SYNTHETIC BIOMATERIALS AND POLYMERS IN MEDICINE

1. SYNTHETIC BIOMATERIALS AND POLYMERS IN MEDICINE

2. Material Science Logic Performance/Application Structure Synthesis Properties +processing • Physical • Biological

4. Biomaterials • Biomaterials are materials that are designed for in-vivo use • The study of biomaterials focuses on controlling/understanding the performance and interaction of synthetic or modified biological materials in biological systems, especially at the interface between synthetic and biological materials (biocompatibility)

5. A biomaterial is "any substance (other than drugs) or combination of substances synthetic or natural in origin, which can be used for any period of time, as a whole or as a part of a system which treats, augments, or replaces any tissue, organ, or function of the body".Biocompatibility — The ability of a material to perform with an appropriate host response in a specific applicationHost Response— The response of the host organism (local and systemic) to the implanted material or device.

6. Definitions • Biomaterial - Material for in-vivo use • Biocompatible - No adverse affects on biological system • Bioinert - No interaction with biological system • Bioerodable - Dissolves in biological system over time

7. Keywords • Metallic/glass/Polymeric/Ceramic/Composite • Fracture/fatigue/creep/corrosion/degradation • Tissue response/healing/biocompatibility/host response/carcinogenicity • Hard/soft tissue implants • Vascular/Breast/Urological/Art. Organ • Mucosal contacting …

8. Biomaterial Selection Parameters • Mechanical • Thermal/Electrical Conductivity • Diffusion • Water Absorption • Biostability • Biocompatibility

9. Biomaterial Selection Criteria • Specific Surface Interactions • Blood Contact • Need to Bear a Load • Structural Applications • Degradation Propensity • Permeability Responsiveness • Solubility under Physiological Conditions • Transparency Need • Bioenvironmental Responsiveness

10. Some Commonly Used Biomaterials MaterialApplications Silicone rubber Catheters, tubing Dacron Vascular grafts Cellulose Dialysis membranes Poly(methyl methacrylate) Intraocular lenses, bone cement Polyurethanes Catheters, pacemaker leads Hydogels Opthalmological devices, Drug Delivery Stainless steel Orthopedic devices, stents Titanium Orthopedic and dental devices Alumina Orthopedic and dental devices Hydroxyapatite Orthopedic and dental devices Collagen (reprocessed) Opthalmologic applications, wound dressings

11. Journals • Biomaterials • Biomaterials World News • Materials Today • Nature • Journal of Biomedical Materials Research • Cells and Materials • Journal of Biomaterials Science • Artificial Organs • ASAIO Transactions • Tissue Engineering • Annals of Biomedical Engineering • Medical Device Link • … see: http://www.biomat.net/biomatnet.asp?group=1_5

12. A Little History on Biomaterials • Chinese, Romans, and Aztecs used gold in dentistry over 2000 years ago, Cu not good. • Ivory & wood teeth • Aseptic surgery 1860 (Lister) • Bone plates 1900, joints 1930 • Turn of the century, synthetic plastics came into use • WWII, shards of PMMA unintentionally got lodged into eyes of aviators • Parachute cloth used for vascular prosthesis • 1960- Polyethylene (PE) and stainless steel being used for hip implants

13. Uses of Biomaterials • Replace diseased part – dialysis • Assist in healing – sutures • Improve function – contacts • Correct function – spinal rods • Correct cosmetic – nose, ear • Aid dx – probe • Aid tx – catheter • Replace rotten – amalgam • Replace dead - skin

14. Problems/test for w Biomaterials • Acute toxicity (cytotoxicity) arsenic • Sub chronic/chronic Pb • Sensitization Ni, Cu • Genotoxicity • Carcinogenicity • Reproductive &/or developmental Pb • Neurotoxicity • Immunotoxicity • Pyrogen, endotoxins

15. Evolution of Biomaterials Structural Soft Tissue Replacements Functional Tissue Engineering Constructs

16. Biomaterials for Tissue Replacements • Bioresorbable vascular graft • Biodegradable nerve guidance channel • Skin Grafts • Bone Replacements

17. Biomaterials - An Emerging Industry • Next generation of medical implants and therapeutic modalities • Interface of biotechnology and traditional engineering • Significant industrial growth in the next 15 years -- potential of a multi-billion dollar industry

18. Synthetic Biomaterial Classes • METALS: Co-Cr alloys, Stainless steels, Gold, Titanium alloys, Vitallium, Nitinol (shape memory alloys) Uses: orthopedics, fracture fixation,dental and facial reconstruction,stents • CERAMICS: Alumina, Zirconia, Calcium Phosphate, Pyrolitic Carbon Uses: orthopedics, heart valves, dental reconstruction • COATINGS: Bioglasses, Hydroxyapatite, Diamond-like carbon Uses: orthopedics, in-growth

19. Synthetic Biomaterial Classes cont. • POLYMERS: Silicones, Gore-tex (ePTFE), Polyethylenes(LDPE,HDPE,UHMWPE,) Polyurethanes, Polymethylmethacrylate,Polysulfone, Delrin Uses:orthopedics, artificial tendons,catheters, vascular grafts, facial and soft tissue reconstruction • COMPOSITES: CFRC, self reinforced, hybrids Uses:orthopedics, scaffolds • HYDROGELS: Cellulose, Acrylic co-polymers Uses:drug delivery, vitreous implants,wound healing • RESORBABLES: Polyglycolic Acid, Polylactic acid, polyesters Uses: sutures,drug delivery, in-growth, tissue engineering

