and gold-based nanomaterials. The cardiomyocytes [116] and cardiac progenitor cells [198]
(CNFs). The conductive nanomaterials promote expression of Connexin 43, a gene with an important
showed good adhesion and proliferation on the polymer scaffold with carbon nanotubes or
role in heart development and repair. The mechanism of Connexin 43 upregulation is not yet completely
nanofibers (CNFs). The conductive nanomaterials promote expression of Connexin 43, a gene with
an important role in heart development and repair. The mechanism of Connexin 43 upregulation is
not yet completely clear. The understanding of therapy by conductive nanomaterials and the beating
behavior of the cells on a scaffold has been briefly explained by Martins et al. [199] and Kharaziha et
Int. J. Mol. Sci. 2020, 21, 2521 18 of 29

clear. The understanding of therapy by conductive nanomaterials and the beating behavior of the
Int. J.on
cells Mol.
a Sci. 2019, 20,has
scaffold x FORbeen
PEER briefly
REVIEW explained by Martins et al. [199] and Kharaziha et 18 al.of [200],
29
which investigated the electrophysiological behavior of cardiomyocytes seeded on a chitosan/CNFs
al. [200], which investigated the electrophysiological behavior of cardiomyocytes seeded on a
matrix or poly(glycerol sebacate)/gelatin/CNTs scaffolds, respectively. The cardiac cells have shown a
chitosan/CNFs matrix or poly(glycerol sebacate)/gelatin/CNTs scaffolds, respectively. The cardiac
synchronous beating behavior in contact with conductive nanomaterials. Increasing of expression of
cells have shown a synchronous beating behavior in contact with conductive nanomaterials.
cardiac-specific genes, cardiac muscle contraction and electrical coupling has occurred too. Therefore,
Increasing of expression of cardiac-specific genes, cardiac muscle contraction and electrical coupling
one can conclude, that the conductive materials provide the electrical coupling between cells and
has occurred too. Therefore, one can conclude, that the conductive materials provide the electrical
Connexin 43 and thus promote synchronous beating of the cardiac tissue. To improve the effectiveness of
coupling between cells and Connexin 43 and thus promote synchronous beating of the cardiac tissue.
therapy,
To improvegraphene NPs are alsoofutilized.
the effectiveness therapy,Hydrogel
graphene scaffold integrated
NPs are also with
utilized. AuNPsscaffold
Hydrogel [97] or integrated
AuNWs [19]
increases the Connexin 43 expression by cardiomyocytes compared to CMCs cultured
with AuNPs [97] or AuNWs [19] increases the Connexin 43 expression by cardiomyocytes compared in hydrogel
without
to CMCs those nanomaterials.
cultured in hydrogel without those nanomaterials.

Figure7.7.The
Figure Thetherapeutic
therapeutic mechanism of dead
mechanism of deadcells
cellsreplacement
replacementinincardiac
cardiac tissue
tissue byby stem
stem cells.
cells.

5.5. Skin Tissue Engineering

5.5. Skin Tissue Engineering
Despite that skin tissue represents an insignificant part of total body weight, skin injuries, such
Despite that skin tissue represents an insignificant part of total body weight, skin injuries, such
asas
burns
burns[201]
[201]and
anddiabetic
diabeticulcers
ulcers [202],
[202], lead
lead to
to the seriousrisks.
the serious risks.Therefore,
Therefore,skinskin tissue
tissue engineering
engineering
plays an irreplaceable role in the treatment of chronic skin wounds. The
plays an irreplaceable role in the treatment of chronic skin wounds. The application of skin application of skin tissue
tissue
replacement
replacementmust mustbe beeasily
easilyaccomplished
accomplished to rapid location
to rapid locationand andcover
coverthe
thewound.
wound. Then
Then thethe skin
skin cells
cells
must strongly adhere. For this reason, artificial skin tissue replacements must exhibit appropriate
must strongly adhere. For this reason, artificial skin tissue replacements must exhibit appropriate
physical
physical andmechanical
and mechanicalproperties
properties to to mimic
mimic physiological
physiologicalskin skinand
andbebenonantigenic.
nonantigenic. Such
Suchprepared
prepared
replacementthen
replacement thenassimilates
assimilatesinto
into the
the body while
while regenerating
regeneratingthe thenewnewskin
skintissue [203].
tissue Nowadays,
[203]. Nowadays,
skin
skin tissueengineering
tissue engineeringdevelops
develops andand designs
designs novel
novel polymeric-based
polymeric-basedscaffolds
scaffolds containing
containing inorganic
inorganic
nanoparticles with enhanced mechanical [104] and added antibacterial
nanoparticles with enhanced mechanical [104] and added antibacterial [100] properties. [100] properties.
LiLiet et
al. al. [104]
[104] developed
developed nanocomposite
nanocomposite polymer/TiO
polymer/TiO 2 scaffold
2 scaffold with with enhanced
enhanced stability
stability as a
as a potential
potentialfor
substrate substrate for skin
skin tissue tissue cultivation.
cultivation. Their 3Dwas
Their 3D scaffold scaffold was prepared
prepared by freezeby freezeofdrying
drying of the of
the mixture
mixture
type of type
I collagen andI polyvinyl
collagen and polyvinyl(PVP)-coated
pyrrolidone pyrrolidone TiO(PVP)-coated TiO2 nanoparticles. This method
2 nanoparticles. This method generated highly
generated highly porous scaffold without the use of cross-linkers or
porous scaffold without the use of cross-linkers or toxic reagents. The swellability, toxic reagents. The swellability,
mechanical properties
mechanical properties and hydrolytic degradation of the nanocomposite
and hydrolytic degradation of the nanocomposite scaffolds were the key determined parameters. scaffolds were theAuthors
key
determined
refers parameters.
that collagen, PVP and Authors refersbonded
TiO2 were that collagen,
by fourPVP and TiObonds,
hydrogen 2 were bonded by four hydrogen
which increased the scaffold
bonds, which increased the scaffold stability. The stability was dependent on the amount of the added
stability. The stability was dependent on the amount of the added PVP. The complex composition
PVP. The complex composition containing TiO2 NPs increased resulting tensile strength of the
containing TiO2 NPs increased resulting tensile strength of the scaffold, which was four times higher than
scaffold, which was four times higher than that based on simple collagen.
that based on simple collagen.
Int. J. Mol. Sci. 2020, 21, 2521 19 of 29
Int. J. Mol. Sci. 2019, 20, x FOR PEER REVIEW 19 of 29

Recent
Recentresearch predominantly
research predominantly emphasizes
emphasizesaddition of antibacterial
addition effectseffects
of antibacterial to polymeric scaffolds
to polymeric
scaffolds with the aim to preclude the injured skin inflammation. This capability is well known silver
with the aim to preclude the injured skin inflammation. This capability is well known for for
silver nanoparticles
nanoparticles (Figure(Figure 8a). They,
8a). They, incorporated
incorporated into into polymeric
polymeric matrix
matrix (Figure
(Figure 8b),
8b), cancan increasethe
increase
the healing
healing ability
ability of of the [20,78].
the material materialPatrascu
[20,78]. et
Patrascu
al. [100]etstudied
al. [100] studied homogenous
homogenous and heterogeneous and
heterogeneous scaffold materials containing silver nanoparticles for their antiseptic behavior.
scaffold materials containing silver nanoparticles for their antiseptic behavior. Polymeric matrices
Polymeric
were based on matrices wereSilver
collagen. basedNPson collagen. Silver NPs
were synthetized bywere synthetized
chemical reaction bytochemical reaction with
obtain material to
obtain material
homogenous with homogenous
distribution of AgNPsdistribution
and plasma of sputtering
AgNPs andfor plasma sputteringone.
heterogenous for heterogenous
In vitro assays
one. Insignificant
revealed vitro assays revealed significant
antibacterial antibacterial
activity against activity
Escherichia against
coli at Escherichia coli of
low concentrations at AgNPs
low
concentrations of AgNPs (10 ppm). Thus, they developed strong antiseptic materials
(10 ppm). Thus, they developed strong antiseptic materials with the potential to repair skin injuries, with the
potentialcaused
especially to repair skin injuries,
by burns especially
or cancer. For thecaused
healingby of burns
already orrunning
cancer. For the healing
infection, Ag-rich of side
already
of the
running infection, Ag-rich side of the material must be in the contact with treated tissue.
material must be in the contact with treated tissue. For the protective role against potential infection, For the
protective
both role against
homogenous potential infection,
and heterogenous both homogenous
materials are suitable,and heterogenous
because the contactmaterials are suitable,
of Ag-rich side with
because the contact of Ag-rich side with the skin is not necessary.
the skin is not necessary.

Figure8. 8. Images
Figure Images of
of electrochemically
electrochemically synthetized
synthetizedAgNPs
AgNPs(a)(a)and
andAgNPs
AgNPsimmobilized
immobilizedonto
onto
polyethyleneterephthalatesurface
polyethyleneterephthalate surface by
by KrF
KrF excimer
excimer laser
laser(b),
(b),measured
measuredbyby
transmission andand
transmission scanning
scanning
electron
electron microscopy,
microscopy, respectively.
respectively.

6. 6. Challengesand
Challenges andFuture
FuturePerspectives
Perspectives
Nanomaterials
Nanomaterials cancan be used
be used in widein range
wide ofrange of bioapplications.
bioapplications. This review This review
focuses focuses on
on nanomaterials
nanomaterials
applicable applicable
in tissue in tissue
engineering. engineering.
In addition In addition
to these to thesenanomaterials
applications, applications, nanomaterials
open up new waysopen of
up new ways
bioimaging of bioimaging
as well as well
as drug or gene as drug
targeted or gene
delivery. Intargeted delivery. Inthe
all bioapplications, all nanomaterials
bioapplications, the
provide
nanomaterials provide advantageous properties, such as enhanced cell adhesion,
advantageous properties, such as enhanced cell adhesion, proliferation and growth in diverse areas of proliferation and
growth
tissue in diverseEspecially,
engineering. areas of tissue
theyengineering.
significantlyEspecially, they significantly
promote cartilage, promote
bone, neural, cartilage,
cardiac and skinbone,
tissue
neural, cardiac
rebuilding andreplacement
by direct skin tissue rebuilding
of damaged byportions
direct replacement of damaged
or whole tissues. These portions
fields of or whole
application
aretissues. These
specific by thefields of application
sensitivity are specific
of regenerated by the
tissue sensitivity
to artificial of regenerated
materials tissue to artificial
and subsequent possibility
materials and subsequent possibility of immune response. Possible risks
of immune response. Possible risks and obstacles may be overcome by excellent biocompatibilityand obstacles may be of
overcome by excellent biocompatibility of inorganic nanomaterials in the forms of single
inorganic nanomaterials in the forms of single nanoparticles or nanotubes and their incorporation
nanoparticles or nanotubes and their incorporation into organic (polymeric nanofibrous) scaffolds.
into organic (polymeric nanofibrous) scaffolds. However, there is another quite worrying point: the
However, there is another quite worrying point: the long-term bioaccumulation of nanoparticles in
long-term bioaccumulation of nanoparticles in the human body can cause the diseases of unknown
the human body can cause the diseases of unknown etiologies resulting from their toxicity and
etiologies resulting from their toxicity and leading to harmful effects on reproductive organs, fetal
leading to harmful effects on reproductive organs, fetal development disorders or cancer. Sometimes,
development disorders or cancer. Sometimes, we cannot control each property or predict the behavior of
we cannot control each property or predict the behavior of cells. Therefore, despite the undoubted
cells. Therefore,
benefits despite the undoubted
that nanomaterials may bring benefits
to the that nanomaterials
society, treatments maywithbring
thesetoman-made
the society,materials
treatments
with thesea man-made
possess materials
health risks that must bepossess a health
minimized risks that must
by precautionary be minimized
principles wheneverby precautionary
these materials
principles whenever these materials are developed,
are developed, tested and then clinically applied. tested and then clinically applied.

