1. Biomaterials1 Introduction to Biomedical Engineering Week 6 Mar. 25 th 2014 Introduction to Biomaterials Ming-Long Yeh 葉明龍 mlyeh@mail.ncku.edu.tw Phone: 63429

2. Biomaterials2 References Biomaterials Science: An Introduction to Materials in Medicine Biomaterials Science: An Introduction to Materials in Medicine By: Ruddy D. Ratner; Allan Hoffman; Frederick Schoen and Jack Lemons Biomaterials Biomaterials by Sujata Bhat Introductory to Biomedical Engineering Introductory to Biomedical Engineering by Enderle, Blanchard, and Bronzino 生物醫學材料 生物醫學材料 by 王盈錦

3. Biomaterials3 Outline Biomaterials: Biomaterials: Introduction Introduction Classic Examples Classic Examples Characteristics of Biomaterials Science Characteristics of Biomaterials Science Subjects Integral to Biomaterials Science Subjects Integral to Biomaterials Science A History of Biomaterials A History of Biomaterials Classification of Materials: Construction materials Classification of Materials: Construction materials Impact of biomaterials Impact of biomaterials Strength of biological tissues Strength of biological tissues Performance of implants Performance of implants Tissue response to implants Tissue response to implants Properties of Materials Properties of Materials Interfacial phenomena Interfacial phenomena Properties of Materials Properties of Materials

4. Biomaterials4 Introduction Definition: Biomaterial (1987, Williams) A biomaterial is a nonviable material used in a medical device, intended to interact with biological system. (1987, Williams) A biomaterial is a nonviable material used in a medical device, intended to interact with biological system. (Bhat) Any nondrug material that can be used to treat, enhance or replace any tissue, organ, or function in a organism. (Bhat) Any nondrug material that can be used to treat, enhance or replace any tissue, organ, or function in a organism. (Bhat) Biological derived material that is used for its structural rather than its biological properties (Bhat) Biological derived material that is used for its structural rather than its biological properties

5. Biomaterials5 Introduction Biomaterial( Merriam-Webster ) Materials used for or suitable for used in prostheses that comes in direct contact with living tissues. Materials used for or suitable for used in prostheses that comes in direct contact with living tissues. A natural or synthetic material (as a polymer or metal) that is suitable for introduction into living tissue especially as part of a medical device (as an artificial heart valve or joint) A natural or synthetic material (as a polymer or metal) that is suitable for introduction into living tissue especially as part of a medical device (as an artificial heart valve or joint) Material used to construct artificial organs, rehabilitation devices, or prostheses and replace natural body tissues. Material used to construct artificial organs, rehabilitation devices, or prostheses and replace natural body tissues. A synthetic material, usually a plastic, suitable for implanting in a living body to repair damaged or diseased parts. A synthetic material, usually a plastic, suitable for implanting in a living body to repair damaged or diseased parts.

6. Biomaterials6 Biocompatibility Biocompatibility: in the ability of a material to perform with an appropriate host response in a specific application Biocompatibility: in the ability of a material to perform with an appropriate host response in a specific application Good biocompatibility is achieved when the material exists within a living body without adversely or significantly affecting it or being affected by it. Good biocompatibility is achieved when the material exists within a living body without adversely or significantly affecting it or being affected by it.

7. Biomaterials7 Introduction to Biomaterials Biomaterials used in medical devices, provide needs in such diverse surgical disciplines as Biomaterials used in medical devices, provide needs in such diverse surgical disciplines as ophthalmology, ophthalmology, cardiology, cardiology, neuromuscular surgery, neuromuscular surgery, orthopedics and orthopedics and dentistry. dentistry. All biomaterials have one thing in common; they must have intimate contact with patient’s tissue or body fluid, providing a real physical interface. All biomaterials have one thing in common; they must have intimate contact with patient’s tissue or body fluid, providing a real physical interface.

8. Biomaterials8 Introduction The material should have adequate mechanical strength, chemical and physical properties. The material should have adequate mechanical strength, chemical and physical properties. Thus biomaterials must be compatible with body tissues mechanically, chemically as well as pharmacologically. Thus biomaterials must be compatible with body tissues mechanically, chemically as well as pharmacologically.

