CHAPTER Materials for

1 Biomedical
Applications

Biomaterials: Material intended to interface with biological systems

to evaluate, treat, augment, or replace any tissue, organ,
or function of the body
cf) Biological Materials

Biocompatibility
1. composition of biomaterials
2. fabrication process
3. implant production
1.1.2 History and Current Status of the Field

Plastics [poly(methylmethacrylate)] to Metal, Ceramic, Polymer

(1) Cardiovascular area

heart valve
synthetic vascular graft
(2) Artificial Joints
(3) Heart-lung machines

blood oxygenation limit

blood coagulation problem

(4) Renal dialysis

blood cell lysis

infection
immune response
1.1.3 Future Directions

inert biomaterials
bioactive materials

smart or instructive materials

injectable materials
nano-structured materials

Biomaterials for complete integration

and full reproduction of damaged tissue

1.2 Biological Response to Biomaterials

inflammation, immune response, blood clotting, infection, tumor formation,

implant calcification

Factors to be considered for biocompatibility

type of materials
shape of the implant
material degradation characteristics
surface chemical properties
bulk chemical and mechanical properties

the final location and application of the implant

protein and cellular response (in vitro and in vivo)

Endocytosis (pinocytosis and receptor-mediated endocytosis)

Phagocytosis (opsonin-mediated engulfing of microorganism)

a) Polymorphonuclear Leukocytes (PMN)
b) Macrophages
Kupffer cells, Alveolar macrophages, Splenic macrophages
Peritoneal macrophages, Microglial cells
c) Reticuloendothelial System (RES)
Macrophages in blood
Dendritic cells, Interdigitating cells, Langerhans cells
 (b) Extracellular Killing (Tc cell and NK cell)
NK cell via Killer cell inhibitory receptors (KIR)
NK cell activated by IL-2, IL-12, interferons

(4) Fever
pyrogens (IL-1 & IFN) from monocytes and macrophages

(5) Biologically Active Substances

degradative enzymes, toxic free radicals, acids, inhibitors of growth
acute-phase proteins, interferons
(6) Inflammation
swelling, redness, heat, pain, loss of function of the inflamed area
Injury – acute responses
a) localized inflammatory response
activation of the clotting, kinin-forming, and fibrolytic pathways
kinin ---- [smooth muscle contraction, distal muscle relaxation
vascular permeability, leukocyte extravasation,
pain (itching) perception]
b) systemic inflammatory response
fever, WBC, hydrocortisone and ACTH, acute-phase proteins
c) cytokines
IL-1, IL-6, TNF-a
[extravasation, coagulation, vascular permeability]
IL-8, IFN-g [chemotaxis, phagocytosis]
Accumulation of fluid (edema) and leukocytes
d) polymorphonuclear leukocytes and mononuclear cells
e) persisted infection
Ab and cell-mediated immunity
f) repairing the injury [macrophage-mediated]
g) chronic inflammation
[tuberculosis, rheumatoid arthritis, glomerulonephritis]
Acquired Immunity

humoral immunity: Ab from B-cell

cell-mediated immunity: T-cell and macrophage

immunization: active immunization

passive immunization
adoptive immunization

characteristics of the immune response

1. specificity
2. adaptiveness
3. discrimination between self and non-self
4. memory: anamnestic response
1.3 Biomaterial Product Testing and FDA Approval

Safe and effective

FDA approves devices, not materials

1.4 Types of Biomaterials

1.4.1 Metals
non-directional metallic bonds with highly mobile electrons
1.4.2 Ceramics
non-directional ionic bonds between electron donors and acceptors
--- hard and nondegradable but brittle

1.4.3 Polymers
directional covalent bonds

synthetic polymers
polymers from natural sources
1. Elastomers

2. Hydrogels

3. Composite materials

human tissues
1.4.4 Naturally Derived vs. Synthetic Polymers

Naturally Derived Polymers

1. full integration
2. easy remodeling
3. limited amount available
4. low mechanical properties
5. pathogenic contamination
6. immune response
7. biomaterials of decellularized tissue

Synthetic Polymers

1. mass production and sterilization

2. physical, chemical, mechanical, and degradative properties
3. no tissue interaction
4. low healing
5. low chance of human application
1.5 Processing of Biomaterials

(1) surface modification to alter the surface chemical and physical

properties
(2) shape

1.6 Important Properties of Biomaterials

1.6.1 Degradative properties

undesirable for implantation

desirable for certain materials (biodegradable materials)

1.6.2 Surface properties

chemical and physical properties

1.6.3 Bulk properties

(1) mechanical properties : strength and stiffness

anisotropy
fatigue property

(2) Physical properties

crystallinity
thermal transition

(3) Chemical properties

hydrophobicity

1.6.4 Characterization Techniques

Quantitative and Qualitative

1.7 Principles of Chemistry

1.7.1 Atomic structure

proton, neutron, electron
amu: atomic mass units

1.7.2 Atomic models

electrons: particle-like and wave-like qualities

1.7.3 Atomic Orbitals

Quantum numbers:
size, shape, and orientation of the electron probability functions

1. Principal quantum number

2. Azimuthal quantum number
3. Magnetic quantum number
4. Spin quantum number

(1) Shapes of subshells

(2) Order of subshells and the Aufbau principle

1. Lower energy states filled first

2. Pauli exclusion principle (two electrons with opposite spin)
3. Hund’s rule
1.7.4 Valence Electrons and the Periodic Table

Closed-shell configuration and open-shell configuration

Valence electrons: primary bonds like ionic and covalent bonds
1.7.5 Ionic Bonding

Bonding and Force-distance Curves

1.7.6 Covalent Bonding

(1) Atomic orbitals

and hybridization
 s and p bonds

(2) Molecular orbitals

(3) Mixed bonds

Ionic bonds ------------- Covalent bonds

1.7.7 Metallic Bonding

Electropositive elements without electronegative elements to accept electrons

Mobile electron cloud or sea

Electron sharing but non-directional
Mobility of electrons --- conductivity
1.7.8 Secondary Forces

Dipole-dipole interaction

Temporary (fluctuating) dipoles: van der Waals interaction

Permanent dipoles: hydrogen bonds