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 Chapter 16

Biomaterials and Stem Cells: Promising Tools in Tissue

Engineering and Biomedical Applications
Małgorzata Sekuła and Ewa K. Zuba-Surma
Małgorzata Sekuła and Ewa K. Zuba‐Surma
Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.70122

Abstract
Biomaterial sciences and tissue engineering approaches are currently fundamental strat‐
egies for the development of regenerative medicine. Stem cells (SCs) are a unique cell
type capable of self‐renewal and reconstructing damaged tissues. At the present time,
adult SCs isolated from postnatal tissues are widely used in clinical applications. Their
characteristics such as a multipotent differentiation capacity and immunomodulatory
activity make them a promising tool to use in patients. Modern material technologies
allow for the development of innovative biomaterials that closely correspond to require‐
ments of the current biomedical application. Biomaterials, such as ceramics and metals,
are already used as implants to replace or improve the functionality of the damaged
tissue or organ. However, the continuous development of modern technology opens
new insights of polymeric and smart material applications. Moreover, biomaterials may
enhance the SCs biological activity and their implementation by establishing a specific
microenvironment mimicking natural cell niche. Thus, the synergistic advancement in
the fields of biomaterial and medical sciences constitutes a challenge for the development
of effective therapies in humans including combined applications of novel biomaterials
and SCs populations.

Keywords: adult stem cells, biomaterials, regenerative medicine, tissue engineering

1. Introduction

Regenerative medicine represents a new interdisciplinary field of clinical science focused on

the development and implementation of novel strategies to enhance the process of regenera‐
tion of impaired cells, tissues and organs as well as replacing damaged cells with new, fully
functional cells of the required phenotype [1, 2].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons
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362 Biomaterials in Regenerative Medicine

To improve the effectiveness of such regeneration processes, one of the potential approaches
is application of stem cell (SC)‐based therapy. In addition, the combination of stem cells
with biocompatible materials that may constitute a scaffold for the seeded cells may lead to
enforcement of biological activity of stem cells and as such accelerate the process of regenera‐
tion or restoration of impaired tissue [3, 4].

2. Therapeutic applications of stem cells

2.1. Classification and characteristics of stem cells (SCs)

Stem cells (SCs) are a unique type of cells characterized by the ability to (i) self‐renewal
through unlimited cell divisions and (ii) differentiate into other types of specialized cells,
including epithelial, muscle, neuronal cells and others [5, 6].
Based on the origin and source of isolation, SCs may be included in two main groups: (i)
embryonic SCs (ESCs)—derived from embryos at different stages of development and (ii)
adult SCs (ASCs)—isolated from several postnatal and adult tissue sources, including the
umbilical cord, cord blood, bone marrow, adipose tissue, central nervous system, retina, skel‐
etal muscle and other mature tissues [7, 8]. The differentiation capacity of embryonic SCs
allows them to form any individual organs and fully differentiated cells of the whole body,
which corresponds to pluripotency of these SCs. In opposite, most of adult SCs are multi‐
potent and lineage‐restricted (monopotent) and generally give rise to certain cell types of
one germ layer or cell lineage. They residue in several niches, including bone marrow, liver,
muscle, brain and others, where they may be activate towards tissue‐ or organ‐specific cells
under certain physiologic or experimental conditions. Moreover, it has been shown that adult
SCs may provide efficient regeneration of impaired organs in both preclinical and clinical
conditions [7].

Based on the differentiation capacity, SCs populations belong to the following types [5, 9–11]:
• Totipotent SCs (TSCs)—The most developmentally primitive and potent SCs are capable
to differentiate into any cell type from three germ layers (mesoderm, ectoderm and endo‐
derm) forming whole organism as well as into extra‐embryonic tissues such as placenta;
the best examples of TSCs are zygote and first blastomeres [10–13].
• Pluripotent SCs (PSCs)—The cells sustaining the capacity to differentiate into all cell types
from three germ layers, but they are not able to give rise to placenta; PSCs are naturally
present in developing embryo in stage of morula, in inner cell mass (ICM) of developing
blastocyst and in the epiblast of gastrula and in limited number may also be found in adult
tissues as remnants from embryonic development [9, 14]; PSCs may also be de novo created
via genetic reprogramming of somatic cells and are called ‘induced PSCs’ (iPS cells) [11, 15].