Author
Author Contributions:
Contributions: J.S.J.S. is responsible
is responsible for supervision,
for supervision, review
review and editing
and editing of theand
of the paper paper and acquisition,
funding funding
acquisition, J.P. and M.K. prepared the original draft of the paper, T.H. contributed to visualization of schemes,
J.P. and M.K. prepared the original draft of the paper, T.H. contributed to visualization of schemes, V.Š. contributed
V.S. contributed
to data to data
validation and finalvalidation andauthors
review. All final review.
have read and agreed to the published version of the manuscript.
Int. J. Mol. Sci. 2020, 21, 2521 20 of 29

Funding: This research was funded by the Czech Science Foundation, Grant Number 17-10907S.
Acknowledgments: Authors are thankful to Adéla Siegelová for technical assistance.
Conflicts of Interest: The authors declare no conflict of interest.

References
1. Staszek, M.; Siegel, J.; Rimpelova, S.; Lyutakov, O.; Svorcik, V. Cytotoxicity of noble metal nanoparticles
sputtered into glycerol. Mater. Lett. 2015, 158, 351–354. [CrossRef]
2. Polivkova, M.; Valova, M.; Rimpelova, S.; Slepicka, P.; Svorcik, V.; Siegel, J. Pd nanowire coatings
of laser-treated polyethylene naphthalate: Preparation, characterization and biological response.
Express Polym. Lett. 2018, 12, 1039–1046. [CrossRef]
3. Siegel, J.; Polivkova, M.; Staszek, M.; Kolarova, K.; Rimpelova, S.; Svorcik, V. Nanostructured silver coatings
on polyimide and their antibacterial response. Mater. Lett. 2015, 145, 87–90. [CrossRef]
4. Fathi-Achachelouei, M.; Knopf-Marques, H.; Ribeiro da Silva, C.E.; Barthès, J.; Bat, E.; Tezcaner, A.; Vrana, N.E.
Use of nanoparticles in tissue engineering and regenerative medicine. Front. Bioeng. Biotechnol. 2019, 7, 113.
[CrossRef] [PubMed]
5. Yang, Y.; Wang, S.; Wang, Y.; Wang, X.; Wang, Q.; Chen, M. Advances in self-assembled chitosan nanomaterials
for drug delivery. Biotechnol. Adv. 2014, 32, 1301–1316. [CrossRef] [PubMed]
6. Bhunia, S.K.; Saha, A.; Maity, A.R.; Ray, S.C.; Jana, N.R. Carbon nanoparticle-based fluorescent bioimaging
probes. Sci. Rep. 2013, 3, 1473. [CrossRef] [PubMed]
7. Keles, E.; Song, Y.; Du, D.; Dong, W.-J.; Lin, Y. Recent progress in nanomaterials for gene delivery applications.
Biomater. Sci. 2016, 4, 1291–1309. [CrossRef]
8. Almeida, A.J.; Souto, E. Solid lipid nanoparticles as a drug delivery system for peptides and proteins.
Adv. Drug Deliv. Rev. 2007, 59, 478–490. [CrossRef]
9. Prego, C.; García, M.; Torres, D.; Alonso, M.J. Transmucosal macromolecular drug delivery. J. Control. Release
2005, 101, 151–162. [CrossRef]
10. Xu, Z.P.; Zeng, Q.H.; Lu, G.Q.; Yu, A.B. Inorganic nanoparticles as carriers for efficient cellular delivery.
Chem. Eng. Sci. 2006, 61, 1027–1040. [CrossRef]
11. Jean-Gilles, R.; Soscia, D.; Sequeira, S.; Melfi, M.; Gadre, A.; Castracane, J.; Larsen, M. Novel modeling
approach to generate a polymeric nanofiber scaffold for salivary gland cells. J. Nanotechnol. Eng. Med. 2010,
1, 031008. [CrossRef] [PubMed]
12. Li, X.; Liu, W.; Sun, L.; Fan, Y.; Feng, Q. The application of inorganic nanomaterials in bone tissue engineering.
J. Biomater. Tiss. Eng. 2014, 4, 994–1003. [CrossRef]
13. Sridhar, R.; Sundarrajan, S.; Venugopal, J.R.; Ravichandran, R.; Ramakrishna, S. Electrospun inorganic and
polymer composite nanofibers for biomedical applications. J. Biomater. Sci. Polym. Ed. 2013, 24, 365–385.
[CrossRef] [PubMed]
14. O’Brien, F.J. Biomaterials & scaffolds for tissue engineering. Mater. Today 2011, 14, 88–95.
15. Rezwan, K.; Chen, Q.Z.; Blaker, J.J.; Boccaccini, A.R. Biodegradable and bioactive porous polymer/inorganic
composite scaffolds for bone tissue engineering. Biomaterials 2006, 27, 3413–3431. [CrossRef]
16. Cao, L.; Wu, X.; Wang, Q.; Wang, J. Biocompatible nanocomposite of TiO2 incorporated bi-polymer for
articular cartilage tissue regeneration: A facile material. J. Photoch. Photobio. B 2018, 178, 440–446. [CrossRef]
17. Sahoo, N.G.; Pan, Y.Z.; Li, L.; He, C.B. Nanocomposites for bone tissue regeneration. Nanomedicine 2013, 8,
639–653. [CrossRef]
18. Baranes, K.; Shevach, M.; Shefi, O.; Dvir, T. Gold nanoparticle-decorated scaffolds promote neuronal
differentiation and maturation. Nano Lett. 2016, 16, 2916–2920. [CrossRef]
19. Dvir, T.; Timko, B.P.; Brigham, M.D.; Naik, S.R.; Karajanagi, S.S.; Levy, O.; Jin, H.; Parker, K.K.; Langer, R.;
Kohane, D.S. Nanowired three-dimensional cardiac patches. Nat. Nanotechnol. 2011, 6, 720–725. [CrossRef]
20. Jin, G.; Prabhakaran, M.P.; Nadappuram, B.P.; Singh, G.; Kai, D.; Ramakrishna, S. Electrospun poly(L-lactic
acid)-co-poly(-caprolactone) nanofibres containing silver nanoparticles for skin-tissue engineering.
J. Biomater. Sci. Polym. Ed. 2012, 23, 2337–2352.
21. Wei, G.; Ma, P.X. Structure and properties of nano-hydroxyapatite/polymer composite scaffolds for bone
tissue engineering. Biomaterials 2004, 25, 4749–4757. [CrossRef] [PubMed]
Int. J. Mol. Sci. 2020, 21, 2521 21 of 29

22. Bini, T.B.; Gao, S.; Wang, S.; Ramakrishna, S. Poly(l-lactide-co-glycolide) biodegradable microfibers and
electrospun nanofibers for nerve tissue engineering: An in vitro study. J. Mater. Sci. 2006, 41, 6453–6459.
[CrossRef]
23. Chen, X.; Fu, X.; Shi, J.-G.; Wang, H. Regulation of the osteogenesis of pre-osteoblasts by spatial arrangement
of electrospun nanofibers in two- and three-dimensional environments. Nanomed. Nanotechnol. Biol. Med.
2013, 9, 1283–1292. [CrossRef] [PubMed]
24. Teh, T.K.H.; Toh, S.-L.; Goh, J.C.H. Aligned hybrid silk scaffold for enhanced differentiation of mesenchymal
stem cells into ligament fibroblasts. Tissue Eng. C 2011, 17, 687–703. [CrossRef]
25. Wang, W.; Itoh, S.; Konno, K.; Kikkawa, T.; Ichinose, S.; Sakai, K.; Ohkuma, T.; Watabe, K. Effects of Schwann
cell alignment along the oriented electrospun chitosan nanofibers on nerve regeneration. J. Biomed. Mater.
Res. A 2009, 91, 994–1005. [CrossRef]
26. Cooper, A.; Jana, S.; Bhattarai, N.; Zhang, M. Aligned chitosan-based nanofibers for enhanced myogenesis.
J. Mater. Chem. 2010, 20, 8904–8911. [CrossRef]
27. Gautam, S.; Chou, C.-F.; Dinda, A.K.; Potdar, P.D.; Mishra, N.C. Surface modification of nanofibrous
polycaprolactone/gelatin composite scaffold by collagen type I grafting for skin tissue engineering. Mater. Sci.
Eng. C 2014, 34, 402–409. [CrossRef]
28. Li, W.-J.; Tuli, R.; Okafor, C.; Derfoul, A.; Danielson, K.G.; Hall, D.J.; Tuan, R.S. A three-dimensional
nanofibrous scaffold for cartilage tissue engineering using human mesenchymal stem cells. Biomaterials 2005,
26, 599–609. [CrossRef]
29. Frenkel, S.R.; Di Cesare, P.E. Scaffolds for articular cartilage repair. Ann. Biomed. Eng. 2004, 32, 26–34.
[CrossRef]
30. Woodfield, T.; Bezemer, J.; Pieper, J.; Van Blitterswijk, C.; Riesle, J. Scaffolds for tissue engineering of cartilage.
Crit. Rev. Eukaryot. Gene Expr. 2002, 12, 28. [CrossRef]
31. Wang, Y.; Blasioli, D.J.; Kim, H.-J.; Kim, H.S.; Kaplan, D.L. Cartilage tissue engineering with silk scaffolds
and human articular chondrocytes. Biomaterials 2006, 27, 4434–4442. [CrossRef] [PubMed]
32. Griffon, D.J.; Sedighi, M.R.; Schaeffer, D.V.; Eurell, J.A.; Johnson, A.L. Chitosan scaffolds: Interconnective
pore size and cartilage engineering. Acta Biomater. 2006, 2, 313–320. [CrossRef] [PubMed]
33. Yoo, H.S.; Lee, E.A.; Yoon, J.J.; Park, T.G. Hyaluronic acid modified biodegradable scaffolds for cartilage
tissue engineering. Biomaterials 2005, 26, 1925–1933. [CrossRef] [PubMed]
34. Chang, K.Y.; Hung, L.H.; Chu, I.M.; Ko, C.S.; Lee, Y.D. The application of type II collagen and chondroitin
sulfate grafted PCL porous scaffold in cartilage tissue engineering. J. Biomed. Mater. Res. A 2010, 92, 712–723.
[CrossRef] [PubMed]
35. Wang, C.-C.; Yang, K.-C.; Lin, K.-H.; Liu, H.-C.; Lin, F.-H. A highly organized three-dimensional alginate
scaffold for cartilage tissue engineering prepared by microfluidic technology. Biomaterials 2011, 32, 7118–7126.
[CrossRef]
36. Lien, S.-M.; Ko, L.-Y.; Huang, T.-J. Effect of pore size on ECM secretion and cell growth in gelatin scaffold for
articular cartilage tissue engineering. Acta Biomater. 2009, 5, 670–679. [CrossRef]
37. Müller, F.A.; Müller, L.; Hofmann, I.; Greil, P.; Wenzel, M.M.; Staudenmaier, R. Cellulose-based scaffold
materials for cartilage tissue engineering. Biomaterials 2006, 27, 3955–3963. [CrossRef]
38. Svensson, A.; Nicklasson, E.; Harrah, T.; Panilaitis, B.; Kaplan, D.; Brittberg, M.; Gatenholm, P. Bacterial
cellulose as a potential scaffold for tissue engineering of cartilage. Biomaterials 2005, 26, 419–431. [CrossRef]
39. Bölgen, N.; Yang, Y.; Korkusuz, P.; Güzel, E.; El Haj, A.J.; Pişkin, E. 3D ingrowth of bovine articular
chondrocytes in biodegradable cryogel scaffolds for cartilage tissue engineering. J. Tissue Eng. Regen. Med.
2011, 5, 770–779. [CrossRef]
40. Chu, C.R.; Coutts, R.D.; Yoshioka, M.; Harwood, F.L.; Monosov, A.Z.; Amiel, D. Articular cartilage repair
using allogeneic perichondrocyteseeded biodegradable porous polylactic acid (PLA): A tissue-engineering
study. J. Biomed. Mater. Res. 1995, 29, 1147–1154. [CrossRef]
41. Moran, J.M.; Pazzano, D.; Bonassar, L.J. Characterization of polylactic acid–polyglycolic acid composites for
cartilage tissue engineering. Tissue Eng. 2003, 9, 63–70. [CrossRef] [PubMed]
42. Sato, M.; Ishihara, M.; Ishihara, M.; Kaneshiro, N.; Mitani, G.; Nagai, T.; Kutsuna, T.; Asazuma, T.; Kikuchi, M.;
Mochida, J. Effects of growth factors on heparin-carrying polystyrene-coated atelocollagen scaffold for
articular cartilage tissue engineering. J. Biomed. Mater. Res. B 2007, 83, 181–188. [CrossRef] [PubMed]
Int. J. Mol. Sci. 2020, 21, 2521 22 of 29