9. Biomaterials9 Introduction To research these materials the investigator need to have arrange of techniques for To research these materials the investigator need to have arrange of techniques for materials production, materials production, measurement of strength and surface properties and measurement of strength and surface properties and in vitro and in vivo techniques for biocompatibility evaluation. in vitro and in vivo techniques for biocompatibility evaluation.

10. Biomaterials10 Introduction The functions of implants fall into one the following categories: The functions of implants fall into one the following categories: Load bearing or transmission; Load bearing or transmission; The control of fluid flow in order to stimulate normal physiological function or situation; The control of fluid flow in order to stimulate normal physiological function or situation; Passive space filling either for cosmetic reasons or functional reasons; Passive space filling either for cosmetic reasons or functional reasons; Generation of electric stimuli and transmission of light and sound. Generation of electric stimuli and transmission of light and sound.

11. Biomaterials11 Introduction Although biomaterials primarily used in medical application, it was also used to grow cells in culture, in apparatus for handling protein in laboratory, devices to regulate fertility in cattle, in aquaculture of oyster, cell-silicon “biochip”. Although biomaterials primarily used in medical application, it was also used to grow cells in culture, in apparatus for handling protein in laboratory, devices to regulate fertility in cattle, in aquaculture of oyster, cell-silicon “biochip”. Biomaterials are rarely used as simple materials, integrated into devices (final fabricated, sterilized form) Biomaterials are rarely used as simple materials, integrated into devices (final fabricated, sterilized form)

12. Biomaterials12 Introduction Some applications of biomaterials Some applications of biomaterials Skeletal system Skeletal system Cardiovascular system Cardiovascular system Organs Organs Senses Senses

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16. Biomaterials16 Classic Examples: Heart valve prostheses Heart valve prostheses: Heart valve prostheses are fabricated from carbons, metals, elastomers, fabrics and natural (e.g. pig) valves and Heart valve prostheses: Heart valve prostheses are fabricated from carbons, metals, elastomers, fabrics and natural (e.g. pig) valves and other tissues chemically pretreated to reduce their immunologic reactivity and enhance durability. other tissues chemically pretreated to reduce their immunologic reactivity and enhance durability. Problem: degeneration of tissue, mechanical failure, postoperative infection, and induction of blood clot. Problem: degeneration of tissue, mechanical failure, postoperative infection, and induction of blood clot. Carbon Metal Elastomer Fabricates

17. Biomaterials17 Classic Examples: Artificial Hip Joint Artificial Hip Joint: The human hip joint is subjected to high mechanical stress and undergoes considerable abuse. Artificial Hip Joint: The human hip joint is subjected to high mechanical stress and undergoes considerable abuse. Hip joints are fabricated from specific high-strength alloy, ceramics, composites, and ultrahigh molecular weight polyethylene. Hip joints are fabricated from specific high-strength alloy, ceramics, composites, and ultrahigh molecular weight polyethylene. good function is restored even athletic activities are possibleIn most cases, good function is restored, and even athletic activities are possible. loosenAfter 10-15 years, the implant may loosen, necessitating another operation.

18. Biomaterials18 Classic Examples: Dental implant Dental implant: Titanium implants, which form an artificial tooth root on which crown is affixed. Dental implant: Titanium implants, which form an artificial tooth root on which crown is affixed. A special requirement of a material in this application is the ability to form a tight seal against bacterial invasion where the implant traverses the gingival (gum ). A special requirement of a material in this application is the ability to form a tight seal against bacterial invasion where the implant traverses the gingival (gum ).

19. Biomaterials19 Classic Examples: Intraocular Lenses Intraocular Lenses 人工水晶體 : Intraocular Lenses (IOLs) made by poly (methyl methacrylate), silicone elastomer, or other materials are used to replaced a natural lens when it become cloudy and cataractous. 白內障 Intraocular Lenses 人工水晶體 : Intraocular Lenses (IOLs) made by poly (methyl methacrylate), silicone elastomer, or other materials are used to replaced a natural lens when it become cloudy and cataractous. 白內障 http://www.allaboutvision.com/conditions/iols.htm

20. Biomaterials20 Classic Examples: A broad range of synthetic materials varying in chemical, physical, and mechanical properties are used in the body. A broad range of synthetic materials varying in chemical, physical, and mechanical properties are used in the body. Many anatomical sites are involved. Many anatomical sites are involved.