• Multipotent SCs—The SCs typically capable to give rise to all cell types within one germ
layer; the best described examples are mesenchymal SCs (MSCs) isolated from several
adult and postnatal tissues [10, 16–18];
 Biomaterials and Stem Cells: Promising Tools in Tissue Engineering and Biomedical Applications 363
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• Unipotent SCs (progenitors)—The cells capable to differentiate into one or two particular
types of specialized cell present in particular tissue type; this group includes several popu‐
lation of tissue‐committed progenitors such as endothelial progenitor cells, cardiac SCs,
satellite cells of skeletal muscles, neural progenitors and others [5, 9, 10].

2.2. Types of SCs with potential clinical application

Recently, more attention has been directed to potential utilization of SCs in clinical applica‐
tions in patients. Due to the legal and ethical restrictions, the employment of embryonic SCs,
which possess the largest spectrum of differentiation capacity, is controversial and prohib‐
ited in many countries. Moreover, SCs with pluripotent characteristics may lead to adverse
side effects following their injection including teratoma formation [19, 20]. Therefore, the
therapies employing adult SCs play a major role in human treatment as safe and effective
approaches. Transplantations of autologous SCs isolated from mobilized peripheral blood or
bone marrow are currently widely used in haematological patients with malignancies such
as leukaemia and lymphoma [21]. Moreover, haematopoietic stem cells (HSCs) residing pre‐
dominantly in adult bone marrow are widely used for bone marrow reconstitution in patients
suffering from several genetic and autoimmune diseases, blood cancers and haematopoietic
defects [5, 7].
Current growing expectations for further advancements in regenerative medicine are highly
focused on mesenchymal stem/stromal cells (MSCs) belonging to adult SCs isolated from sev‐
eral tissue types [16, 18, 22, 23]. MSCs are multipotent, non‐haematopoietic cells, which can be
isolated from various sources including bone marrow, adipose tissue, cord blood, umbilical
cord, Wharton’s jelly and other tissues of the adult organism [22, 24]. Isolation of this type of
cells does not raise any ethical concerns and is a relatively easy procedure. Moreover, MSCs
are characterized by low immunogenicity with simultaneous immunomodulatory effect, and
after transplantation, teratoma formation does not occur in the recipient organism [16, 18, 22,
23, 25]. Furthermore, potential regenerative applicability of MSCs is also enhanced by their
paracrine activity related to several molecules released to their environment that may impact
on other neighbouring cells affecting their functions [22, 25]. MSCs produce and release bioac‐
tive molecules, including multitude growth factors (e.g. TGF‐β1, bFGF, BMP‐4), anti‐inflam‐
matory factors (e.g. IL‐10, PGE2, HGF) and cytoprotective agents (e.g. IL‐6, MCP‐1, IGF‐1),
which promote resident cells to divide and remodel the damaged tissue [26]. All these listed
features make MSCs as promising tool for biomedical research.
MSCs possess a robust proliferation capacity as well as a potential to differentiate into several
lineages of mesodermal origin, including bone, cartilage and adipose tissue [23]. Moreover,
they have been also shown to give rise to other cell types, such as endothelial, cardiac or liver
cells, which may also be utilized in tissue regeneration [16, 27]. These unique biological values
may be utilized for the development of personalized treatment strategy for several diseases
and provide the progress in establishing modern cell‐based therapy. Cell‐based therapy rep‐
resents a promising perspective of treatment directed at the regeneration of damaged tissues
or organs using stem cells or progenitor cells both in the autologous and allogeneic system
[16, 28–30].
364 Biomaterials in Regenerative Medicine

According to the current U.S. National Institutes of Health database including clinical trials
conducted worldwide, there are currently more than 240 clinical trials being conducted in the
world employing MSCs in patients [31]. Examples of the application of MSCs isolated from
different sources in the treatment of selected diseases are shown in Table 1.