43. Springer, I.N.; Fleiner, B.; Jepsen, S.; Açil, Y. Culture of cells gained from temporomandibular joint cartilage
on non-absorbable scaffolds. Biomaterials 2001, 22, 2569–2577. [CrossRef]
44. Neves, A.A.; Medcalf, N.; Brindle, K.M. Influence of stirring-induced mixing on cell proliferation and
extracellular matrix deposition in meniscal cartilage constructs based on polyethylene terephthalate scaffolds.
Biomaterials 2005, 26, 4828–4836. [CrossRef]
45. Vikingsson, L.; Gómez-Tejedor, J.A.; Ferrer, G.G.; Ribelles, J.G. An experimental fatigue study of a porous
scaffold for the regeneration of articular cartilage. J. Biomech. 2015, 48, 1310–1317. [CrossRef]
46. Ohyabu, Y.; Adegawa, T.; Yoshioka, T.; Ikoma, T.; Uemura, T.; Tanaka, J. Cartilage regeneration using a
porous scaffold, a collagen sponge incorporating a hydroxyapatite/chondroitinsulfate composite. Mater. Sci.
Eng. B 2010, 173, 204–207. [CrossRef]
47. Kao, C.-T.; Lin, C.-C.; Chen, Y.-W.; Yeh, C.-H.; Fang, H.-Y.; Shie, M.-Y. Poly(dopamine) coating of 3D printed
poly(lactic acid) scaffolds for bone tissue engineering. Mater. Sci. Eng. C 2015, 56, 165–173. [CrossRef]
[PubMed]
48. Liu, H.; Slamovich, E.; Webster, T. Less harmful acidic degradation of poly(lactic-co-glycolic acid) bone tissue
engineering scaffolds through titania nanoparticle addition. Int. J. Nanomed. 2006, 1, 541–545. [CrossRef]
49. Kim, J.; Kim, I.S.; Cho, T.H.; Lee, K.B.; Hwang, S.J.; Tae, G.; Noh, I.; Lee, S.H.; Park, Y.; Sun, K. Bone regeneration
using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem
cells. Biomaterials 2007, 28, 1830–1837. [CrossRef]
50. Shuai, C.; Mao, Z.; Lu, H.; Nie, Y.; Hu, H.; Peng, S. Fabrication of porous polyvinyl alcohol scaffold for bone
tissue engineering via selective laser sintering. Biofabrication 2013, 5, 015014. [CrossRef]
51. Lu, M.-C.; Huang, Y.-T.; Lin, J.-H.; Yao, C.-H.; Lou, C.-W.; Tsai, C.-C.; Chen, Y.-S. Evaluation of a multi-layer
microbraided polylactic acid fiber-reinforced conduit for peripheral nerve regeneration. J. Mater. Sci.
Mater. Med. 2009, 20, 1175–1180. [CrossRef] [PubMed]
52. Lavik, E.; Teng, Y.D.; Snyder, E.; Langer, R. Seeding neural stem cells on scaffolds of PGA, PLA, and their
copolymers. Methods Mol. Biol. 2002, 198, 89–97. [PubMed]
53. Leipzig, N.D.; Wylie, R.G.; Kim, H.; Shoichet, M.S. Differentiation of neural stem cells in three-dimensional
growth factor-immobilized chitosan hydrogel scaffolds. Biomaterials 2011, 32, 57–64. [CrossRef] [PubMed]
54. Chen, Y.W.; Chiou, S.H.; Wong, T.T.; Ku, H.H.; Lin, H.T.; Chung, C.F.; Yen, S.H.; Kao, C.L. Using gelatin
scaffold with coated basic fibroblast growth factor as a transfer system for transplantation of human neural
stem cells. Transplant. Proc. 2006, 38, 1616–1617. [CrossRef] [PubMed]
55. Nistal, F.; García-Martínez, V.; Arbe, E.; Fernández, D.; Artiñano, E.; Mazorra, F.; Gallo, I. In vivo experimental
assessment of polytetrafluoroethylene trileaflet heart valve prosthesis. J. Thorac. Cardiovasc. Surg. 1990, 99,
1074–1081. [PubMed]
56. Stock, U.; Mayer, J.E., Jr. Tissue engineering of cardiac valves on the basis of PGA/PLA Co-polymers. J. Long
Term Eff. Med. Implants 2001, 11, 249–260. [CrossRef]
57. Balguid, A.; Mol, A.; van Marion, M.H.; Bank, R.A.; Bouten, C.V.C.; Baaijens, F.P.T. Tailoring fiber diameter in
electrospun poly(ε-caprolactone) scaffolds for optimal cellular infiltration in cardiovascular tissue engineering.
Tissue Eng. A 2008, 15, 437–444. [CrossRef]
58. Castellano, D.; Blanes, M.; Marco, B.; Cerrada, I.; Ruiz-Saurí, A.; Pelacho, B.; Araña, M.; Montero, J.A.;
Cambra, V.; Prosper, F.; et al. A comparison of electrospun polymers reveals poly(3-hydroxybutyrate) fiber
as a superior scaffold for cardiac repair. Stem Cells Dev. 2014, 23, 1479–1490. [CrossRef]
59. Chun, S.; Huang, Y.; Xie, W.J.; Hou, Y.; Huang, R.P.; Song, Y.M.; Liu, X.M.; Zheng, W.; Shi, Y.; Song, C.F.
Adhesive growth of pancreatic islet cells on a polyglycolic acid fibrous scaffold. Transplant. Proc. 2008, 40,
1658–1663. [CrossRef]
60. Elcin, Y.M.; Elcin, E.; Bretzel, R.; Linn, T. Pancreatic islet culture and transplantation using chitosan and
PLGA scaffolds. Adv. Exp. Med. Biol. 2003, 534, 255–264.
61. Muthyala, S.; Bhonde, R.R.; Nair, P.D. Cytocompatibility studies of mouse pancreatic islets on gelatin—PVP
semi IPN scaffolds in vitro: Potential implication towards pancreatic tissue engineering. Islets 2010, 2,
357–366. [CrossRef]
62. Teramura, Y.; Kaneda, Y.; Iwata, H. Islet-encapsulation in ultra-thin layer-by-layer membranes of poly(vinyl
alcohol) anchored to poly(ethylene glycol)–lipids in the cell membrane. Biomaterials 2007, 28, 4818–4825.
[CrossRef]
Int. J. Mol. Sci. 2020, 21, 2521 23 of 29