21. Biomaterials21 Characteristics of Biomaterials Science Many Materials: A wide range of materials ( metals, ceramics, polymers, and natural materials ) is routinely used and no one researcher will be comfortable synthesizing and designing with all these materials. Many Materials: A wide range of materials ( metals, ceramics, polymers, and natural materials ) is routinely used and no one researcher will be comfortable synthesizing and designing with all these materials. Thus, specialization is the rule. However, a board appreciation of the properties and application of theses materials is a hallmark of professional in the field. Thus, specialization is the rule. However, a board appreciation of the properties and application of theses materials is a hallmark of professional in the field.

22. Biomaterials22 Characteristics of Biomaterials Science Hard tissue replacement biomaterials: metals, ceramics, used in orthopedic and dental materials. Hard tissue replacement biomaterials: metals, ceramics, used in orthopedic and dental materials. Soft tissue replacement biomaterials: polymers, cardiovascular and general plastic surgery materials. Soft tissue replacement biomaterials: polymers, cardiovascular and general plastic surgery materials. Some devices involved both soft and hard tissue. There is need for a general understanding of all class of materials. Some devices involved both soft and hard tissue. There is need for a general understanding of all class of materials.

23. Biomaterials23 Characteristics of Biomaterials Science Development of biomaterials devices: Fig 6. It provides a perspective on how different disciplines work together, starting from the It provides a perspective on how different disciplines work together, starting from the identification of a need for a biomaterial, identification of a need for a biomaterial, materials synthesis, materials synthesis, materials testing, materials testing, (ASTM: American Society for Testing Materials) fabrication, fabrication, sterilization and packaging, sterilization and packaging, device testing, device testing, regulatory, regulatory, clinical use, and clinical use, and explant analysis explant analysis

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27. Biomaterials27 Characteristics of Biomaterials Science Magnitude of the field. Magnitude expresses both a magnitude of need and magnitude of a commercial market. Magnitude of the field. Magnitude expresses both a magnitude of need and magnitude of a commercial market. Needless to say, a conflict of interest can arise with pressure from both the commercial quarter and from the ethical consideration. Needless to say, a conflict of interest can arise with pressure from both the commercial quarter and from the ethical consideration. The market of health care and biomaterials in US: Table 2 The market of health care and biomaterials in US: Table 2

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31. Biomaterials31 Subjects Integral to Biomaterials Science Toxicology Toxicology Biocompatibility Biocompatibility Healing Healing Unique anatomical site Unique anatomical site Mechanical and Performance requirements Mechanical and Performance requirements Industrial involvement Industrial involvement Ethics concerns Ethics concerns Regulation Regulation

32. Biomaterials32 Subjects Integral to Biomaterials Science Toxicology: It deals with the substances that migrate out of biomaterials. Ex: for polymers, many low-molecular-weight “leachables” exhibit some level of physiologic activity and cell toxicity. Toxicology: It deals with the substances that migrate out of biomaterials. Ex: for polymers, many low-molecular-weight “leachables” exhibit some level of physiologic activity and cell toxicity. It is reasonable to say that a biomaterial should not give off anything from its mass unless it is specifically designed to do so. It is reasonable to say that a biomaterial should not give off anything from its mass unless it is specifically designed to do so.

33. Biomaterials33 Subjects Integral to Biomaterials Science Biocompatibility: The understanding and measurement of biocompatibility is unique to biomaterials science. Biocompatibility: The understanding and measurement of biocompatibility is unique to biomaterials science. Unfortunately, we do not have precise definitions or accurate measurements of biocompatibility. Unfortunately, we do not have precise definitions or accurate measurements of biocompatibility. It is defined in terms of performance or success at a specific task. It is defined in terms of performance or success at a specific task. However, this operational definition offers us little to use in designing new or improved vascular prostheses. However, this operational definition offers us little to use in designing new or improved vascular prostheses. In fact, biocompatibility may have to be uniquely defined for each application. In fact, biocompatibility may have to be uniquely defined for each application.

