Biomaterials: an introduction

Li Jianguo
Jianguo.li@stamariawater.se
Tel: 08-711 0888
Fax: 08-7740638
Jianguo.li@stamariawater.se
Evolution of Biomaterial Science
& Technology
• 1st generation (since 1950s)
Goal: Bioinertness
• 2nd generation (since 1980s)
Goal: Bioactivity
• 3rd generation (since 2000s)
Goal: Regenerate functional tissue
 Some application of biomaterials
Application
• Skeletel system
• Joint replacement(Hip, knee)
• Bone plate
• Bone cement
• Artificial tendon and ligment
• Dental implant
• Cardiovascalar sysem
• Blood vessel prosthesis
• Heart valve
• Catheter
• Organs
• Artificial heart
• Skin repair template
• Artificial kidney
• Heart-lung machine
• Senses
• Cochlear replacement
• Intraocular lens
• Contact lens
• Corneal bandage
Types of Materials
• Titanium , Stainless steel, PE
• Stainless steel, Co-Cr alloy
• PMMA
• Hydroxylapatie Teflon, Dacron
• Titanium, alumina, calcium phosphate
• Dacron, Teflon, Polyurethane
• Reprocessed tissue, Stainless steel, Carbon
• Silicone rubber, teflon, polyurethane
• Polyurethane
• Silicone-collage composite
• Cellulose, polyacrylonitrile
• Silicone rubber
• Platium electrodes
• PMMA, Silicone rubber, hydrogel
• Silicone-acrylate. Hydrogel
• Collagen, hydrogel
 What is a Biomaterial?
A material intented to interface with
biological systems to evaluate, treat,
augment or replace any tissue, organ
or function of the body.
 Biomaterials
• Polymeric biomaterials
• Bioceramics
• Metallic biomaterials
• Biocomposite
• Biologically based (derived) biomaterials
 Biocompatibility
• Biocompatibility: The ability of a material
to perform with an appropriate host
response in a specific application.
• Host response: the reaction of a living
system to the presence of a material
 Biocompatibility
• B=f(X1,X2......Xn)
• Where X: material, design, application etc.
 Medical Device
• It does not achieve its principal intended
action in or on the human body by
pharmacological, immunological or
metabolic means, but it may be assisted in
its function by such means.
 Polymerization
• Condensation: A reaction occurs between
two molecules to form a larger molecule
with the elimination of a smaller molecule.
• Addition: A reaction occurs between two
molecules to form a larger molecule
without the elimination of a smaller
molecule.
 Polymeric Biomaterials: Adv &
Disadv
• Easy to make complicated • Leachable compounds
items • Absorb water & proteins
• Tailorable physical & etc.
mechanical properties • Surface contamination
• Surface modification • Wear & breakdown
• Immobilize cell etc. • Biodegradation
• Biodegradable • Difficult to sterilize
 Polymeric Biomaterials
• PMMA
• PVC
• PLA/PGA
• PE
• PP
• PA
• PTFE
• PET
• PUR
• Silicones
 Bioceramic: Advantages and
disadvantage
• High compression • High modulus
strength (mismatched with bone)
• Wear & corrosion • Low strength in tension
resistance • Low fracture toughness
• Can be highly polished • Difficult to fabricate
• Bioactive/inert
 Bioceramics
• Alumina
• Zirconia (partially stabilized)
• Silicate glass
• Calcium phosphate (apatite)
• Calcium carbonate
Metallic Biomaterials:Advantages & Disadvantages