63. Pattison, M.A.; Wurster, S.; Webster, T.J.; Haberstroh, K.M. Three-dimensional, nano-structured PLGA
scaffolds for bladder tissue replacement applications. Biomaterials 2005, 26, 2491–2500. [CrossRef] [PubMed]
64. Brown, A.L.; Srokowski, E.M.; Shu, X.Z.; Prestwich, G.D.; Woodhouse, K.A. Development of a model
bladder extracellular matrix combining disulfide cross-linked hyaluronan with decellularized bladder tissue.
Macromol. Biosci. 2006, 6, 648–657. [CrossRef] [PubMed]
65. Jang, Y.-J.; Chun, S.Y.; Kim, G.N.; Kim, J.R.; Oh, S.H.; Lee, J.H.; Kim, B.S.; Song, P.H.; Yoo, E.S.;
Kwon, T.G. Characterization of a novel composite scaffold consisting of acellular bladder submucosa
matrix, polycaprolactone and Pluronic F127 as a substance for bladder reconstruction. Acta Biomater. 2014,
10, 3117–3125. [CrossRef] [PubMed]
66. Tsang, M.; Chun, Y.W.; Im, Y.M.; Khang, D.; Webster, T.J. Effects of increasing carbon nanofiber density in
polyurethane composites for inhibiting bladder cancer cell functions. Tissue Eng. A 2011, 17, 1879–1889.
[CrossRef]
67. Espandar, L.; Bunnell, B.; Wang, G.Y.; Gregory, P.; McBride, C.; Moshirfar, M. Adipose-derived stem cells
on hyaluronic acid-derived scaffold: A new horizon in bioengineered cornea. Arch. Ophthalmol. 2012, 130,
202–208. [CrossRef]
68. Liang, Y.; Liu, W.; Han, B.; Yang, C.; Ma, Q.; Zhao, W.; Rong, M.; Li, H. Fabrication and characters of a corneal
endothelial cells scaffold based on chitosan. J. Mater. Sci. Mater. Med. 2011, 22, 175–183. [CrossRef]
69. Uchino, Y.; Shimmura, S.; Miyashita, H.; Taguchi, T.; Kobayashi, H.; Shimazaki, J.; Tanaka, J.; Tsubota, K.
Amniotic membrane immobilized poly(vinyl alcohol) hybrid polymer as an artificial cornea scaffold that
supports a stratified and differentiated corneal epithelium. J. Biomed. Mater. Res. B 2007, 81, 201–206.
[CrossRef]
70. Ozcelik, B.; Brown, K.D.; Blencowe, A.; Daniell, M.; Stevens, G.W.; Qiao, G.G. Ultrathin chitosan–poly(ethylene
glycol) hydrogel films for corneal tissue engineering. Acta Biomater. 2013, 9, 6594–6605. [CrossRef]
71. Sun, T.; Mai, S.; Norton, D.; Haycock, J.W.; Ryan, A.J.; Macneil, S. Self-organization of skin cells in
three-dimensional electrospun polystyrene scaffolds. Tissue Eng. 2005, 11, 1023–1033. [CrossRef] [PubMed]
72. Yang, J.; Shi, G.; Bei, J.; Wang, S.; Cao, Y.; Shang, Q.; Yang, G.; Wang, W. Fabrication and surface modification
of macroporous poly(L-lactic acid) and poly(L-lactic-co-glycolic acid) (70/30) cell scaffolds for human skin
fibroblast cell culture. J. Biomed. Mater. Res. 2002, 62, 438–446. [CrossRef] [PubMed]
73. Adekogbe, I.; Ghanem, A. Fabrication and characterization of DTBP-crosslinked chitosan scaffolds for skin
tissue engineering. Biomaterials 2005, 26, 7241–7250. [CrossRef] [PubMed]
74. Lee, S.B.; Kim, Y.H.; Chong, M.S.; Hong, S.H.; Lee, Y.M. Study of gelatin-containing artificial skin V:
Fabrication of gelatin scaffolds using a salt-leaching method. Biomaterials 2005, 26, 1961–1968. [CrossRef]
75. Chang, C.-H.; Liu, H.-C.; Lin, C.-C.; Chou, C.-H.; Lin, F.-H. Gelatin-chondroitin-hyaluronan tri-copolymer
scaffold for cartilage tissue engineering. Biomaterials 2003, 24, 4853–4858. [CrossRef]
76. Janouskova, O. Synthetic polymer scaffolds for soft tissue engineering. Physiol. Res. 2018, 67, 335–348.
[CrossRef]
77. Polivkova, M.; Strublova, V.; Hubacek, T.; Rimpelova, S.; Svorcik, V.; Siegel, J. Surface characterization
and antibacterial response of silver nanowire arrays supported on laser-treated polyethylene naphthalate.
Mater. Sci. Eng. C 2017, 72, 512–518. [CrossRef]
78. Siegel, J.; Lyutakov, O.; Polivkova, M.; Staszek, M.; Hubacek, T.; Svorcik, V. Laser-assisted immobilization of
colloid silver nanoparticles on polyethyleneterephthalate. Appl. Surf. Sci. 2017, 420, 661–668. [CrossRef]
79. Siegel, J.; Sulakova, P.; Kaimlova, M.; Svorcik, V.; Hubacek, T. Underwater laser treatment of PET: Effect of
processing parameters on surface morphology and chemistry. Appl. Sci. 2018, 8, 2389–2397. [CrossRef]
80. Kaimlova, M.; Nemogova, I.; Kolarova, K.; Slepicka, P.; Svorcik, V.; Siegel, J. Optimization of silver nanowire
formation on laser processed PEN: Surface properties and antibacterial effects. Appl. Surf. Sci. 2019, 473,
516–526. [CrossRef]
81. Peterbauer, T.; Yakunin, S.; Siegel, J.; Heitz, J. Dynamics of the Alignment of Mammalian Cells on a
Nano-Structured Polymer Surface. Macromol. Symp. 2010, 296, 272–277. [CrossRef]
82. Zhao, H.; Ding, R.; Zhao, X.; Li, Y.; Qu, L.; Pei, H.; Yildirimer, L.; Wu, Z.; Zhang, W. Graphene-based
nanomaterials for drug and/or gene delivery, bioimaging, and tissue engineering. Drug Discov. Today 2017,
22, 1302–1317. [CrossRef] [PubMed]
Int. J. Mol. Sci. 2020, 21, 2521 24 of 29

83. Farzin, L.; Shamsipur, M.; Samandari, L.; Sheibani, S. Advances in the design of nanomaterial-based
electrochemical affinity and enzymatic biosensors for metabolic biomarkers: A review. Microchim. Acta 2018,
185, 276. [CrossRef] [PubMed]
84. Mahaye, N.; Thwala, M.; Cowan, D.A.; Musee, N. Genotoxicity of metal based engineered nanoparticles in
aquatic organisms: A review. Mutat. Res. Rev. Mutat. Res. 2017, 773, 134–160. [CrossRef]
85. Hillman, Y.; Lustiger, D.; Wine, Y. Antibody-based nanotechnology. Nanotechnology 2019, 30, 282001.
[CrossRef]
86. Slowing, I.I.; Vivero-Escoto, J.L.; Wu, C.-W.; Lin, V.S.Y. Mesoporous silica nanoparticles as controlled release
drug delivery and gene transfection carriers. Adv. Drug Deliv. Rev. 2008, 60, 1278–1288. [CrossRef]
87. Tang, Y.; Zhao, Y.; Wang, X.; Lin, T. Layer-by-layer assembly of silica nanoparticles on 3D fibrous scaffolds:
Enhancement of osteoblast cell adhesion, proliferation, and differentiation. J. Biomed. Mater. Res. A 2014, 102,
3803–3812. [CrossRef]
88. Lipski, A.M.; Pino, C.J.; Haselton, F.R.; Chen, I.W.; Shastri, V.P. The effect of silica nanoparticle-modified
surfaces on cell morphology, cytoskeletal organization and function. Biomaterials 2008, 29, 3836–3846.
[CrossRef]
89. Wu, X.; Wu, M.; Zhao, J.X. Recent development of silica nanoparticles as delivery vectors for cancer imaging
and therapy. Nanomed. Nanotechnol. Biol. Med. 2014, 10, 297–312. [CrossRef]
90. Lee, J.M.; Kim, B.-S.; Lee, H.; Im, G.-I. In vivo tracking of mesechymal stem cells using fluorescent
nanoparticles in an osteochondral repair model. Mol. Ther. 2012, 20, 1434–1442. [CrossRef]
91. Yang, K.-N.; Zhang, C.-Q.; Wang, W.; Wang, P.C.; Zhou, J.-P.; Liang, X.-J. pH-responsive mesoporous silica
nanoparticles employed in controlled drug delivery systems for cancer treatment. Cancer Biol. Med. 2014, 11,
34–43. [PubMed]
92. Arjmandi, M.; Ramezani, M. Mechanical and tribological assessment of silica
nanoparticle-alginate-polyacrylamide nanocomposite hydrogels as a cartilage replacement. J. Mech. Behav.
Biomed. Mater. 2019, 95, 196–204. [CrossRef] [PubMed]
93. Beck, G.R., Jr.; Ha, S.W.; Camalier, C.E.; Yamaguchi, M.; Li, Y.; Lee, J.K.; Weitzmann, M.N. Bioactive
silica-based nanoparticles stimulate bone-forming osteoblasts, suppress bone-resorbing osteoclasts, and
enhance bone mineral density in vivo. Nanomed. Nanotechnol. Biol. Med. 2012, 8, 793–803. [CrossRef]
[PubMed]
94. Baei, P.; Jalili-Firoozinezhad, S.; Rajabi-Zeleti, S.; Tafazzoli-Shadpour, M.; Baharvand, H.; Aghdami, N.
Electrically conductive gold nanoparticle-chitosan thermosensitive hydrogels for cardiac tissue engineering.
Mater. Sci. Eng. C 2016, 63, 131–141. [CrossRef]
95. Suh, K.S.; Lee, Y.S.; Seo, S.H.; Kim, Y.S.; Choi, E.M. Gold nanoparticles attenuates antimycin a-induced
mitochondrial dysfunction in MC3T3-E1 osteoblastic cells. Biol. Trace Elem. Res. 2013, 153, 428–436.
[CrossRef]
96. Asgari, V.; Landarani-Isfahani, A.; Salehi, H.; Amirpour, N.; Hashemibeni, B.; Rezaei, S.; Bahramian, H. The
story of nanoparticles in differentiation of stem cells into neural cells. Neurochem. Res. 2019, 44, 2695–2707.
[CrossRef]
97. You, J.-O.; Rafat, M.; Ye, G.J.C.; Auguste, D.T. Nanoengineering the heart: Conductive scaffolds enhance
connexin 43 expression. Nano Lett. 2011, 11, 3643–3648. [CrossRef]
98. Aktürk, Ö.; Keskin, D. Collagen/PEO/gold nanofibrous matrices for skin tissue engineering. Turk. J. Biol.
2016, 40, 380–398. [CrossRef]
99. Xing, Z.-C.; Chae, W.-P.; Baek, J.-Y.; Choi, M.-J.; Jung, Y.; Kang, I.-K. In Vitro Assessment of antibacterial
activity and cytocompatibility of silver-containing PHBV nanofibrous scaffolds for tissue engineering.
Biomacromolecules 2010, 11, 1248–1253. [CrossRef]
100. Patrascu, J.M.; Nedelcu, I.A.; Sonmez, M.; Ficai, D.; Ficai, A.; Vasile, B.S.; Ungureanu, C.; Albu, M.G.;
Andor, B.; Andronescu, E.; et al. Composite scaffolds based on silver nanoparticles for biomedical
applications. J. Nanomater. 2015, 2015, 587989. [CrossRef]
101. Johari, N.; Hosseini, H.R.M.; Samadikuchaksaraei, A. Mechanical modeling of silk fibroin/tio2 and silk
fibroin/fluoridated tio2 nanocomposite scaffolds for bone tissue engineering. Iran. Polym. J. 2020, 29, 219–224.
[CrossRef]
Int. J. Mol. Sci. 2020, 21, 2521 25 of 29