34. Biomaterials34 Subjects Integral to Biomaterials Science Healing: Injury to tissue will stimulate the well define inflammatory reaction sequence that lead to healing. Healing: Injury to tissue will stimulate the well define inflammatory reaction sequence that lead to healing. When a foreign body is involved, the reaction sequence is referred to as “foreign body reaction”. When a foreign body is involved, the reaction sequence is referred to as “foreign body reaction”. The normal response of body will be modulated because of the solid implant. The normal response of body will be modulated because of the solid implant. This reaction will differ in intensity and duration depending upon the anatomical sites involved. This reaction will differ in intensity and duration depending upon the anatomical sites involved.

35. Biomaterials35 Subjects Integral to Biomaterials Science Unique anatomical site: Each site challenges the biomedical device designer with special requirements for geometry, size, mechanical properties, and bioreaction. Unique anatomical site: Each site challenges the biomedical device designer with special requirements for geometry, size, mechanical properties, and bioreaction.

36. Biomaterials36 Subjects Integral to Biomaterials Science Mechanical and Performance requirements: Each biomaterial and device has imposed upon in mechanical and performance requirements that originate from the physical (bulk) properties of the material. Mechanical and Performance requirements: Each biomaterial and device has imposed upon in mechanical and performance requirements that originate from the physical (bulk) properties of the material. These requirements can be divided into three categories: These requirements can be divided into three categories: mechanical performance, mechanical performance, mechanical durability, and mechanical durability, and physical properties (functional). physical properties (functional).

37. Biomaterials37 Subjects Integral to Biomaterials Science Industrial involvement: The balance between the desire to alleviate loss of life and suffering, and the corporate imperative to turn a profit force us to look further a field for guidance Industrial involvement: The balance between the desire to alleviate loss of life and suffering, and the corporate imperative to turn a profit force us to look further a field for guidance Ethics concerns relevant to biomaterials: Table 3 Ethics concerns relevant to biomaterials: Table 3

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39. Biomaterials39 TABLE 3 Ethical Concerns Relevant to Biomaterials Science Is the use of animals justified? Specifically, is the experiment well designed and important so that the data obtained will justify the suffering and sacrifice of the life of a living creature? Is the use of animals justified? Specifically, is the experiment well designed and important so that the data obtained will justify the suffering and sacrifice of the life of a living creature? IACUC: Institutional Animal Care and Use Committee IACUC: Institutional Animal Care and Use Committee

40. Biomaterials40 TABLE 3 Ethical Concerns Relevant to Biomaterials Science How should research using humans be conducted to minimize risk to the patient and offer a reasonable risk-to-benefit ratio? How can we best ensure informed consent? How should research using humans be conducted to minimize risk to the patient and offer a reasonable risk-to-benefit ratio? How can we best ensure informed consent? IRB: institutional review board IRB: institutional review board

41. Biomaterials41 TABLE 3 Ethical Concerns Relevant to Biomaterials Science Companies fund much biomaterials research and own proprietary biomaterials. How can the needs of the patient be best balanced with the financial goals of a company? Consider that someone must manufacture devices—these would not be available if a company did not choose to manufacture them. Companies fund much biomaterials research and own proprietary biomaterials. How can the needs of the patient be best balanced with the financial goals of a company? Consider that someone must manufacture devices—these would not be available if a company did not choose to manufacture them.

42. Biomaterials42 TABLE 3 Ethical Concerns Relevant to Biomaterials Science Since researchers often stand to benefit financially from a successful biomedical device and sometimes even have devices named after them, how can investigator bias be minimized in biomaterials research? Since researchers often stand to benefit financially from a successful biomedical device and sometimes even have devices named after them, how can investigator bias be minimized in biomaterials research?

43. Biomaterials43 TABLE 3 Ethical Concerns Relevant to Biomaterials Science For life-sustaining devices, what is the trade-off between sustaining life and the quality of life with the device for the patient? Should the patient be permitted to “pull the plug” if the quality of life is not satisfactory? For life-sustaining devices, what is the trade-off between sustaining life and the quality of life with the device for the patient? Should the patient be permitted to “pull the plug” if the quality of life is not satisfactory?

