TON DUC THANG UNIVERSITY

Faculty of Applied Sciences

Subject: BIOMATERIALS
Code: 608017
Lecturer: Trần Hoài Khang PhD

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3.1. Introduction

3.2. Metallic and hybrid metal

3.3. Iron oxide magnetic particles

3.4. Nanoparticle of metal

3.5. Ceramic implant materials

3.6. Porous silica

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3.1. Introduction

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3.2. Metallic and hybrid metal

• Characteristics: high strength, resistance to fracture and corro-
sion.
• The advantages of metals over other materials such as ceram-
ics and polymers: strong, tough, and ductile (or
deformable, particularly as compared to ceramics)
Disadvantages: susceptibility to corrosion due to the nature of
the metallic bond (free electrons), a high density and much
greater stiffness than most natural materials they replace.
• Factors impacting on synthesis steps: final geometry of the
implant, the forming and machining properties of the metal,
and the costs of alternative fabrication methods.

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3.2. Metallic and hybrid metal

Elastic modulus of
currently used
biomedical alloys.

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3.2. Metallic and hybrid metal
(a) cytotoxicity of pure metals;
(b) relationship between polarization
resistance and biocompatibility of pure
metals, Co-Cr alloy and stainless steels

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3.2. Metallic and hybrid metal

CORROSION OF METALLIC IMPLANTS: an impor-
tant aspect
• Oxide of many metals: The lowest free energy state.
• The unwanted chemical reaction of a metal with its
environment  oxides, hydroxides, or other com-
pounds.
• The human body (water, dissolved oxygen, proteins,
and various ions such as chloride and hydroxide):
very aggressive to ionized metals.

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3.2. Metallic and hybrid metal

CORROSION OF METALLIC IMPLANTS

less oxygen: Fe3O4 (mag-

netite)
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CORROSION OF METALLIC IM-

PLANTS
The Nernst equation

R is the gas constant (8.314 J K−1 mol−1)

E0 is the standard electrochemical potential
T is the absolute temperature,
F is Faraday's constant (96,487 C/mole)
n is the number of moles of ions

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CORROSION OF METALLIC IMPLANTS

Two electrochemically dissim-

ilar metals in the same environ-
ment  bimetallic (or galvanic)
corrosion: more rapid than the
corrosion of a single metal.

Gold, platinum, and silver are

noble metals

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CORROSION OF METALLIC IMPLANTS

Galvanic action can also result in corrosion within a single

metal, if there is inhomogeneity in the metal or in its environ-
ment.

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CORROSION OF METALLIC IMPLANTS

Pourbaix Diagrams in Corrosion: a plot of regions of corro-

sion, passivity, and immunity as they depend on electrode poten-
tial and pH
• Corrosion region: > 10–6 gram atom per liter (molar) in
the solution at equilibrium.
• Immunity: equilibrium between metal and its ions at
less than 10–6 molar.
• Passivity: equilibrium between a metal and its reaction
products (oxides, hydroxides, etc.) at < 10–6 molar
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CORROSION OF METALLIC IMPLANTS

“oxy
gen”
lin e

“hyd
r ogen
” lin
e
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CORROSION OF METALLIC IMPLANTS

Rates of Corrosion and Polarization Curves
Potential–current
density curves for
some biomaterials.
An electric current
density: the number of
ions per unit time liber-
ated into the tissue - the
depth of metal removed
by corrosion in a given
time
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CORROSION OF METALLIC IMPLANTS

• Fatigue testing of implant materials:

The weight loss of a specimen of metal due to corrosion
is measured as a function of time.
Always be performed under physiological environmen-
tal conditions (Ringer's solution at body temperature).
Both repeated mechanical
loading and a chemically aggressive
environment: rubbing, pitting,
crevices (localized corrosion), …

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3.2. Metallic and hybrid metal

• Metals in current use as biomaterials : gold, cobalt chromium al-
loys, type 316 stainless steel, titanium, nickel-titanium alloys, and
silver-mercury amalgam (the most active (corrosion prone) mate-
rial).

• The noble metals (immune to corrosion): gold for dental restora-

tions (superior performance and longevity), not for orthopaedic
applications (high density, insufficient strength, high cost).

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3.2. Metallic and hybrid metal

• Titanium: passive under physiological conditions (corrosion cur-
rents in normal saline is 10-8 A/cm2); superior corrosion resistance
but not as stiff/strong as steel.

• Cobalt-chromium alloys: passive in human body, not pitting,

widely used for orthopaedic applications.