• High strength • High moduls

• Fatigue resistance • Corrosion
• Wear resistance • Metal ion sensitivity
• Easy fabrication and toxicity
• Easy to sterilize • Metallic looking
• Shape memory
 Metallic biomaterials
• Stainless steel (316L)
• Co-Cr alloys
• Ti6Al4V
• Au-Ag-Cu-Pd alloys
• Amalgam (AgSnCuZnHg)
• Ni-Ti
• Titanium
Surface modification (treatment)
• Physical and mechanical treatment
• Chemical treatment
• Biological treatment
 Surface Properties of Materials
• Contact angle (Hydrophilic & Hydrophobic)
• ESCA & SIMS (surface chemical analysis)
• SEM (Surface morphology)
 Deterioration of Biomaterials
• Corrossion
• Degradation
• Calcification
• Mechanical loading
• Combined
 General Criteria for materials
selection
• Mechanical and chemicals properties
• No undersirable biological effects
carcinogenic, toxic, allergenic or
immunogenic
• Possible to process, fabricate and sterilize
with a godd reproducibility
• Acceptable cost/benefit ratio
 Material Properties
• Compresssive strength • Surface tension
• Tensile strength • Hardness and density
• Bending strength • Hydrophobic/philic
• E-Modulus • Water
• Coefficient of thermal sorption/solubility
expansion • Surface friction
• Coefficient of thermal • Creep
coductivity • Bonding properties
 Cell/tissue reaction to implant
• Soft tissue
• Hard tissue
• Blood cells
 The biological milieu
• Atomic scale
• Molecular scale
• Cellular level
• Tissue
• Organ
• System
• Organism
 pH in humans
• Gastric content 1.0
• Urine 4.5-6.0
• Intracellular 6.8
• Interstitial 7.0
• Blood 7.17-7.35
 Sequence of local events following
implantation in soft tissue
• Injury
• Actute inflammation
• Granulation tissue
• Foreign body reaction
• fibrosis
Soft tissue response to an implant
• Actut (mins to hrs)
Cell type: Leukocytes
Function: Recognition, engulfment and degradation (killing)
• Chronic (days to months)
Cell types: Macrophages, monocytes and lymphocytes.
• Granulation tissue formation (3-5 days)
Cell types: Endothelial cells (forming blood vesssels), fibeoflasts
(forming connnective tissue)
• Foreign body reaction (days to life time)
Cell types: Foreign body giant cells, Macrophages, fibroblasts
• Fibrosis & Fibrous encapsulation
Cell type: Fibroblasts
 Bioactive and Osteointegration
• A chemical bonding between bone and
material will be formed. (Bioactive,
Hydroxylapatite)

• A direct contact between bone and impant

under light microscope. (Osterintegration,
titanium)
 Blood material interaction
• Hemolysis (red cells)
• Coagulation (Platelets)
 Test Hierarchies (for blood-contacting device)
• Cell culture, cytotoxicity (Mouse L929 cell line)
• Hemolysis (rabbit or human blood)
• Mutagenicity (Ames test)
• Systemic injection, acute toxicity (Mouse)
• Sensitization (Guinea pig)
• Pyrogenicity (Rabbit)
• Intramuscular implnatation (Rat, rabbit)
• Blood compatibility
• Long-term implatation.
 Standards
• Test methods
• Materials standards
• Device standards
• Procedure standards
 ISO 10993 and EN 30993
• ISO 10993-1: guidance on selection of tests
• ISO 10993-2: Animal welfare requirements
• ISO 10993-3: Test for genotoxicity, carcinogenicity and reproductive toxicity
• ISO 10993-4: Selection of tests for interactions with blood
• ISO 10993-5: Tests for cytotoxicity: In vitro methods
• ISO 10993-6: Test for local effects after implantation
• ISO 10993-7: Ethylene oxide sterilization residuals
• ISO 10993-8: Clinical investigation
• ISO 10993-9: Degradation of materials related to biological testing
• ISO 10993-10: Tests for irritation and sensitization
• ISO 10993-11: Tests for systemic toxicity
• ISO 10993-12: Sample preparation and reference materials
• ........
 Testing of Biomaterials
• Physical and mechanical
• Biological
In vitro assessment
in vivo assessment
Functional assessment
Clincal assessment
 Biomaterials applications
• Dental implant
• Tooth fillings
• Vascular implants
• Drug delivery, bone fixing pine, suture
• Bone defect fillings
• Hip joint prosthesis bone plate
• Scaffolds for tissue engineering
• Contanct lens
 3-principles in dental implant
design
• Initial retention
• Anti-rotation mechanics
• No sharp-edges
 Tooth fillings materials
• Amalgam
• Dental composite
• Ceramics
• Other metals
 General criteria for tooth filling
materials
• Non-irritation to pulp and gingival
• Low systemic toxicity
• Cariostatic
• Bonding to tooth substance without marginal leakage (20 u)
• Not dissolved or erode in saliva
• Mechanical strength, wear resistance, modules matching.
• Good aesthetic properties
• Thermal propertiesy (expansion & conductivity)
• Minimal dimensional changes on setting and adequate working time
and radio opacity
 Textile structure and vascular implant

• Weaving
• Braiding
• knitting
 Calcium phosphate-based
bioceramic
• Bone (ACP, DCPD, OCP &HA)
• Ca-P compounds
• Applications:
Bone fillers/HA-coatings/HA-PLA/In situ setting cement/tooth
paste/drug tablets
 Hip joint prosthesis
• Ceramic head
• Metallic stem
• Polymeric socket
• Composite bone cement
 Tissue engineering
• The application of engineering disciplines to either
maintain existing tissue structures or ti enable tissue
growth.
• From a material engineering pint of view, tissues are
considered to be cellular composites representing mltiphase
system:
Three main structural components:
1. Cells organised into functional units
2. The extracellular matrix
3. Scaffolding architecture
 Polymer concepts in tissue engineering