44. Biomaterials44 TABLE 3 Ethical Concerns Relevant to Biomaterials Science With so many unanswered questions about the basic science of biomaterials, do government regulatory agencies have sufficient information to define adequate tests for materials and devices and to properly regulate biomaterials? With so many unanswered questions about the basic science of biomaterials, do government regulatory agencies have sufficient information to define adequate tests for materials and devices and to properly regulate biomaterials?

45. Biomaterials45 TABLE 3 Ethical Concerns Relevant to Biomaterials Science Should the government or other “third- party payors” of medical costs pay for the health care of patients receiving devices that have not yet been formally approved for general use by the FDA and other regulatory bodies? Should the government or other “third- party payors” of medical costs pay for the health care of patients receiving devices that have not yet been formally approved for general use by the FDA and other regulatory bodies?

46. Biomaterials46 TABLE 3 Ethical Concerns Relevant to Biomaterials Science Should the CEO of a successful multimillion dollar company that is the sole manufacturer a polymer material (that is a minor but crucial component of the sewing ring of nearly all heart valves) yield to the stockholders’ demands that he/she terminate the sale of this material because of litigation 訴訟 concerning one model of heart valve with a large cohort of failures? The company sells 32 pounds of this material annually, yielding revenue of approximately $40,000? Should the CEO of a successful multimillion dollar company that is the sole manufacturer a polymer material (that is a minor but crucial component of the sewing ring of nearly all heart valves) yield to the stockholders’ demands that he/she terminate the sale of this material because of litigation 訴訟 concerning one model of heart valve with a large cohort of failures? The company sells 32 pounds of this material annually, yielding revenue of approximately $40,000?

47. Biomaterials47 TABLE 3 Ethical Concerns Relevant to Biomaterials Science Should an orthopedic appliance company manufacture two models of hip joint prostheses: Should an orthopedic appliance company manufacture two models of hip joint prostheses: one with an expected “lifetime” of 20 years (for young, active recipients) and one with an expected “lifetime” of 20 years (for young, active recipients) and another that costs one-fourth as much with an expected lifetime of 7 years (for elderly individuals), another that costs one-fourth as much with an expected lifetime of 7 years (for elderly individuals), with the goal of saving resources so that more individuals can receive the appropriate care? with the goal of saving resources so that more individuals can receive the appropriate care?

48. Biomaterials48 Subjects Integral to Biomaterials Science Regulation Regulation: To prevent inadequately tested devices and materials from coming on the market, and to screen out individuals clearly unqualified to produce biomaterial, a complex national regulatory system has been erected by the United States government through the Food and Drug Administration (FDA). Regulation: To prevent inadequately tested devices and materials from coming on the market, and to screen out individuals clearly unqualified to produce biomaterial, a complex national regulatory system has been erected by the United States government through the Food and Drug Administration (FDA). Through the International Standards Organization (ISO), international regulatory standards have been developed for the world community. Through the International Standards Organization (ISO), international regulatory standards have been developed for the world community. CE Mark: CE marking is a key indicator of a product's compliance with EU legislation and enables the free movement of products within the European market. By affixing the CE marking on a product, a manufacturer is declaring, at their sole responsibility, conformity with all of the legal requirements to achieve CE marking and therefore ensuring validity for that product to be sold throughout the European Economic Area CE Mark: CE marking is a key indicator of a product's compliance with EU legislation and enables the free movement of products within the European market. By affixing the CE marking on a product, a manufacturer is declaring, at their sole responsibility, conformity with all of the legal requirements to achieve CE marking and therefore ensuring validity for that product to be sold throughout the European Economic AreaEU legislation European marketEU legislation European market

49. Biomaterials49 Subjects Integral to Biomaterials Science : Regulation The cost to meet the standards and to demonstrate compliance with material, biological, and clinical are enormous. The cost to meet the standards and to demonstrate compliance with material, biological, and clinical are enormous. Introducing a new biomedical device to the market require a regulatory investment of many millions dollars. Introducing a new biomedical device to the market require a regulatory investment of many millions dollars. Are the regulations and standards truly addressing the safety issue? Are the regulations and standards truly addressing the safety issue? Is the cost of regulations inflating the cost of health care and preventing improved devices from those who need them? Is the cost of regulations inflating the cost of health care and preventing improved devices from those who need them? Under this regulation topic, we see the interaction of all the players in the biomaterials community: government, industry, ethics and basic science. Under this regulation topic, we see the interaction of all the players in the biomaterials community: government, industry, ethics and basic science.