102. Carballo-Vila, M.; Moreno-Burriel, B.; Chinarro, E.; Jurado, J.R.; Casañ-Pastor, N.; Collazos-Castro, J.E.
Titanium oxide as substrate for neural cell growth. J. Biomed. Mater. Res. A 2009, 90, 94–105. [CrossRef]
[PubMed]
103. Jawad, H.; Ali, N.N.; Lyon, A.R.; Chen, Q.Z.; Harding, S.E.; Boccaccini, A.R. Myocardial tissue engineering:
A review. J. Tissue Eng. Regen. Med. 2007, 1, 327–342. [CrossRef] [PubMed]
104. Li, N.; Fan, X.; Tang, K.; Zheng, X.; Liu, J.; Wang, B. Nanocomposite scaffold with enhanced stability by
hydrogen bonds between collagen, polyvinyl pyrrolidone and titanium dioxide. Colloids Surf. B 2016, 140,
287–296. [CrossRef]
105. Zhang, N.; Lock, J.; Sallee, A.; Liu, H. Magnetic nanocomposite hydrogel for potential cartilage tissue
engineering: Synthesis, characterization, and cytocompatibility with bone marrow derived mesenchymal
stem cells. ACS Appl. Mater. Interfaces 2015, 7, 20987–20998. [CrossRef]
106. Bock, N.; Riminucci, A.; Dionigi, C.; Russo, A.; Tampieri, A.; Landi, E.; Goranov, V.A.; Marcacci, M.; Dediu, V.
A novel route in bone tissue engineering: Magnetic biomimetic scaffolds. Acta Biomater. 2010, 6, 786–796.
[CrossRef]
107. Poggetti, A.; Battistini, P.; Parchi, P.D.; Novelli, M.; Raffa, S.; Cecchini, M.; Nucci, A.M.; Lisanti, M. How
to direct the neuronal growth process in peripheral nerve regeneration: Future strategies for nanosurfaces
scaffold and magnetic nanoparticles. Surg. Technol. Int. 2017, 30, 458–461.
108. Shimizu, K.; Ito, A.; Lee, J.-K.; Yoshida, T.; Miwa, K.; Ishiguro, H.; Numaguchi, Y.; Murohara, T.; Kodama, I.;
Honda, H. Construction of multi-layered cardiomyocyte sheets using magnetite nanoparticles and magnetic
force. Biotechnol. Bioeng. 2007, 96, 803–809. [CrossRef]
109. Shao, C.; Chen, J.; Chen, P.; Zhu, M.; Yao, Q.; Gu, P.; Fu, Y.; Fan, X. Targeted transplantation of human
umbilical cord blood endothelial progenitor cells with immunomagnetic nanoparticles to repair corneal
endothelium defect. Stem Cells Dev. 2014, 24, 756–767. [CrossRef]
110. Kay, S.; Thapa, A.; Haberstroh, K.M.; Webster, T.J. Nanostructured polymer/nanophase ceramic composites
enhance osteoblast and chondrocyte adhesion. Tissue Eng. 2002, 8, 753–761. [CrossRef]
111. Li, X.; Feng, Q.; Liu, X.; Dong, W.; Cui, F. Collagen-based implants reinforced by chitin fibres in a goat shank
bone defect model. Biomaterials 2006, 27, 1917–1923. [CrossRef] [PubMed]
112. Barabadi, Z.; Azami, M.; Sharifi, E.; Karimi, R.; Lotfibakhshaiesh, N.; Roozafzoon, R.; Joghataei, M.T.;
Ai, J. Fabrication of hydrogel based nanocomposite scaffold containing bioactive glass nanoparticles for
myocardial tissue engineering. Mater. Sci. Eng. C 2016, 69, 1137–1146. [CrossRef] [PubMed]
113. Karbasi, S.; Alizadeh, Z.M. Effects of multi-wall carbon nanotubes on structural and mechanical properties
of poly(3-hydroxybutyrate)/chitosan electrospun scaffolds for cartilage tissue engineering. Bull. Mater. Sci.
2017, 40, 1247–1253. [CrossRef]
114. Shi, X.; Sitharaman, B.; Pham, Q.P.; Liang, F.; Wu, K.; Edward Billups, W.; Wilson, L.J.; Mikos, A.G. Fabrication
of porous ultra-short single-walled carbon nanotube nanocomposite scaffolds for bone tissue engineering.
Biomaterials 2007, 28, 4078–4090. [CrossRef]
115. Lee, J.-R.; Ryu, S.; Kim, S.; Kim, B.-S. Behaviors of stem cells on carbon nanotube. Biomater. Res. 2015, 19, 3.
[CrossRef]
116. Stout, D.A.; Basu, B.; Webster, T.J. Poly(lactic–co-glycolic acid): Carbon nanofiber composites for myocardial
tissue engineering applications. Acta Biomater. 2011, 7, 3101–3112. [CrossRef]
117. Jing, T.; Shao, Y.; Zheng, Y.; Tian, J. Graphene oxide-based Fe3 O4 nanoparticles as a novel scaffold for the
immobilization of porcine pancreatic lipase. RSC Adv. 2015, 5, 103943–103955.
118. Orlando, A.; Colombo, M.; Prosperi, D.; Corsi, F.; Panariti, A.; Rivolta, I.; Masserini, M.; Cazzaniga, E.
Evaluation of gold nanoparticles biocompatibility: A multiparametric study on cultured endothelial cells
and macrophages. J. Nanopart. Res. 2016, 18, 58. [CrossRef]
119. Polivkova, M.; Hubacek, T.; Staszek, M.; Svorcik, V.; Siegel, J. Antimicrobial treatment of polymeric medical
devices by silver nanomaterials and related technology. Int. J. Mol. Sci. 2017, 18, 419. [CrossRef]
120. Gunawidjaja, R.; Kharlampieva, E.; Choi, I.; Tsukruk, V. Bimetallic nanostructures as active raman markers:
Gold-nanoparticle assembly on 1D and 2D silver nanostructure surfaces. Small 2009, 5, 2460–2466. [CrossRef]
121. Polivkova, M.; Siegel, J.; Rimpelova, S.; Hubacek, T.; Kolska, Z.; Svorcik, V. Cytotoxicity of Pd nanostructures
supported on PEN: Influence of sterilization on Pd/PEN interface. Mater. Sci. Eng. C 2017, 70, 479–486.
[CrossRef] [PubMed]
Int. J. Mol. Sci. 2020, 21, 2521 26 of 29

122. Siegel, J.; Polivkova, M.; Kasalkova, N.S.; Kolska, Z.; Svorcik, V. Properties of silver nanostructure-coated
PTFE and its biocompatibility. Nanoscale Res. Lett. 2013, 8, 1–10. [CrossRef] [PubMed]
123. Siegel, J.; Zaruba, K.; Svorcik, V.; Kroumanova, K.; Burketova, L.; Martinec, J. Round-shape gold nanoparticles:
Effect of particle size and concentration on Arabidopsis thaliana root growth. Nanoscale Res. Lett. 2018, 13,
1–7. [CrossRef] [PubMed]
124. Buchman, J.T.; Hudson-Smith, N.V.; Landy, K.M.; Haynes, C.L. Understanding nanoparticle toxicity
mechanisms to inform redesign strategies to reduce environmental impact. Acc. Chem. Res. 2019, 52,
1632–1642. [CrossRef] [PubMed]
125. Jaroenworaluck, A.; Sunsaneeyametha, W.; Kosachan, N.; Stevens, R. Characteristics of silica-coated TiO2
and its UV absorption for sunscreen cosmetic applications. Surf. Interface Anal. 2006, 38, 473–477. [CrossRef]
126. Oguma, J.; Kakuma, Y.; Murayama, S.; Nosaka, Y. Effects of silica coating on photocatalytic reactions of
anatase titanium dioxide studied by quantitative detection of reactive oxygen species. Appl. Catal. B 2013,
129, 282–286. [CrossRef]
127. Chen, S.-Z.; Zhang, P.-Y.; Zhu, W.-P.; Chen, L.; Xu, S.-M. Deactivation of TiO2 photocatalytic films loaded on
aluminium: XPS and AFM analyses. Appl. Surf. Sci. 2006, 252, 7532–7538. [CrossRef]
128. Skocaj, M.; Filipic, M.; Petkovic, J.; Novak, S.J.R. Titanium dioxide in our everyday life; is it safe? Radiol. Oncol.
2011, 45, 227–247. [CrossRef]
129. Alexiou, C.; Schmid, R.; Jurgons, R.; Kremer, M.; Wanner, G.; Bergemann, C.; Huenges, E.; Nawroth, T.;
Arnold, W.; Parak, F. Targeting cancer cells: Magnetic nanoparticles as drug carriers. Eur. Biophys. J. 2006, 35,
446–450. [CrossRef]
130. Hergt, R.; Dutz, S.; Müller, R.; Zeisberger, M. Magnetic particle hyperthermia: Nanoparticle magnetism and
materials development for cancer therapy. J. Phys. Condens. Matter 2006, 18, 2919–2934. [CrossRef]
131. Park, H.; Park, H.-J.; Kim, J.A.; Lee, S.H.; Kim, J.H.; Yoon, J.; Park, T.H. Inactivation of Pseudomonas
aeruginosa PA01 biofilms by hyperthermia using superparamagnetic nanoparticles. J. Microbiol. Methods
2011, 84, 41–45. [CrossRef]
132. Cunningham, C.H.; Arai, T.; Yang, P.C.; McConnell, M.V.; Pauly, J.M.; Conolly, S.M. Positive contrast magnetic
resonance imaging of cells labeled with magnetic nanoparticles. Magn. Reson. Med. 2005, 53, 999–1005.
[CrossRef] [PubMed]
133. Stoimenov, P.K.; Klinger, R.L.; Marchin, G.L.; Klabunde, K.J. Metal oxide nanoparticles as bactericidal agents.
Langmuir 2002, 18, 6679–6686. [CrossRef]
134. Jones, N.; Ray, B.; Ranjit, K.T.; Manna, A.C. Antibacterial activity of ZnO nanoparticle suspensions on a
broad spectrum of microorganisms. FEMS Microbiol. Lett. 2008, 279, 71–76. [CrossRef] [PubMed]
135. Tran, P.A.; Webster, T.J. Selenium nanoparticles inhibit Staphylococcus aureus growth. Int. J. Nanomed. 2011,
6, 1553–1558.
136. Parkin, S.S.; Kaiser, C.; Panchula, A.; Rice, P.M.; Hughes, B.; Samant, M.; Yang, S.-H. Giant tunnelling
magnetoresistance at room temperature with MgO (100) tunnel barriers. Nat. Mater. 2004, 3, 862–867.
[CrossRef]
137. Singh, J.P.; Chae, K.H. d◦ ferromagnetism of magnesium oxide. Condens. Matter. 2017, 2, 36. [CrossRef]
138. Garcia, M.A.; Merino, J.M.; Fernández Pinel, E.; Quesada, A.; de la Venta, J.; Ruíz González, M.L.; Castro, G.R.;
Crespo, P.; Llopis, J.; González-Calbet, J.M.; et al. Magnetic properties of ZnO nanoparticles. Nano Lett. 2007,
7, 1489–1494. [CrossRef]
139. Bernard, G.M.; Eichele, K.; Wu, G.; Kirby, C.W.; Wasylishen, R.E. Nuclear magnetic shielding tensors for
the carbon, nitrogen, and selenium nuclei of selenocyanates—A combined experimental and theoretical
approach. Can. J. Chem. 2000, 78, 614–625. [CrossRef]
140. Aykut-Yetkiner, A.; Attin, T.; Wiegand, A. Prevention of dentine erosion by brushing with anti-erosive
toothpastes. J. Dent. 2014, 42, 856–861. [CrossRef]
141. Maeda, H.; Kasuga, T. Calcium phosphate cement with silicate ion releasing ability by incorporating calcium
silicate hydrate. J. Ceram. Soc. JPN 2014, 122, 591–595. [CrossRef]
142. Chatterjee, K.; Sun, L.; Chow, L.C.; Young, M.F.; Simon, C.G., Jr. Combinatorial screening of osteoblast
response to 3D calcium phosphate/poly(ε-caprolactone) scaffolds using gradients and arrays. Biomaterials
2011, 32, 1361–1369. [CrossRef] [PubMed]
143. Gohil, S.; Domb, A.; Kumar, N. Nanomaterials for regenerative medicine. Nanomedicine 2011, 6, 157–181.
Int. J. Mol. Sci. 2020, 21, 2521 27 of 29