One of the great new opportunities in medical science is the possibility of obtaining the
induced pluripotent SCs (iPS cells) by genetic reprogramming of mature cells into the stage of
pluripotency [15]. Due to the discovery of this phenomenon, professor Shinya Yamanaka was
honoured with the Nobel Prize in medicine and physiology in 2012. Since then, iPS cells consti‐
tute an excellent model for in vitro studies of molecular mechanisms associated with the devel‐
opment and progression of several diseases, including Parkinson’s disease [32], Huntington
disease [33], Down syndrome [34] and others. Moreover, dozens of laboratories are questing
for optimal utilization of these cells in tissue regeneration. However, due to the possibility of
teratoma formation after iPS transplantation, their applications in medicine are still limited.

Thus, despite the fact that several new rising SCs types are being examined and optimized for
future applications, the most commonly applicable SCs in cell therapies of distinct human dis‐
eases are adult stem cells including predominantly MSCs derived from bone marrow, adipose
tissue and umbilical cord as well as HSCs harvested from bone marrow, mobilized peripheral
blood and cord blood [16, 18, 28–30].

Type of MSCs Condition ClinicalTrials.gov identifier

Umbilical cord‐derived MSCs Hepatic cirrhosis NCT02652351

Aplastic anaemia NCT03055078

Stroke NCT02580019

Pneumoconiosis NCT02668068

Rheumatoid arthritis NCT02643823

Sweat gland diseases NCT02304562

Bone marrow‐derived MSCs Acute myocardial infarction NCT01652209

Chronic myocardial ischaemia NCT02460770

Acute respiratory distress syndrome NCT02097641

Middle cerebral artery infarction NCT01461720

Prostate cancer NCT01983709

Stroke NCT02564328

Adipose‐derived MSCs Infantile spinal muscular atrophy NCT02855112

Multiple sclerosis NCT02326935

Hair restoration NCT02865421

Source: Ref. [31].

Table 1. The application of MSCs in selected clinical trials.

 Biomaterials and Stem Cells: Promising Tools in Tissue Engineering and Biomedical Applications 365
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2.3. Utilization of SC derivatives as a potential alternative to cell‐based therapy

Immunomodulatory properties of SCs are important features involved in tissue repair, which
are directly related to their paracrine activity. Despite the directly released molecules, mam‐
malian cells, including SCs, are able to produce extracellular vesicles (EVs) carrying bioac‐
tive factors, which may additionally be involved in the modulation of the repair process
of damaged tissues [35]. EVs represent heterogeneous population of small, circular struc‐
tures surrounded with the protein‐lipid membrane that are released by cells including SCs.
Importantly, the size and molecular composition of EVs are different and unique depending
on the cell type of origin and the mechanism of their biogenesis. Depending on the size of EVs,
they may be distinguished in apoptotic bodies (1–5 µm), microparticles (100 nm–1 µm) and
exosomes (30–100 nm) fractions [36, 37].

Several recent scientific reports indicate that EVs express surface markers characterizing the
cells from which they are released, along with EV‐specific antigens including tetraspanins
(CD9, CD63 and CD81), endosome or membrane‐binding proteins (TG101), signal transduc‐
tion or scaffolding proteins (syntenin) [36, 37]. Importantly, EVs may also include various
types of bioactive components (e.g. mRNA, miRNA and enzymes), as well as receptors, adhe‐
sion or signalling proteins [38, 39]. Importantly, the contents of EVs can be effectively trans‐
ferred to the target cells, change their function and impact in the regeneration of impaired
tissues. Moreover, the presence of protein‐lipid membrane on the surface of EVs can protect
their bioactive content from extracellular enzymes and therefore the cargo may be delivered
in a fully functional form into targeted cells [38, 40]. Thus, EVs are recognized as mediators
of intercellular communication and constitute an alternative or reinforcement of a standard
cell‐based therapy.

The biological relevance of EVs has been established in different experimental settings.
Depending on the origin and content of EVs, they may enhance immune system, endorse anti‐
tumour responses and thus may provide important tools for novel anti‐tumour therapies,
such as melanoma treatment [41]. EVs may also be utilized as drug delivery vehicles [42], in
regenerative medicine [43] and immune therapy [44]. Recently, our study also indicated that
SC‐derived EVs may be utilized as a novel tool for regenerative therapies of ischemic tissue
including in heart repair [38, 40].