• Fabrication procedures of a porous polymer

3D scaffold:
PLGA dissolved in chloroform and
mixed with NaCl particles, evaporation of
the chloroform, dissoltion of NaCl in water,
resulting a polymer sponge with over 96%
porosity.
 Requirements for Soft Tissue
Adhesive
• Biodegradable
• Fast spread on wet (wound) surface
• Adequate working time
• Adequate bonding strength
• Hemostasis
• Biocompatible
 Contact lens
• Optical properties
• Chemical stability
• Oxygen transmissibility
• Tear film wettability
• Resistance to lipid/protein deposition
• Easy to clean
 Drug delivery (Slow/Controlled
release)
• Most effective and low toxi dose
• A constant dosage over a long period
• Local treatment
• Easy to handle and cost-effective
 Classification of slow release
system
• Diffusion controlled
• Water penetration controlled
• Chemically controlled
• Pendant chain systems
• Regulated system (Magnetic or ultrasound)
Leading medical device company
• Johnson & Johnson (www.jnj.com)
• Biomet INC (www.biomed.com)
• Strycker Howmedica Osteonics (www.osteonis.com)
• Sulzer Orthopedics Ltd (www.sulzerotho.com)
• Zimmer (www.zimmer.com)
• Merck & Co Inc (www.merck.com)
• Nobel biocare/AstraZeneca/Pacesetter AB/Q-med/Artimplant/Doxa
 Sterilization Methods
•Moist heat (121-125oC, 15-30 min)
•EO (CH2CH2O)
•Radiation (60Co & Electron Beam)
•Dry heat > 140oC
•Others (UV, Ozone X-ray etc)
 Silicone Applications
•Orthopedics (small joints)
•Catheters, Drains
•Extracorpreal Equipment (Dialysis,
heart bypass manchines, blood oxygenator)

•Aesthetic implant
•Spine
•HIP ?
Calcium phosphate cement (CPC) is a synthetic bone graft material that was invented
in 1986 by L. C. Chow and W. E. Brown, scientists at the American Dental
Association. The cement is a white powder consisting of equimolar amounts of ground
Ca4(PO4)2O (tetracalcium phosphate, TTCP) and CaHPO4 (dicalcium phosphate
anhydrous, DCPA). When mixed with water, the material forms a workable paste
which can be shaped during surgery to fit the contours of a wound. The cement
hardens within 20 min allowing rapid closure of the wound. The hardening reaction,
which forms nanocrystalline hydroxyapatite (HA) as the product, is isothermic and
occurs at physiologic pH so tissue damage does not occur during the setting reaction.
CPC was FDA approved for the treatment of non-load-bearing bone defects in 1996.
HA is the primary inorganic component of natural bone which makes the hardened
cement biocompatible and osteoconductive. Over time, CPC is gradually resorbed
and replaced with new bone. Because CPC is brittle, it is used for non-load-bearing
applications such as dental and cranio-facial applications. CPC has two significant
advantages over pre-formed, sintered ceramics. First, the CPC paste can be sculpted
during surgery to fit the contours of the wound. Second, the nanocrystalline
hydroxyapatite structure of the CPC makes it osteoconductive causing it to be
gradually resorbed and replaced with new bone. Recent work with CPC has focused
on improving mechanical properties, making premixed cements, making the cement
macroporous and seeding cells and growth factors into the cement.
Invention of CPC: Brown WE, Chow LC (1986) A new calcium phosphate water
setting cement. Brown PW, ed. Cements Research Progress. Westerville, OH:
American Ceramic Society; 352–379.
CPC Review: Friedman CD, Costantino PD, Takagi S, Chow LC. (1998)
BoneSourceTM hydroxyapatite cement: a novel biomaterial for craniofacial skeletal
tissue engineering and reconstruction. J Biomed Mater Res (Appl Biomater) 43:428-
432, 1998.
Image Copyright 2007 by Wright Medical Technology, Inc. Used with permission.
 Requirements of a Scaffold used
for tissue engineering
• Easy cell penetration, distribution, proliferation
• Permeability of culture medium
• In vivo vascularization (once implanted)
• Maintenance of cell phenotypes
• Adequate mechanical properties
• Controlled biodegradation
• Ease of fabrication