144. Abdulkareem, E.H.; Memarzadeh, K.; Allaker, R.P.; Huang, J.; Pratten, J.; Spratt, D. Anti-biofilm activity of
zinc oxide and hydroxyapatite nanoparticles as dental implant coating materials. J. Dent. 2015, 43, 1462–1469.
[CrossRef]
145. Madhumathi, K.; Sampath Kumar, T.S. Regenerative potential and anti-bacterial activity of tetracycline
loaded apatitic nanocarriers for the treatment of periodontitis. Biomed. Mater. 2014, 9, 035002. [CrossRef]
146. Choi, B.; Cui, Z.-K.; Kim, S.; Fan, J.; Wu, B.M.; Lee, M. Glutamine-chitosan modified calcium phosphate
nanoparticles for efficient siRNA delivery and osteogenic differentiation. J. Mater. Chem. B 2015, 3, 6448–6455.
[CrossRef]
147. Eatemadi, A.; Daraee, H.; Karimkhanloo, H.; Kouhi, M.; Zarghami, N.; Akbarzadeh, A.; Abasi, M.;
Hanifehpour, Y.; Joo, S.W. Carbon nanotubes: Properties, synthesis, purification, and medical applications.
Nanoscale Res. Lett. 2014, 9, 393. [CrossRef]
148. Klumpp, C.; Kostarelos, K.; Prato, M.; Bianco, A. Functionalized carbon nanotubes as emerging nanovectors
for the delivery of therapeutics. Biochim. Biophys. Acta 2006, 1758, 404–412. [CrossRef]
149. Raja, I.S.; Song, S.J.; Kang, M.S.; Lee, Y.B.; Kim, B.; Hong, S.W.; Jeong, S.J.; Lee, J.C.; Han, D.W. Toxicity of
zero- and one-dimensional carbon nanomaterials. Nanomaterials 2019, 9, 1214. [CrossRef]
150. Zhu, Y.; Li, W. Cytotoxicity of carbon nanotubes. Sci. China Ser. B 2008, 51, 1021–1029. [CrossRef]
151. Xie, X.; Hu, K.; Fang, D.; Shang, L.; Tran, S.; Cerruti, M. Graphene and hydroxyapatite self-assemble
into homogenous, free standing nanocomposite hydrogels for bone tissue engineering. Nanoscale 2015, 7,
7992–8002. [CrossRef] [PubMed]
152. Lamprecht, C.; Taale, M.; Paulowicz, I.; Westerhaus, H.; Grabosch, C.; Schuchardt, A.; Mecklenburg, M.;
Böttner, M.; Lucius, R.; Schulte, K.; et al. A tunable scaffold of microtubular graphite for 3D cell growth.
ACS Appl. Mater. Interfaces 2016, 8, 14980–14985. [CrossRef] [PubMed]
153. Shimizu, K.; Ito, A.; Yoshida, T.; Yamada, Y.; Ueda, M.; Honda, H. Bone tissue engineering with human
mesenchymal stem cell sheets constructed using magnetite nanoparticles and magnetic force. J. Biomed.
Mater. Res. B 2007, 82, 471–480. [CrossRef] [PubMed]
154. Dykman, L.; Khlebtsov, N. Gold nanoparticles in biomedical applications: Recent advances and perspectives.
Chem. Soc. Rev. 2012, 41, 2256–2282. [CrossRef]
155. Boisselier, E.; Astruc, D. Gold nanoparticles in nanomedicine: Preparations, imaging, diagnostics, therapies
and toxicity. Chem. Soc. Rev. 2009, 38, 1759–1782. [CrossRef] [PubMed]
156. Ko, W.-K.; Heo, D.N.; Moon, H.-J.; Lee, S.J.; Bae, M.S.; Lee, J.B.; Sun, I.-C.; Jeon, H.B.; Park, H.K.; Kwon, I.K.
The effect of gold nanoparticle size on osteogenic differentiation of adipose-derived stem cells. J. Colloid
Interface Sci. 2015, 438, 68–76. [CrossRef] [PubMed]
157. Liu, D.; Zhang, J.; Yi, C.; Yang, M. The effects of gold nanoparticles on the proliferation, differentiation, and
mineralization function of MC3T3-E1 cells in vitro. Chin. Sci. Bull. 2010, 55, 1013–1019. [CrossRef]
158. Hasan, A.; Morshed, M.; Memic, A.; Hassan, S.; Webster, T.J.; Marei, H.E.-S. Nanoparticles in tissue
engineering: Applications, challenges and prospects. Int. J. Nanomed. 2018, 13, 5637–5655. [CrossRef]
159. Suarasan, S.; Focsan, M.; Soritau, O.; Maniu, D.; Astilean, S. One-pot, green synthesis of gold nanoparticles
by gelatin and investigation of their biological effects on Osteoblast cells. Colloids Surf. B 2015, 132, 122–131.
[CrossRef]
160. Jaconi, M. Nanomedicine: Gold nanowires to mend a heart. Nat. Nanotechnol. 2011, 6, 692–693. [CrossRef]
161. El Fray, M.; Boccaccini, A.R. Novel hybrid PET/DFA–TiO2 nanocomposites by in situ polycondensation.
Mater. Lett. 2005, 59, 2300–2304. [CrossRef]
162. Lim, D.; Lee, E.; Kim, H.; Park, S.; Baek, S.; Yoon, J. Multi stimuli-responsive hydrogel microfibers containing
magnetite nanoparticles prepared using microcapillary devices. Soft Matter 2015, 11, 1606–1613. [CrossRef]
[PubMed]
163. Rane, A.A.; Christman, K.L. Biomaterials for the treatment of myocardial infarction: A 5-year update. J. Am.
Coll. Cardiol. 2011, 58, 2615–2629. [CrossRef]
164. Shi, W.; Zhang, Z.-J.; Yuan, Y.; Xing, E.-M.; Qin, Y.; Peng, Z.-J.; Zhang, Z.-P.; Yang, K.-Y. Optimization
of parameters for preparation of docetaxel-loaded PLGA nanoparticles by nanoprecipitation method.
J. Huazhong Univ. Sci. Med. 2013, 33, 754–758. [CrossRef]
165. Shin, S.R.; Shin, C.; Memic, A.; Shadmehr, S.; Miscuglio, M.; Jung, H.Y.; Jung, S.M.; Bae, H.;
Khademhosseini, A.; Tang, X.S.; et al. Aligned carbon nanotube-based flexible gel substrates for engineering
bio-hybrid tissue actuators. Adv. Funct. Mater. 2015, 25, 4486–4495. [CrossRef]
Int. J. Mol. Sci. 2020, 21, 2521 28 of 29

166. Bei, H.P.; Yang, Y.; Zhang, Q.; Tian, Y.; Luo, X.; Yang, M.; Zhao, X. Graphene-based nanocomposites for
neural tissue engineering. Molecules 2019, 24, 658. [CrossRef]
167. Galiano, K.; Pleifer, C.; Engelhardt, K.; Brössner, G.; Lackner, P.; Huck, C.; Lass-Flörl, C.; Obwegeser, A.
Silver segregation and bacterial growth of intraventricular catheters impregnated with silver nanoparticles
in cerebrospinal fluid drainages. Neurol. Res. 2008, 30, 285–287. [CrossRef]
168. Bindhu, M.R.; Umadevi, M. Antibacterial activities of green synthesized gold nanoparticles. Mater. Lett.
2014, 120, 122–125. [CrossRef]
169. Tiwari, M.; Jain, P.; Chandrashekhar Hariharapura, R.; Narayanan, K.; Bhat, K.U.; Udupa, N.; Rao, J.V.
Biosynthesis of copper nanoparticles using copper-resistant Bacillus cereus, a soil isolate. Process Biochem.
2016, 51, 1348–1356. [CrossRef]
170. Nangmenyi, G.; Economy, J. Nanometallic particles for oligodynamic microbial disinfection. In Nanotechnology
Applications for Clean Water; Elsevier: Amsterdam, The Netherlands, 2009; pp. 3–15.
171. Prasher, P.; Singh, M.; Mudila, H. Oligodynamic effect of silver nanoparticles: A review. BioNanoScience 2018,
8, 951–962. [CrossRef]
172. Li, X.; Wang, L.; Fan, Y.; Feng, Q.; Cui, F.-Z. Biocompatibility and toxicity of nanoparticles and nanotubes.
J. Nanomater. 2012, 2012, 548389. [CrossRef]
173. Wang, L.; Hu, C.; Shao, L. The antimicrobial activity of nanoparticles: Present situation and prospects for the
future. Int. J. Nanomed. 2017, 12, 1227–1249. [CrossRef]
174. Kolarova, K.; Samec, D.; Kvitek, O.; Reznickova, A.; Rimpelova, S.; Svorcik, V. Preparation and characterization
of silver nanoparticles in methyl cellulose matrix and their antibacterial activity. JPN J. Appl. Phys. 2017, 56,
06GG09. [CrossRef]
175. Jones, R.S.; Draheim, R.R.; Roldo, M. Silver nanowires: Synthesis, antibacterial activity and biomedical
applications. Appl. Sci.-Basel 2018, 8. [CrossRef]
176. Polivkova, M.; Valova, M.; Siegel, J.; Rimpelova, S.; Hubacek, T.; Lyutakov, O.; Svorcik, V. Antibacterial
properties of palladium nanostructures sputtered on polyethylene naphthalate. RSC Adv. 2015, 5, 73767–73774.
[CrossRef]
177. Rezaei-Zarchi, S.; Imani, S.; mohammad Zand, A.; Saadati, M.; Zaghari, Z. Study of bactericidal properties of
carbohydrate-stabilized platinum oxide nanoparticles. Int. Nano Lett. 2012, 2, 21. [CrossRef]
178. Galarraga-Vinueza, M.E.; Passoni, B.; Benfatti, C.A.M.; Mesquita-Guimarães, J.; Henriques, B.; Magini, R.S.;
Fredel, M.C.; Meerbeek, B.V.; Teughels, W.; Souza, J.C.M. Inhibition of multi-species oral biofilm by bromide
doped bioactive glass. J. Biomed. Mater. Res. A 2017, 105, 1994–2003. [CrossRef]
179. Vasita, R.; Katti, D. Nanofiber and their application in tissue engineering. Int. J. Nanomed. 2006, 1, 15.
[CrossRef]
180. Liu, X.; Li, X.; Fan, Y.; Zhang, G.; Li, D.; Dong, W.; Sha, Z.; Yu, X.; Feng, Q.; Cui, F.; et al. Repairing goat tibia
segmental bone defect using scaffold cultured with mesenchymal stem cells. J. Biomed. Mater. Res. B 2010,
94, 44–52. [CrossRef]
181. Moore, W.R.; Graves, S.E.; Bain, G.I. Synthetic bone graft substitutes. ANZ J. Surg. 2001, 71, 354–361.
[CrossRef]
182. Slepicka, P.; Siegel, J.; Lyutakov, O.; Kasalkova, N.S.; Kolska, Z.; Bacakova, L.; Svorcik, V. Polymer
nanostructures for bioapplications induced by laser treatment. Biotechnol. Adv. 2018, 36, 839–855. [CrossRef]
183. Peterbauer, T.; Yakunin, S.; Siegel, J.; Hering, S.; Fahrner, M.; Romanin, C.; Heitz, J. Dynamics of spreading
and alignment of cells cultured in vitro on a grooved polymer surface. J. Nanomater. 2011, 2011, 413079.
[CrossRef]
184. Diez-Escudero, A.; Espanol, M.; Ginebra, M.P. Synthetic bone graft substitutes: Calcium-based biomaterials.
In Dental Implants and Bone Grafts: Materials and Biological Issues; Alghamdi, H., Jansen, J., Eds.; Elsevier:
Amsterdam, The Netherlands, 2019; pp. 125–157. [CrossRef]
185. Ribas, R.G.; Schatkoski, V.M.; Montanheiro, T.L.D.; de Menezes, B.R.C.; Stegemann, C.; Leite, D.M.G.;
Thim, G.P. Current advances in bone tissue engineering concerning ceramic and bioglass scaffolds: A review.
Ceram. Int. 2019, 45, 21051–21061. [CrossRef]
186. Zhang, J.; Zhou, H.; Yang, K.; Yuan, Y.; Liu, C. RhBMP-2-loaded calcium silicate/calcium phosphate cement
scaffold with hierarchically porous structure for enhanced bone tissue regeneration. Biomaterials 2013, 34,
9381–9392. [CrossRef]
Int. J. Mol. Sci. 2020, 21, 2521 29 of 29