• Stainless steels: containing chromium to confer passive corrosion

(< Ti & Co-Cr) in human body; 316, 316L & 317 containing Mo.
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3.2. Metallic and hybrid metal

Experience in the orthopaedic setting with minimized corrosion:
1. Use appropriate metals.
2. Avoid implantation of different types of metal in the same region. In
the manufacturing process, provide matched parts from the same batch
of the same variant of a given alloy.
3. Design the implant to minimize pits and crevices.
4. In surgery, avoid transfer of metal from tools to the implant or tissue.
Avoid contact between metal tools and the implant, unless special care is
taken.
5. Recognize that a metal that resists corrosion in one body environment
may corrode in another part of the body.
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3.2. Metallic and hybrid metal

Experience in the dental setting with minimized corrosion:
1. Avoid using mixed metals to restore teeth in apposition, and if
possible, in the same mouth.
2. Use an insulating base when seating a metallic restoration to
minimize electrical conduction below the restoration.
3. Avoid conditions that lead to plaque buildup, since regions cov-
ered by plaque will experience reduced pH. This could result in
corrosion.

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3.3. Nanoparticle of metal

Gold Nanoparticles
Colloidal gold, also known as gold nanoparticles, is a suspen-
sion (or colloid) of nanometer-sized particles of gold.

The colloidal solution is either an intense red color (for parti-

cles less than 100 nm) or a dirty yellowish color (for larger parti-
cles)

Gold nanospheres with particle size around 10 nm in diameter

have a strong absorption maximum around 520 nm in aqueous so-
lution

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3.3. Nanoparticle of metal

Gold Nanoparticles

Sphere
The size varies
from 4 to 40 nm
(TEMs a-e)

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3.3. Nanoparticle of metal

Gold Nanoparticles

Rods
The aspect ratio
varies from 1.3 to 5
for short rods
(TEMs f-j) and 20
(TEM k) for long
rods

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3.3. Nanoparticle of metal

Gold Nanoparticles
Surface of gold nanoparticles can be easily modified to provide controlled release
strategies using internal or external stimuli such as glutathione, pH, heat, and
light.
Therapeutic agents can be loaded to gold nanoparticles by covalent or noncova-
lent interaction.
The kinetics and saturation concentrations are highly dependent on the physical
dimensions of the nanoparticles.
The nanoparticle size and shape can mediate receptor-ligand binding constants,
receptor recycling rates, and exocytosis.
Particles of size 1-2 nm were proved to be highly toxic.
Smaller gold compounds and larger gold nanoparticles (15 nm) were nontoxic ir-
respective of the cell type tested.
Chloroauric acid, and the precursor of gold NP synthesis including chloroauric
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acid, surfactant cetyl trimethyl ammonium bromide (CTAB) are toxic.
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3.3. Nanoparticle of metal

Gold Nanoparticles

Gold nanoshell
plasmon reso-
nances for a 120-
nm core with indi-
cated shell thick-
ness

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3.3. Nanoparticle of metal

Gold Nanoparticles

Formation of nanoshell dimer with the interaction of antibodies immobi-

lized on the surface of the nanoshells

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 TEM vs SEM

TEM offers valuable in-

formation on the inner
structure of the sample,
such as crystal structure,
morphology and stress
state information.

SEM provides information

on the sample’s surface
and its composition

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3.3. Nanoparticle of metal

Silver Nanoparticles
• Silver nanoparticles are the particles of silver, with particle
size between 1 and 100 nm.
• Like gold nanoparticles, ionic silver has a long history and
was initially used to stain the glass for yellow.
• Currently, there is also an effort to incorporate silver
nanoparticles into a wide range of medical devices, includ-
ing bone cement, surgical instruments, surgical masks, etc.
• Moreover, it has also been shown that ionic silver, in the
right quantities, is suitable in treating wounds.
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3.4. Iron oxide magnetic particles

Due to their ultrafine size, magnetic properties, and biocompat-
ibility, superparamagnetic iron oxide nanoparticles (SPION) have
emerged as promising candidates for various biomedical applica-
tions, such as enhanced resolution contrast agents for MRI, tar-
geted drug delivery and imaging, hyperthermia, gene therapy,
stem cell tracking, molecular/cellular tracking, magnetic separa-
tion technologies (e.g., rapid DNA sequencing) early detection of
inflammatory, cancer, diabetes, and atherosclerosis.
Ultrasmall particles of iron oxide (USPIO) (10–40 nm), small
particles of iron oxide (SPIO) (60–150 nm)

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3.5. Ceramic implant materials

Ceramics are refractory, polycrystalline compounds, usually inor-
ganic, including silicates, metallic oxides, carbides, and various refrac-
tory hydrides, sulfides, and selenides.
Oxides such as Al2O3, MgO, SiO2, etc. contain metallic and non-
metallic elements. Ionic salts (NaCl, CsCl, ZnS, etc.) can form poly-
crystalline aggregates, but soluble salts are not suitable for structural
biomaterials.
Diamond and carbonaceous structures like graphite and pyrolized
carbons are covalently bonded.

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3.5. Ceramic implant materials

Classification

simple cubic face-centered cubic

hexagonal close packing
AX structures of ceramics. The dark spheres represent positive
ions (A+) and the circled ones represent negative ions (X–).
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3.5. Ceramic implant materials

Physical Properties:
- Generally hard
- High melting temperature
- Low conductivity of electrictity and heat
- Be difficult to shear plastically.
- Brittle (non-ductile)
- Low tensile strength compared to the compressive strength

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3.5. Ceramic implant materials
ALUMINUM OXIDES (ALUMINA)

High hardness ~ low friction and wear.