50. Biomaterials50 Construction materials The different conditions of use have led to an equally varied range of accepted biomaterials The different conditions of use have led to an equally varied range of accepted biomaterials Tissue replacement with synthetics: selecting the material that has physical properties most similar to those natural tissue. Tissue replacement with synthetics: selecting the material that has physical properties most similar to those natural tissue. Table 1.2: surgical applications of Table 1.2: surgical applications of Table 1.2 Table 1.2 metal, alloys, ceramics, polymers, and composite. metal, alloys, ceramics, polymers, and composite. Table 1.3: mechanical properties of biological materials and biomaterials. Table 1.3: mechanical properties of biological materials and biomaterials. Table 1.3 Table 1.3 Ultimate strength and modulus, Ultimate strength and modulus,

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53. Biomaterials53 Construction materials Rigid metal alloys, ceramics, fiber reinforced composites and high molecular weight polymers: replace bone and dentin. Rigid metal alloys, ceramics, fiber reinforced composites and high molecular weight polymers: replace bone and dentin. Soft and pliable elastomers: soft tissue reconstruction Soft and pliable elastomers: soft tissue reconstruction Electrically conducting metal: electrode Electrically conducting metal: electrode Optical transparent plastics: intraocular prostheses. Optical transparent plastics: intraocular prostheses.

54. Biomaterials54 Construction materials- Metals Metals: 3 main alloy, Metals: 3 main alloy, titanium-aluminum, titanium-aluminum, stainless steel stainless steel cobalt-chromium; cobalt-chromium; high load bearing application in skeletal system. high load bearing application in skeletal system. Conducting metals: platinum and platinum- iridium; electrical stimulation Conducting metals: platinum and platinum- iridium; electrical stimulation Nitinol (nickel and titanium): orthodontics, stent Nitinol (nickel and titanium): orthodontics, stent

55. Biomaterials55 Construction materials- Ceramics Alumina (Al 2 O 3 ): stable and inert ceramic material; orthopedic joint replacements. Alumina (Al 2 O 3 ): stable and inert ceramic material; orthopedic joint replacements. Bioglass: improve surface properties of alumina and metal alloy Bioglass: improve surface properties of alumina and metal alloy Degradable ceramics: calcium phosphates application in hard tissue regeneration. Degradable ceramics: calcium phosphates application in hard tissue regeneration. Inert carbon: improve blood compatibility in cardiovascular application. Inert carbon: improve blood compatibility in cardiovascular application.

56. Biomaterials56 Construction materials- Polymers Polymers: physical properties resemble of soft tissue: skin, tendons, cartilage, vessel walls, lens, breast and bladder. Polymers: physical properties resemble of soft tissue: skin, tendons, cartilage, vessel walls, lens, breast and bladder. A number of synthetic polymer used as biomaterials: A number of synthetic polymer used as biomaterials: polyolefins (as polyethylene 多乙烯,(CH 2 -CH 2 ) n ), polyolefins (as polyethylene 多乙烯,(CH 2 -CH 2 ) n ), polyamide, polyamide, polyester, polyester, polyurethanes, polyurethanes, polyacrylate, polyacrylate, polysulfones, polysulfones, polyethers and polyethers and silicone rubber. silicone rubber. Also used as sutures, tissue adhesives, shunts, catheters, and space fillers. Also used as sutures, tissue adhesives, shunts, catheters, and space fillers.