187. Li, X.; van Blitterswijk, C.A.; Feng, Q.; Cui, F.; Watari, F. The effect of calcium phosphate microstructure on
bone-related cells in vitro. Biomaterials 2008, 29, 3306–3316. [CrossRef]
188. Xiao, J.; Wan, Y.Z.; Yang, Z.W.; Huang, Y.; Zhu, Y.; Yao, F.L.; Luo, H.L. Simvastatin-loaded nanotubular
mesoporous bioactive glass scaffolds for bone tissue engineering. Microporous Mesoporous Mater. 2019, 288,
109570. [CrossRef]
189. Zhou, P.H.; Guan, J.J.; Xu, P.P.; Zhao, J.W.; Zhang, C.C.; Zhang, B.; Mao, Y.J.; Cui, W.G. Cell therapeutic
strategies for spinal cord injury. Adv. Wound Care 2019, 8, 585–605. [CrossRef]
190. Kam, N.W.S.; Jan, E.; Kotov, N.A. Electrical stimulation of neural stem cells mediated by humanized carbon
nanotube composite made with extracellular matrix protein. Nano Lett. 2009, 9, 273–278. [CrossRef]
191. Yang, F.; Murugan, R.; Ramakrishna, S.; Wang, X.; Ma, Y.X.; Wang, S. Fabrication of nano-structured porous
PLLA scaffold intended for nerve tissue engineering. Biomaterials 2004, 25, 1891–1900. [CrossRef]
192. Yang, F.; Murugan, R.; Wang, S.; Ramakrishna, S. Electrospinning of nano/micro scale poly(l-lactic acid)
aligned fibers and their potential in neural tissue engineering. Biomaterials 2005, 26, 2603–2610. [CrossRef]
193. Wang, L.; Kisaalita, W.S. Characterization of micropatterned nanofibrous scaffolds for neural network activity
readout for high-throughput screening. J. Biomed. Mater. Res. B 2010, 94, 238–249. [CrossRef]
194. Li, W.; Guo, Y.; Wang, H.; Shi, D.; Liang, C.; Ye, Z.; Qing, F.; Gong, J. Electrospun nanofibers immobilized
with collagen for neural stem cells culture. J. Mater. Sci. Mater. Med. 2008, 19, 847–854. [CrossRef]
195. Mozaffarian, D.; Benjamin, E.J.; Go, A.S.; Arnett, D.K.; Blaha, M.J.; Cushman, M.; de Ferranti, S.; Despres, J.P.;
Fullerton, H.J.; Howard, V.J.; et al. Heart disease and stroke statistics-2015 update A report from the american
heart association. Circulation 2015, 131, 29–322.
196. Nagaya, N.; Kangawa, K.; Itoh, T.; Iwase, T.; Murakami, S.; Miyahara, Y.; Fujii, T.; Uematsu, M.; Ohgushi, H.;
Yamagishi, M.; et al. Transplantation of mesenchymal stem cells improves cardiac function in a rat model of
dilated cardiomyopathy. Circulation 2005, 112, 1128–1135. [CrossRef]
197. Han, J.; Park, J.; Kim, B.-S. Integration of mesenchymal stem cells with nanobiomaterials for the repair of
myocardial infarction. Adv. Drug Deliv. Rev. 2015, 95, 15–28. [CrossRef]
198. Wickham, A.M.; Islam, M.M.; Mondal, D.; Phopase, J.; Sadhu, V.; Tamás, É.; Polisetti, N.; Richter-Dahlfors, A.;
Liedberg, B.; Griffith, M. Polycaprolactone–thiophene-conjugated carbon nanotube meshes as scaffolds for
cardiac progenitor cells. J. Biomed. Mater. Res. B 2014, 102, 1553–1561. [CrossRef]
199. Martins, A.M.; Eng, G.; Caridade, S.G.; Mano, J.F.; Reis, R.L.; Vunjak-Novakovic, G. Electrically conductive
chitosan/carbon scaffolds for cardiac tissue engineering. Biomacromolecules 2014, 15, 635–643. [CrossRef]
200. Kharaziha, M.; Shin, S.R.; Nikkhah, M.; Topkaya, S.N.; Masoumi, N.; Annabi, N.; Dokmeci, M.R.;
Khademhosseini, A. Tough and flexible CNT–polymeric hybrid scaffolds for engineering cardiac constructs.
Biomaterials 2014, 35, 7346–7354. [CrossRef]
201. Singh, A.; AS, A.; Gade, W.; Vats, T.; Lenardi, C.; Milani, P. Nanomaterials: New generation therapeutics in
wound healing and tissue repair. Curr. Nanosci. 2010, 6, 577–586. [CrossRef]
202. Muthuvignesh, V.; Jaganathan, S.; Manikandan, A. Nanomaterials as a game changer in the management
and treatment of diabetic foot ulcers. RSC Adv. 2016, 6, 114859–114878.
203. Mohamed, A.; Xing, M.M. Nanomaterials and nanotechnology for skin tissue engineering. Int. J. Burns Trauma
2012, 2, 29–41.

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).