Major advantages of using the alumina as joint replacement material in
spite of its brittleness
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3.5. Ceramic implant materials

ZIRCONIUM OXIDES (ZIRCONIA)

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3.5. Ceramic implant materials

Zirconia: low fric-
tion with articular
cartilage and excel-
lent biocompatibil-
ity;
The wear rate of zir-
conia–zirconia <<
alumina–alumina
combination: zirco-
nia for the femoral
head and socket.

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3.5. Ceramic implant materials

CALCIUM PHOS-
PHATE

more closely re-

lated to the mineral
phase of bone and
teeth; excellent
biocompatibility

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3.5. Ceramic implant materials

TEM photographs of hydroxyap-
atite crystals synthesized hy-
drothermally at 200ºC under 2
MPa for 5 hr:
(a) without additives, (b) KOH
(10 wt%) added, (c) K3PO4 (10 wt
%) added, and (d) EDTA (5 wt%)
added.
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3.5. Ceramic implant materials

Compact bone
~ 12-18 Gpa
Dentin ~21 GPa
Enamel ~74 GPa

Bone (~ 0.3)

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3.5. Ceramic implant materials

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3.5. Ceramic implant materials

Properties of Glass-Ceramics
Several desirable properties compared to glasses and ceramics
- The resistance to scratching and abrasion ~ sapphire
- The mechanical strength of the interfacial bond between bone
and Bioglass® ceramic is the same order of magnitude
The main drawback: brittleness
Not for making major load-bearing implants such as joint implants
due to restriction on the composition for biocompatibility (os-
teogenicity)
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3.5. Ceramic implant materials

Aging effect
on the
strength of
calcium alu-
minate in vitro
and in vivo.

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3.5. Ceramic implant materials

Structure of Carbons

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3.5. Ceramic implant materials

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3.5. Ceramic implant materials

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3.5. Ceramic implant materials

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3.6. Porous silica

Mesoporous silica nanoparticles (MSNs) have become apparent
as a promising and novel drug vehicle due to their unique meso-
porous structure that preserving a level of chemical stability, surface
functionality and biocompatibility ensure the controlled release, and
target drug delivery of a variety of drug molecules.
Mesoporous nanoparticles have a solid framework with porous
structure and large surface area, which allows the attachment of dif-
ferent functional group for targeted the drug moiety to a particular
site.

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3.6. Porous silica

Various pore geometrics of meso-

porous structure (a) 2D hexagonal
p6 mm, (b) bicontinuous cubic
Ia3d, (c) bicontinuous cubic pn3
m, (d) cage type pm3n, (e) cage
type Im3 m
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3.6. Porous silica

The mesoporous particle could be synthesized using a simple sol-
gel method or a spray drying method.
Synthetic amorphous silica consists of nano-sized primary particles
of nano or micrometer-sized aggregates and of agglomerates in the mi-
crometer-size range.
MSNs have been used in controllable drug delivery, gene transport,
gene expression, biomarking, biosignal probing, imaging agent, detect-
ing agent, drug delivery vehicles, and other important biological appli-
cations

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3.6. Porous silica

Biocompati
bility and bio-
distribution of
mesoporous
silica
nanoparticles

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3.6. Porous silica

Applications

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 Presentation

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Khi các mô bị tổn thương, thì cơ chế đông máu được khởi động bằng cả hai con đường bên
trong và bên ngoài. (intrinsic pathway & extrinsic pathway)
Sự phơi nhiễm của collagen dưới màng cứng kích hoạt yếu tố đông máu XII.
và yếu tố mô (một thụ thể cho yếu tố đông máu VII).
Kích hoạt tuần tự các yếu tố đông máu trong con đường bên trong và bên ngoài dẫn đến việc
tạo ra thrombin (yếu tố IIa)
để khởi động phản ứng tạo ra fibrin từ fibrinogen.
Các sản phẩm tiểu cầu, phospholipid từ các tế bào chết, ion Ca 2+ và nhiều yếu tố khác có liên
quan tại nhiều vị trí khác trong quá trình đông máu
và thrombin sinh ra tại vị trí đông máu tăng cường kích hoạt tiểu cầu.
Heparin tạo phức với yếu tố chống đông máu antithrombin III (AT); heparin-AT ức chế thrombin
và các yếu tố đông máu kích hoạt khác được liệt kê.
Heparin trọng lượng phân tử thấp (LMWH) và fondaparinux cũng tạo thành phức chất với AT tạo
thành phức chất để ức chế yếu tố Xa một cách chọn lọc.
Các thuốc xaban (như rivaroxaban, apixaban) là chất ức chế trực tiếp yếu tố Xa,

trong khi dabigatran và bivalirudin ức chế trực tiếp thrombin (yếu tố IIa).
Warfarin và các thuốc chống đông máu coumarin khác ức chế quá trình tổng hợp phụ thuộc vita-
min K của các yếu tố đông máu VII, IX, X và II (prothrombin) trong gan.

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