1. Biomaterials: an introduction
Li Jianguo
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2. 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

3. Some application of biomaterials
Types of Materials
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
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

4. 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.

5. Biomaterials Polymeric biomaterials Bioceramics Metallic biomaterials
Biocomposite
Biologically based (derived) biomaterials

6. 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

7. Biocompatibility B=f(X1,X2......Xn)
Where X: material, design, application etc.

8. 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.

9. 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.

10. Polymeric Biomaterials: Adv & Disadv
Easy to make complicated items
Tailorable physical & mechanical properties
Surface modification
Immobilize cell etc.
Biodegradable
Leachable compounds
Absorb water & proteins etc.
Surface contamination
Wear & breakdown
Biodegradation
Difficult to sterilize

11. Polymeric Biomaterials
PMMA
PVC
PLA/PGA PE PP PA
PTFE
PET
PUR
Silicones

12. Bioceramic: Advantages and disadvantage
High compression strength
Wear & corrosion resistance
Can be highly polished
Bioactive/inert
High modulus (mismatched with bone)
Low strength in tension
Low fracture toughness
Difficult to fabricate

13. Bioceramics Alumina Zirconia (partially stabilized) Silicate glass
Calcium phosphate (apatite)
Calcium carbonate

14. Metallic Biomaterials:Advantages & Disadvantages
High strength
Fatigue resistance
Wear resistance
Easy fabrication
Easy to sterilize
Shape memory
High moduls
Corrosion
Metal ion sensitivity and toxicity
Metallic looking

15. Metallic biomaterials
Stainless steel (316L)
Co-Cr alloys
Ti6Al4V
Au-Ag-Cu-Pd alloys
Amalgam (AgSnCuZnHg)
Ni-Ti
Titanium

16. Surface modification (treatment)
Physical and mechanical treatment
Chemical treatment
Biological treatment

17. Surface Properties of Materials
Contact angle (Hydrophilic & Hydrophobic)
ESCA & SIMS (surface chemical analysis)
SEM (Surface morphology)

18. Deterioration of Biomaterials
Corrossion
Degradation
Calcification
Mechanical loading
Combined

19. 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

20. Material Properties Compresssive strength Tensile strength
Bending strength
E-Modulus
Coefficient of thermal expansion
Coefficient of thermal coductivity
Surface tension
Hardness and density
Hydrophobic/philic
Water sorption/solubility
Surface friction
Creep
Bonding properties

21. Cell/tissue reaction to implant
Soft tissue
Hard tissue
Blood cells

22. The biological milieu Atomic scale Molecular scale Cellular level
Tissue
Organ
System
Organism

23. pH in humans Gastric content 1.0 Urine 4.5-6.0 Intracellular 6.8
Interstitial
Blood

24. Sequence of local events following implantation in soft tissue
Injury
Actute inflammation
Granulation tissue
Foreign body reaction
fibrosis

25. 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

26. 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)

27. Blood material interaction
Hemolysis (red cells)
Coagulation (Platelets)

28. 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.

29. Standards Test methods Materials standards Device standards
Procedure standards

30. ISO 10993 and EN 30993 ISO 10993-1: guidance on selection of tests
ISO : Animal welfare requirements
ISO : Test for genotoxicity, carcinogenicity and reproductive toxicity
ISO : Selection of tests for interactions with blood
ISO : Tests for cytotoxicity: In vitro methods
ISO : Test for local effects after implantation
ISO : Ethylene oxide sterilization residuals
ISO : Clinical investigation
ISO : Degradation of materials related to biological testing
ISO : Tests for irritation and sensitization
ISO : Tests for systemic toxicity
ISO : Sample preparation and reference materials

31. Testing of Biomaterials
Physical and mechanical
Biological
In vitro assessment
in vivo assessment
Functional assessment
Clincal assessment

32. 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

33. 3-principles in dental implant design
Initial retention
Anti-rotation mechanics
No sharp-edges

34. Tooth fillings materials
Amalgam
Dental composite
Ceramics
Other metals

35. 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

36. Textile structure and vascular implant
Weaving
Braiding
knitting

37. 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

38. Hip joint prosthesis Ceramic head Metallic stem Polymeric socket
Composite bone cement

39. 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

40. 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.

41. Requirements for Soft Tissue Adhesive
Biodegradable
Fast spread on wet (wound) surface
Adequate working time
Adequate bonding strength
Hemostasis
Biocompatible

42. Contact lens Optical properties Chemical stability
Oxygen transmissibility
Tear film wettability
Resistance to lipid/protein deposition
Easy to clean

43. 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

44. Classification of slow release system
Diffusion controlled
Water penetration controlled
Chemically controlled
Pendant chain systems
Regulated system (Magnetic or ultrasound)

45. Leading medical device company
Johnson & Johnson (
Biomet INC (
Strycker Howmedica Osteonics (
Sulzer Orthopedics Ltd (
Zimmer (
Merck & Co Inc (
Nobel biocare/AstraZeneca/Pacesetter AB/Q-med/Artimplant/Doxa

46. Sterilization Methods
Moist heat ( oC, min)
EO (CH2CH2O)
Radiation (60Co & Electron Beam)
Dry heat > 140oC
Others (UV, Ozone X-ray etc)

47. Silicone Applications
Orthopedics (small joints)
Catheters, Drains
Extracorpreal Equipment (Dialysis, heart bypass manchines, blood oxygenator)
Aesthetic implant
Spine
HIP ?