SAL-Laser Guided Rocket FZ275 LGR (Thales) 02-2021 (1) - 1
No ratings yet
SAL-Laser Guided Rocket FZ275 LGR (Thales) 02-2021 (1) - 1
2 pages
Tezpur University - (TEZU), Napaam
No ratings yet
Tezpur University - (TEZU), Napaam
18 pages
Nanomaterials in Tissue Engineering Fabrication and Applications Entire Volume Download
100% (13)
Nanomaterials in Tissue Engineering Fabrication and Applications Entire Volume Download
16 pages
Biomaterials Notes by Nimisha Chennakadan
100% (1)
Biomaterials Notes by Nimisha Chennakadan
14 pages
Technical Considerations For TBM Tunneling For Mining Projects
No ratings yet
Technical Considerations For TBM Tunneling For Mining Projects
8 pages
Nanofibrous Substrates For Bone Tissue Biomimetic Hydroxyapatite-Containing Composite
No ratings yet
Nanofibrous Substrates For Bone Tissue Biomimetic Hydroxyapatite-Containing Composite
18 pages
Sunrise Systems: Presentation Pipenet Software
No ratings yet
Sunrise Systems: Presentation Pipenet Software
35 pages
4estimation and Hypothesis Testing (DB) (Compatibility Mode)
No ratings yet
4estimation and Hypothesis Testing (DB) (Compatibility Mode)
170 pages
WB35 All
No ratings yet
WB35 All
58 pages
Can Nanotechnology Help To Repair The Body
No ratings yet
Can Nanotechnology Help To Repair The Body
27 pages
Presented BY:-Pratik Gupta (Eee 5 Sem)
No ratings yet
Presented BY:-Pratik Gupta (Eee 5 Sem)
21 pages
The Jeans Redesign: Guidelines
No ratings yet
The Jeans Redesign: Guidelines
18 pages
Applications of Nanotechnology in Tissue Engineering
No ratings yet
Applications of Nanotechnology in Tissue Engineering
22 pages
Feng 2021
No ratings yet
Feng 2021
52 pages
Textile Based Tissue Engineering Scaffolds
No ratings yet
Textile Based Tissue Engineering Scaffolds
33 pages
Allied School Zakariya Campus Multan: Geography of The Muslim World
No ratings yet
Allied School Zakariya Campus Multan: Geography of The Muslim World
3 pages
Tissueengineering
No ratings yet
Tissueengineering
23 pages
Nanofibers and Their Applications in Tissue Engineering: Rajesh Vasita Dhirendra S Katti
No ratings yet
Nanofibers and Their Applications in Tissue Engineering: Rajesh Vasita Dhirendra S Katti
16 pages
Nanostructured Materials For
No ratings yet
Nanostructured Materials For
8 pages
2023 - Fiber Review With Smitha Rao PDF
No ratings yet
2023 - Fiber Review With Smitha Rao PDF
41 pages
NIH Public Access: Author Manuscript
No ratings yet
NIH Public Access: Author Manuscript
31 pages
Radiologi
No ratings yet
Radiologi
13 pages
Mandeep Final Thesis
No ratings yet
Mandeep Final Thesis
68 pages
Metal Nanoparticles Advanced and Promising Technology in Diabetic Wound Therapy
No ratings yet
Metal Nanoparticles Advanced and Promising Technology in Diabetic Wound Therapy
29 pages
NIH Public Access: Author Manuscript
No ratings yet
NIH Public Access: Author Manuscript
17 pages
Various Manufacturing
No ratings yet
Various Manufacturing
16 pages
Biomimetic Materials For Tissue Engineering
No ratings yet
Biomimetic Materials For Tissue Engineering
12 pages
What IS Diabetes?
No ratings yet
What IS Diabetes?
25 pages
Tian 2016
No ratings yet
Tian 2016
12 pages
Application of Synthetic Polymers in Bone and Tissue Engineering
No ratings yet
Application of Synthetic Polymers in Bone and Tissue Engineering
59 pages
Antimicrobial Nano-Agents The Copper Age
No ratings yet
Antimicrobial Nano-Agents The Copper Age
22 pages
Brendon M. Baker Et Al - Fabrication and Modeling of Dynamic Multipolymer Nanofibrous Scaffolds
No ratings yet
Brendon M. Baker Et Al - Fabrication and Modeling of Dynamic Multipolymer Nanofibrous Scaffolds
10 pages
Fabrizio Gelain - Novel Opportunities and Challenges Offered by Nanobiomaterials in Tissue Engineering
No ratings yet
Fabrizio Gelain - Novel Opportunities and Challenges Offered by Nanobiomaterials in Tissue Engineering
10 pages
Tesi_Dottorato_Celesti
No ratings yet
Tesi_Dottorato_Celesti
200 pages
Yi 2018
No ratings yet
Yi 2018
15 pages
Copper Nanoparticles Synthesis and Antimicrobial Applications
No ratings yet
Copper Nanoparticles Synthesis and Antimicrobial Applications
18 pages
Review Article: Chitosan and Its Potential Use As A Scaffold For Tissue Engineering in Regenerative Medicine
No ratings yet
Review Article: Chitosan and Its Potential Use As A Scaffold For Tissue Engineering in Regenerative Medicine
16 pages
Functional Regeneration of Tendons Using Scaffolds With Physical Anisotropy Engineered Via Microarchitectural Manipulation
No ratings yet
Functional Regeneration of Tendons Using Scaffolds With Physical Anisotropy Engineered Via Microarchitectural Manipulation
12 pages
Tissue Engineering: Properties of Ideal /scaffolds Characteristics
No ratings yet
Tissue Engineering: Properties of Ideal /scaffolds Characteristics
4 pages
Antimicrobial Activity of Metals - Mechanisms, Molecular Targets and Applications
No ratings yet
Antimicrobial Activity of Metals - Mechanisms, Molecular Targets and Applications
14 pages
Biomaterials For Cellular Scaffolding
No ratings yet
Biomaterials For Cellular Scaffolding
57 pages
Review in Electrospinning 2
No ratings yet
Review in Electrospinning 2
25 pages
1 s2.0 S0939641121000369 Main
No ratings yet
1 s2.0 S0939641121000369 Main
14 pages
A Research Work On: Chitosan Film Containing Human Hair Derived Keratin For Biomedical Applications
No ratings yet
A Research Work On: Chitosan Film Containing Human Hair Derived Keratin For Biomedical Applications
12 pages
1 s2.0 S1385894723053470 Main
No ratings yet
1 s2.0 S1385894723053470 Main
24 pages
Antibacterial and Biocompatible Titanium-Copper Oxide Coating May Be A Potential Strategy To Reduce Periprosthetic Infection An in Vitro Study
No ratings yet
Antibacterial and Biocompatible Titanium-Copper Oxide Coating May Be A Potential Strategy To Reduce Periprosthetic Infection An in Vitro Study
11 pages
Termpaper 214bm1381 4thsem
No ratings yet
Termpaper 214bm1381 4thsem
5 pages
LogisticPolicy Punjab 19may2023
No ratings yet
LogisticPolicy Punjab 19may2023
54 pages
Synthetic Biopolymer Nanocomposites For Tissue
No ratings yet
Synthetic Biopolymer Nanocomposites For Tissue
55 pages
Copper Nanoparticles Have Negligible Direct Antibacterial Impact
No ratings yet
Copper Nanoparticles Have Negligible Direct Antibacterial Impact
8 pages
Homework 2
No ratings yet
Homework 2
2 pages
IWGIA Book The Indigenous World 2024 ENG
No ratings yet
IWGIA Book The Indigenous World 2024 ENG
688 pages
IJN 2006 1 (1) Vasita
No ratings yet
IJN 2006 1 (1) Vasita
16 pages
Solution Blow Spinning of Highly Deacetylated Chitosan Nanofiber Scaffolds
No ratings yet
Solution Blow Spinning of Highly Deacetylated Chitosan Nanofiber Scaffolds
11 pages
Biomaterials For Tissue Engineering and Regenerative Medicine
No ratings yet
Biomaterials For Tissue Engineering and Regenerative Medicine
21 pages
CEGSI - Company Profile - 2023 - Ver6.0
No ratings yet
CEGSI - Company Profile - 2023 - Ver6.0
47 pages
Journal of Drug Delivery Science and Technology 2023
No ratings yet
Journal of Drug Delivery Science and Technology 2023
13 pages
2023-Madappura...Madduri-Sf hydrogels for drug delivery
No ratings yet
2023-Madappura...Madduri-Sf hydrogels for drug delivery
19 pages
2022-Guangfei Li and Shan Sun-Silk in tissue engineering
No ratings yet
2022-Guangfei Li and Shan Sun-Silk in tissue engineering
24 pages
thoracic-range-of-movement-exercises-985-v1
No ratings yet
thoracic-range-of-movement-exercises-985-v1
7 pages
Application of Nanomaterials in tissue engineering
No ratings yet
Application of Nanomaterials in tissue engineering
18 pages
Structural Design, Fabrication and Evaluation of Resorbable Fiber-Based Tissue Engineering Scaffolds
No ratings yet
Structural Design, Fabrication and Evaluation of Resorbable Fiber-Based Tissue Engineering Scaffolds
30 pages
Incorporation of Inorganic Bioceramics Into Electrospun Scaffolds For Tissue Engineering Applications - A Review - ScienceDirect
No ratings yet
Incorporation of Inorganic Bioceramics Into Electrospun Scaffolds For Tissue Engineering Applications - A Review - ScienceDirect
7 pages
polymers-14-01508-v2
No ratings yet
polymers-14-01508-v2
38 pages
Functional Scaffolding
No ratings yet
Functional Scaffolding
11 pages
IntroductiontoNano Biomaterials
No ratings yet
IntroductiontoNano Biomaterials
13 pages
10 1089@bioe 2020 0021
No ratings yet
10 1089@bioe 2020 0021
30 pages
Study Material Unit 3 Scaffold
No ratings yet
Study Material Unit 3 Scaffold
4 pages
Daniekingsley 2013
No ratings yet
Daniekingsley 2013
5 pages
Market Insight - District Cooling Market in GCC
100% (1)
Market Insight - District Cooling Market in GCC
8 pages
Polymers: A Comparative Review of Natural and Synthetic Biopolymer Composite Scaffolds
No ratings yet
Polymers: A Comparative Review of Natural and Synthetic Biopolymer Composite Scaffolds
51 pages
Selavip_Formulario_Postulacion_en-_2025
No ratings yet
Selavip_Formulario_Postulacion_en-_2025
14 pages
New Orthopaedic Biomaterial
No ratings yet
New Orthopaedic Biomaterial
2 pages
Soil Properties and Their Correlations - 2016 - Carter - Appendix A Soil Classification Systems
No ratings yet
Soil Properties and Their Correlations - 2016 - Carter - Appendix A Soil Classification Systems
14 pages
High Heat Primer: Technical Data ATO-56
No ratings yet
High Heat Primer: Technical Data ATO-56
2 pages
TiO2 paper (4)
No ratings yet
TiO2 paper (4)
5 pages
Hydranautics SWC5-LD (PW)
No ratings yet
Hydranautics SWC5-LD (PW)
1 page
Warrior 8 Software FOM
No ratings yet
Warrior 8 Software FOM
624 pages
s10856-024-06777-z
No ratings yet
s10856-024-06777-z
18 pages
Effect of Iron Doped Hydroxyapatite Nanoparticles on t 2019 Journal of Mater
No ratings yet
Effect of Iron Doped Hydroxyapatite Nanoparticles on t 2019 Journal of Mater
9 pages
Nanomaterials in Tissue Engineering Fabrication and Applications Digital PDF Download
No ratings yet
Nanomaterials in Tissue Engineering Fabrication and Applications Digital PDF Download
14 pages
Local Law 48
No ratings yet
Local Law 48
5 pages
Journal Orthopaedic Research - 2006 - Christenson - Nanobiomaterial Applications in Orthopedics
No ratings yet
Journal Orthopaedic Research - 2006 - Christenson - Nanobiomaterial Applications in Orthopedics
12 pages
Module 7 Switching System and Automatic Recloser
No ratings yet
Module 7 Switching System and Automatic Recloser
36 pages
TiO2 Paper
No ratings yet
TiO2 Paper
2 pages
TiO2 paper (1)
No ratings yet
TiO2 paper (1)
4 pages
Dump Trucck Hire Charge
No ratings yet
Dump Trucck Hire Charge
1 page
Module 3 MAS
No ratings yet
Module 3 MAS
30 pages
SEM IV ANNOTATIONS
No ratings yet
SEM IV ANNOTATIONS
3 pages
Psychology 188 Chapter 3 Guide
No ratings yet
Psychology 188 Chapter 3 Guide
6 pages
A_Review_of_Nanofiber_Current_Progress_in_Applicat
No ratings yet
A_Review_of_Nanofiber_Current_Progress_in_Applicat
10 pages
gegp101
No ratings yet
gegp101
23 pages
Control Pitch, Roll and Yaw Axis of Aircraft
No ratings yet
Control Pitch, Roll and Yaw Axis of Aircraft
49 pages
Heterogeneity in Composite Materials
From Everand
Heterogeneity in Composite Materials
Pasquale De Marco
No ratings yet
Green Tio2 as Nanocarriers for Targeting Cervical Cancer Cell Lines
From Everand
Green Tio2 as Nanocarriers for Targeting Cervical Cancer Cell Lines
Mythreyi M
No ratings yet
Nanocomposite Hydrogels: Advances in Drug Delivery and Tissue Engineering Applications
From Everand
Nanocomposite Hydrogels: Advances in Drug Delivery and Tissue Engineering Applications
Fouad Sabry
No ratings yet

Nanostructured Materials For Artificial Tissue Replacements

Uploaded by

Nanostructured Materials For Artificial Tissue Replacements

Uploaded by

International Journal of

Keywords: nanomaterials; tissue engineering; biologic properties; mechanical properties; antibacterial

Int. J. Mol. Sci. 2020, 21, 2521; doi:10.3390/ijms21072521 www.mdpi.com/journal/ijms

• Porosity and pore size,

Site of Application Cell Culture Polymeric Scaffold

Int. J. Mol. Sci. 2019, 20, x FOR PEER REVIEW 8 of 29

Nanostructure type Advantage RegeneratedTissue

Metal nanoparticles represent dynamically developing group of nanomaterials which excel in

4. Opportunities of Properties Enhancement

4.1. Biologic Properties

4.4. Antibacterial Properties

Int. J. Mol. Sci. 2019, 20, x FOR PEER REVIEW 13 of 29

5. Composite Organic/Inorganic Nanomaterials

5.1. Cartilage Tissue Engineering

5.2. Bone Tissue Engineering

Int. J. Mol. Sci.

5.5. Skin Tissue Engineering

You might also like