20. Metals • Metals are (mostly) crystalline solids composed of elemental, positively charged ions in a cloud of electrons • Properties are a function of grain size, imperfections in crystal structure • Metals comprised of more than one element are alloys • The surface of metals are often oxides, if inert leads to protection, if active is corrosion • Typical metal properties include: • High melting points • High stiffness and strength • High conductivities • isotropic properties

21. Why Use Metals as Biomaterials • Properties and fabrication well known • Stiff and strong • Bioinert • Joining technologies known • Metals commonly used • Titanium • Stainless steel

22. Figure 4.1 These titanium-alloy joint replacements are an example of the many applications for metal biomaterials for implantations. (from http://www.spirebiomedical.com)

23. 金屬材料 (1).具有高強度及導電度等特性，在需要機械性強度或電傳導 ，則需使用金屬材料。 (2).如人工骨骼、關節及心臟節律器 (3).常用的金屬材料的種類及其應用列於表三 表三 金屬生醫材料及其應用

24. Ceramics • Ceramics are compounds characterized by ionic or covalent bonding • Ceramics are generally crystalline, crystalline SiO2 is quartz • Glasses are the amorphous “ceramics” common glass is amorphous SiO2 • Properties • Properties function of grain size, imperfections in crystal structure • Many ceramics comprised of more than one compound • Low conductivities (semi-conductors, insulators) • Stiff and Brittle

25. Why Use Ceramics as Biomaterials • Properties and fabrication well known • Stiff and strong • Bioinert • Obvious fix for teeth and bones

28. 陶瓷材料 (1).陶瓷材料是種無機非金屬固體，具有強的抗壓性質及很好 的生物相容性等優點，故常應用於生醫材料中 (2).常用的陶瓷材料的種類及其應用列於表四 表四 陶瓷類生醫材料及其應用

30. Metals Ceramics Polymers Semiconductor Materials Skin/cartilage Drug Delivery Devices Ocular implants Bone replacements Orthopedic screws/fixation Heart valves Synthetic BIOMATERIALS Dental Implants Dental Implants Biosensors Implantable Microelectrodes

31. 複合材料 (1).即几種材料，取其優點組合而成。 (2).一般而言，複合材料具生物相容性佳、抗腐蝕、高強度等 優點；其缺點是因為組合而成，故為不均質。 (3).常用的複合材料的種類及其應用列於表五。 表五 複合生醫材料及其應用

32. Issues • Understanding and controlling performance • Physical • Chemical • Biological • Relevant material performance is under biological conditions • 37 C, aqueous, saline, extracelluar matrix (ECM) • Material properties as a function of time • Initial negative biological response - toxicity • Long term biological response – rejection • Biology is a science of surfaces and interfaces • Seldom (never) at equilibrium

33. Materials Lessons from Biology Polymer based Nanoscaled Energy efficient Self-healing Ecologically sound Self-improving Smart! Biology represents a material/ part/system strategy that works

36. A Brief Introduction of Polymer A polymer is generally named based on the monomer it is synthesized from. For example, ethylene is used to produce poly(ethylene) (PE). For both glycolic acid and lactic acid, an intermediate cyclic dimer is prepared and purified, prior to polymerization. These dimers are called glycolide and lactide, respectively. Although most references in the literature refer to polyglycolide or poly(lactide), you will also find references to poly(glycolic acid) and poly(lactic acid). Poly(lactide) exists in two stereo forms, signified by d or l for dexorotary or levorotary, or by dl for the racemic mix. HOMOPOLYMER (one monomer)

37. Polymers • Terminology (contn): • copolymer: polymers of two mer types • random · · ·-B-A-B-A-B-B-A-· · · • alternating· · ·-A-B-A-B-A-B-A-· · · • block · · ·-A-A-A-A-B-B-B-· · · • heteropolymer: polymers of many mer types COPOLYMER

38. Polymers Structure Linear Branched Crosslinked

40. Polyurethanes A urethane has an ester group and amide group bonded to the same carbon. Urethanes can be prepare by treating an isocyanate with an alcohol. Polyurethanes are polymers that contain urethane groups.

42. I. Biodegradable Polymers PGA Tm= 225C Tg = 36C PLA Tm= 180C Tg = 60C PLGA Tg ~ 50 C PCL Tm= 61C Tg = -60C PPL Tm= 80C Tg = -24C

44. Biodegradable Synthetic Polymers Poly(alkylene ester)s PLA, PCL, PLGA Poly(aromatic/aliphatic ester)s Poly(amide-ester)s Poly(ester-urethane)s Polyanhydrides Polyphosphazenes Biostable Polymers Polyamides Polyurethanes Polyethylene Poly(vinylchloride) Poly(hydroxyethylmethacrylate) Poly(methylmethacrylate) Poly(tetrafluoroethylene) Poly(dimethyl siloxane) Poly(vinylalcohol) Poly(ethylenglycol) Synthetic Polymers Stimuli Responsive • Poly(ethylene oxide-co-propilene oxide) • Poly(methylvinylether) • Poly(N-alkyl acrylamide)s • Poly(phosphazone)s