However, further studies are required for comprehensive analysis of the mechanisms of EVs
action and potential clinical applications of these promising SC derivatives.

3. Medical application of selected natural and synthetic biomaterials

3.1. Material requirements for biomaterials

Biomaterial by definition is a ‘substance (other than a drug), synthetic or natural, that can be
used as a system or part of a system that treats, augments, or replaces any tissue, organ, or
function of the body’ [45]. Thus, according to the definition biomaterials are progressively
366 Biomaterials in Regenerative Medicine

used in tissue engineering. They may be utilized for the construction of implants to replace
lost or damaged organs or tissues and may also constitute a scaffold for enhanced stem cells
to reconstruct not fully functional tissue [45, 46].

Due to the wide range of potential applications of biomaterials in regenerative medicine, their
physical and chemical properties may be different [45, 47]. However, in order to use a bioma‐
terial in medical application, it should follow relevant requirements such as biocompatibility
and biofunctionality [45, 47]:

• Biocompatibility is the ability to integrate with the recipient’s cells in a safe manner and
without adverse side effects.

• Biofunctionality is the ability to perform a specific biological function, based on the rel‐
evant parameters of the physical and mechanical properties.

Other important properties of biomaterials, which are affecting the potential application in
medicine, include [45, 48, 49] the following:

• Biodegradation—Decomposition of the material in a natural way, when degradation prod‐

ucts remain in the human body but without adverse side effects.
• Bioresorbability—Decomposition of the material in a natural way at a certain period of
time after implantation. Non‐toxic‐degraded products are removed from the body via met‐
abolic pathways (hydrolytic or enzymatic degradation).
• Non‐toxicity—From the surface or porous of the material does not elute any toxic compo‐
nents, such as surfactants, stabilizers, catalysts, pigments and UV absorbents, which were
used during production and that are incompatible with living organisms.
• Mechanical properties—Biomaterial should possess particular mechanical properties con‐
sistent with the anatomical site into which it will be implanted.

3.2. Applications of biomaterials

Several biomaterials useful for distinct applications in medical sciences, including in tissue
repair and organ reconstruction, have already been developed over the last few decades [45,
47]. The biomaterial sciences are currently one of the highly advancing fields, which also
closely cooperate with biotechnological and medical studies. Recent advancement in regen‐
erative medicine strongly requires such strong support from biomaterial sciences, which may
provide novel solutions for tissue repair [4, 49].

Among the biomaterials recognized and developed for potential medical purposes, here are
multitude materials commonly present in natural sources or de novo designed and created for
such purposes.

3.2.1. Naturally derived biomaterials

Natural materials commonly present in nature such as agarose, collagen, alginate, chitosan,
hyaluronate or fibrin fully cooperate with living tissues of the recipient and possess low
 Biomaterials and Stem Cells: Promising Tools in Tissue Engineering and Biomedical Applications 367
http://dx.doi.org/10.5772/intechopen.70122

cytotoxicity [47, 48]. Moreover, they may exhibit specific protein‐binding sites that improve
integration with cells after transplantation [48]. Thus, they are considered predominantly
interesting for tissue engineering applications.
One of the most common natural biomaterials is collagen—an important component of con‐
nective tissue, including bones, tendons, ligaments and skin [46, 50]. Collagen is simply
absorbed into the body, is non‐toxic and exhibits a low immune response and as such is a
perfect biocompatible material with an adequate mechanical strength and flexibility for sev‐
eral applications. Moreover, collagen enhances cell adhesion to such surface, stimulates also
biological interactions between cells and facilitates restoration of the natural microenviron‐
ment of cell niche and thereby may support the reconstruction of several damaged tissues
[46, 48, 50].
Collagen may be employed for tissue engineering in the form of sponges, gels, hydrogels
and sheets. It may also be chemically crosslinked in order to enhance or alter the rate of
degradation of the fibres [51]. Currently, collagen preparations are used predominantly in
wound healing and cartilage regeneration. Injectable form of collagen is used for cosmetic
and aesthetic medicine as a tissue filler. In addition, collagen‐based membranes are used in
the periodontal treatment as a barrier preventing the migration of epithelial cells. It also forms
a favourable microenvironment for stem cells to facilitate reconstruction of the damaged area
[50, 51].

3.2.2. Synthetic biomaterials

Synthetic materials are considered as an alternative to natural materials. Due to their defined
chemical composition and the ability to control the mechanical and physical properties, they
are extensively used in therapeutic applications and basic biological studies [48, 52–55].
Due to distinct variants of polymerization reaction and formation of co‐polymers, multiple
synthetic polymers with wide range of physical and chemical properties may be achieved in
chemical laboratories. Moreover, novel technologies in the synthesis and formation of more
complex structures allow for the production of advanced composites [54]. Synthetic polymers,
such as poly(ethylene) (PE), polyurethanes (PUR), polylactides (PLA) and poly(glycolide)
(PGA), are widely employed as implants and components of medical devices [56]. Moreover,
polymers may constitute suitable scaffold for cell propagation and enhance their biological
activity, including neural stem cells, retinal progenitor cells or smooth muscle cells [55, 57, 58].
Thus, this group of biomaterials is currently in a special focus of scientists working on com‐
bined approaches using biocompatible scaffolds and stem cells for tissue repair [55, 57, 58].
Biodegradable polymers, including polyhydroxycarboxylic acids, such as PGA, PLA, poly(3‐
hydroxybutyrate), poly(4‐hydroxybutyrate) and poly(∈‐caprolactone) (PCL) are of wide
interest in the development of novel technologies [56]. One of their potential applications
is utilization in the treatment of cardiovascular diseases. Our recent studies have shown the
positive impact of both PCL and PLA scaffolds on proliferation, migration and proangiogenic
potential of mesenchymal SCs derived from umbilical cord tissue in vitro, suggesting the pos‐
sible applications of these materials in cardiovascular repair in vivo (unpublished data) [59].
368 Biomaterials in Regenerative Medicine

Synthetic polymers may also be used in biodegradable stents implanted after a heart attack
and greatly contribute to patient recovery [56]. Importantly, the material should have suitable
decomposition kinetics. Too long decomposition time (i.e. in the case of PLA or PGA) may
lead to late stent thrombosis or blockages [56, 60]. One of a possible solution of this problem is
to use rapidly biodegradable polymer stents coated with SCs to help rebuild damaged tissue
and additionally stimulate resident cells to grow.

Other types of common synthetic materials useful for biomedical applications are ceramics.
It has been well described that ceramic scaffolds, such as, for example, hydroxyapatite (HA)
and tri‐calcium phosphate (TCP), are characterized by biocompatibility, high mechanical
stiffness (Young’s modulus), very low elasticity and a hard brittle surface [49]. Due to their
chemical and structural similarity to the mineral phase of native bone, these materials may
enhance osteoblast proliferation and therefore they are widely utilized in bone regeneration
[61, 62]. Moreover, ceramics may be exploited in dental and orthopaedic procedures to fill
bone defects or as a bioactive coating material for implants to increase their integration after
transplantation [63, 64]. However, their clinical applications are still limited due to the dif‐
ficulties with the ability to change the shape of the material dedicated for transplantation and
controlling time of their degradation rate [49, 65].

Similarly, titanium (Ti)‐based metallic materials have been widely optimized for bone repair
due to their mechanical properties and resistance to corrosion following the transplantation
[66–68]. It has been shown that titanium scaffolds are effectively colonized by osteoblasts
responsible for bone formation and this process may be enhanced via additional modifica‐
tions of the scaffold surface by its roughening, coating with HA or graphene oxide (GO), as
well as its biofunctionalization with bioactive molecules such as heparin and bone morpho‐
genetic protein 2 (BMP‐2) [69–72].

Importantly, graphene in its different forms is currently being considered as a potential new
promising material for biomedical applications including tissue repair [73, 74]. This 2D carbon
biocompatible material exhibits great electrical, conductive and physical properties, which
make it interesting for potential applications for drug delivery and scaffold coating in regen‐
erative therapies [74, 75]. It has been shown that graphene may enhance osteogenic differenti‐
ation of SCs [72, 73]. Moreover, our recent data also suggest the beneficial impact of graphene
oxide (GO) on proliferative capacity, viability and differentiation potential of umbilical cord
tissue‐derived MSCs, which confirms the possibility of future graphene employment in tissue
repair [76].

3.2.3. Hydrogels

Hydrogels are frequently used biomaterials in the biomedical applications and represent sys‐
tems consisting of two or more compartments comprising a three‐dimensional (3D) network
of polymer chains and water that fills the spaces between the macromolecules [77, 78]. The
main characteristics of hydrogels include the biocompatibility and ability to swell in solution
until they reach a state of equilibrium. These allow them to be injected into the body in a
non‐invasive manner [77, 78].
 Biomaterials and Stem Cells: Promising Tools in Tissue Engineering and Biomedical Applications 369
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Hydrogels demonstrate transparency and bioadhesive properties and they are widely used
in the pharmaceutical and dermatological industries by local administration or filling the
defects caused by injury [77]. They may also be utilized as an injectable material for bone and
cartilage tissue engineering, which may be combined with appropriate cell injection [53, 78,
79]. It has been shown that in situ implementation of hydrogels promotes osteoblast differen‐
tiation [53, 79]. Therefore, injectable therapy constitutes a promising approach for non‐inva‐
sive technique of transplantation, where also cell‐based component may be added to enhance
tissue repair.

3.2.4. Smart materials

Smart materials represent a new generation of biomaterials, exceeding the functionality of the
currently widely used construction materials. Smart materials are characterized by the ability
to alter their physical characteristics in a controlled manner including changing the shape,
colour, stiffness or stickiness in response to several external stimuli, such as temperature,
hydrostatic pressure, electric and magnetic field or radiation [80]. These changes are related to
the revealing or eliciting the new functionality of the material and may be utilized in biomedi‐
cal applications. Through the common connection between the internal sensor, the activator
and a specific control mechanism, smart materials are able to respond to external stimuli.
Importantly, these mechanisms are also responsible for the return to the original state, when
a stimulant disappeared [80, 81].
Smart materials include several types such as listed below [52, 80, 82–84]:
• Colour changing materials—Materials that change colour in a reversible manner, depend‐
ing on electrical, optical or thermal changes. These types of materials are exploited, for
example, in optoelectronic components, lenses, lithium batteries, ferroelectric memory,
temperature sensors or as the indicators of battery consumption [80, 81].

• Light‐emitting materials—Materials emitting visible or invisible light, as a result of exter‐

nal stimuli such as short wavelength radiation (e.g. X‐rays, ultraviolet light), temperature
and electric voltage. They are utilized in electronics, filters for glasses, devices that detect
UV rays, in criminology and in geology to identify minerals and rocks. They may also be
exploited as a component of protective clothing, safety elements and warning materials
[80, 81].
• Shape memory materials—Metal alloys that change shape as a result of temperature increase
or decrease, respectively, to the set value. The reversibility of the process is to return to its
original shape by changing the temperature or under the influence of the applied motion (the
effect of pseudoelasticity). These materials are used in temperature sensors, electronics, robot‐
ics, telecommunications and production of medical devices (micro‐pump, surgical clamps,
orthodontic wire, long‐ and short‐term implants, suture tightening on a stiffen wound, ortho‐
paedic devices, bone nails, clamps, surgical instruments and others) [83, 84].

• Self‐assembling materials—Materials that exhibit the intrinsic ability to spontaneously

connect individual elements into an ordered 2D or 3D structure. In addition, they can also
370 Biomaterials in Regenerative Medicine

have the ability to bind metal atoms, ions, molecules or semiconductors. They are widely
used in biological research and nanotechnology, that is, in the tissue regeneration, as com‐
ponents for the storage of drugs, crystal engineering, as artificial proteins with pH‐sensitive
structure, as semi‐permeable membrane as well as for the production of electronic proces‐
sors and displays [52, 82].

• Self‐repairing materials—Structural damage of this type of material is automatically and

autonomously recovered by inducing a change in the shape or the self‐assembly of the mol‐
ecules. This process is not a method of complete repair of the impaired material; however,
it may be used in the military, automotive, aviation and electronics industries [52, 82].

4. Novel aspects of the application of stem cells and biomaterials in

tissue engineering and regenerative medicine

4.1. Biomaterials approaches for enhancement of SCs‐based therapy

Modern approaches in current regenerative medicine include developing biocompatible scaf‐

folds and combining them with living cell of selected type and bioactive molecules, in order
to enhance the regeneration process of damaged tissues and organs [47].

Growing evidence indicate different populations of stem cells as a promising tool that may
be utilized in tissue engineering and repair. Importantly, despite the regenerative prop‐
erties of SCs, the restoration processes in damaged tissue are long and may not often be
fully effective for functional recovery of damaged tissue. On the other hand, appropriate
stimulation of reparative capacity of SCs may be achieved by modulation of chemical and
physical properties of optimized biomaterials [47, 70, 77]. Therefore, simultaneous applica‐
tion of optimized and well‐combined SCs and biomaterials may open new perspectives for
the synergistic effective cooperation of both such components to improve the efficiency of
the regeneration process [77]. Biomaterials may enhance the biological activity of SCs by
establishing a specific niche related to their native microenvironment. This type of cell‐bio‐
material interactions leads to stimulation of cell adhesion, proliferation and directed differ‐
entiation of the cells implemented at the injured site [47, 70, 77]. Therefore, therapy based on
biomaterials and SCs opens new possibilities for the development of innovative medicine
[47, 77].
Currently, growing evidence is focused on encapsulation of native SCs prior to their trans‐
plantation [47, 85]. Cells encapsulation technique is based on the immobilization of cells in
a semi‐permeable membrane, which protects cells against mechanical damage and immune
system response. Notably, the construction of the microcapsules allows bidirectional diffu‐
sion of nutrients, oxygen and wastes and therefore provides appropriate conditions for cell
development [47, 85].
Encapsulated cells may be subjected to transplantation and directed differentiation. The
material used to construct the microcapsules should possess particular physical properties,
 Biomaterials and Stem Cells: Promising Tools in Tissue Engineering and Biomedical Applications 371
http://dx.doi.org/10.5772/intechopen.70122

such as biocompatibility, mechanical stability, permeability, appropriate size, strength and

durability [47]. One of the most common encapsulation materials is alginate. Due to the fact
that the procedure for cell encapsulation using alginate can be performed under physiologi‐
cal conditions (physiological temperature and pH) and using isotonic solutions, it is widely
distributed through clinical and industrial applications. Moreover, this natural biodegradable
polymer that mimics the extracellular matrix and promotes cell functions and metabolism has
been established in cartilage regenerative approaches [86, 87]. Microencapsulation technol‐
ogy represents a novel cell culture system that allows maintaining cell viability and differen‐
tiation of interested cell lines. It also may support the extracellular matrix production and cell
organization in reconstructed tissue [86].

5. Conclusions

Significant advancement of regenerative medicine, nanomedicine and biomaterials engi‐

neering offers extended possibilities to obtain novel, effective achievements, which may be
utilized in biomedical applications. The effect of interdisciplinary activity resulted in the
development of bioactive scaffolds that promote cell propagation and enhance their biologi‐
cal activity. However, some difficulties in biomaterial‐ and cell‐based therapy are still unclear
and need to be addressed for widespread investigations. Nevertheless, integrative research
in biomaterials and medicine fields is a challenge to develop effective therapies for cancer,
civilization diseases and provide further development of tissue engineering.

Acknowledgements

This work is supported by grants from the National Science Centre (NCN): SONATA BIS‐3
(UMO‐2013/10/E/NZ3/007500), SYMFONIA 3 (UMO‐2015/16/W/NZ4/00071) and the National
Centre for Research and Development (NCBR): STRATEGMED III (BioMiStem project; ID
303570) to EZS. The Faculty of Biochemistry, Biophysics and Biotechnology at the Jagiellonian
University, Krakow, Poland, is a partner of the Leading National Research Center (KNOW)
supported by the Ministry of Science and Higher Education.

Author details

Małgorzata Sekuła1 and Ewa K. Zuba‐Surma2*

*Address all correspondence to: ewa.zuba‐[email protected]

1 Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland

2 Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology,

Jagiellonian University, Krakow, Poland
372 Biomaterials in Regenerative Medicine

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