57. Biomaterials57 Construction materials- polymers Biodegradable polymers (natural and synthetic polymers, polyamides): biodegradable suture or bone plates which provide temporary scaffolding or support Biodegradable polymers (natural and synthetic polymers, polyamides): biodegradable suture or bone plates which provide temporary scaffolding or support Various drug delivery system: biodegradable polymers Various drug delivery system: biodegradable polymers Reconstituted collagen polymers: arterial wall, heart valves and skin Reconstituted collagen polymers: arterial wall, heart valves and skin Membrane from natural and synthetic polymers: extracorporeal device: dialysers and oxygenators Membrane from natural and synthetic polymers: extracorporeal device: dialysers and oxygenators Smart polymers: stimulus sensitive polymers Smart polymers: stimulus sensitive polymers Tissue Engineering Tissue Engineering

58. Biomaterials58 Construction materials- Composites Composite materials: consists two or more types of phase usually include stiff fibers embedded in a ductile matrix yielding materials with properties are between those phases. Composite materials: consists two or more types of phase usually include stiff fibers embedded in a ductile matrix yielding materials with properties are between those phases. Carbon fiber embedded in Teflon matrix to obtain a material called Proplast having more desirable properties than either of constituents Carbon fiber embedded in Teflon matrix to obtain a material called Proplast having more desirable properties than either of constituents

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62. Biomaterials62 Construction materials Tissue Engineering: Define: application of the principles of engineering as biology towards a fundamental understanding of the structure-function relationship of tissue and the development of biological substitute to restore, maintain or improve tissue function. Define: application of the principles of engineering as biology towards a fundamental understanding of the structure-function relationship of tissue and the development of biological substitute to restore, maintain or improve tissue function. Scaffold, cell, and mediator. Scaffold, cell, and mediator.

63. Biomaterials63 Impact of biomaterials Early days: few engineering materials used biomaterials. Early days: few engineering materials used biomaterials. Recent years: more than 50 materials Recent years: more than 50 materials Wound and burn dressing: perhaps the most widely used biomaterials Wound and burn dressing: perhaps the most widely used biomaterials Arthritis leading to joint disorder: need correction, total knee and hip replacements are achieved using implants that are composites of metal, polymer and ceramic Arthritis leading to joint disorder: need correction, total knee and hip replacements are achieved using implants that are composites of metal, polymer and ceramic

64. Biomaterials64 Impact of biomaterials Implants: regularly used in ophthalmology, Implants: regularly used in ophthalmology, include lens implants, include lens implants, viscoelastic solutions for eye surgery, viscoelastic solutions for eye surgery, corneal transplants and. corneal transplants and. Facial implants are becoming widely used by surgeons for reconstructive as well as pure cosmetic reasons Facial implants are becoming widely used by surgeons for reconstructive as well as pure cosmetic reasons

65. Biomaterials65 Impact of biomaterials Oral implants: artificial teeth or dentures and dental appliance that support and anchor artificial teeth. Oral implants: artificial teeth or dentures and dental appliance that support and anchor artificial teeth. Vascular grafts: synthetic polymers are routinely used to replace the aorta Vascular grafts: synthetic polymers are routinely used to replace the aorta The replacement of diseased heart valve and bypassing blocked coronary arteries are also achieved on a massive scale. The replacement of diseased heart valve and bypassing blocked coronary arteries are also achieved on a massive scale.

66. Biomaterials66 Impact of biomaterials The other most common implants are sutures, surgical tapes and tissue adhesives, which are indispensable for some surgical procedures The other most common implants are sutures, surgical tapes and tissue adhesives, which are indispensable for some surgical procedures Rupture of anterior cruciate ligament (ACL) repaired with either biological or synthetic replacements. Rupture of anterior cruciate ligament (ACL) repaired with either biological or synthetic replacements.

67. Biomaterials67 Impact of biomaterials The search for new biomaterials has been largely associated with improving life, biocompatibility and finding new applications. The search for new biomaterials has been largely associated with improving life, biocompatibility and finding new applications. In the near future, many synthetic biomaterials will engage in true tissue engineering that grow a number of tissue types as well, as opposed to implanting bioinert materials that only mimic the shape of living tissue and provide mechanical support. In the near future, many synthetic biomaterials will engage in true tissue engineering that grow a number of tissue types as well, as opposed to implanting bioinert materials that only mimic the shape of living tissue and provide mechanical support.

68. Biomaterials68 Impact of biomaterials Drug delivery The use of biomaterials to deliver biological active agents is an attractive concept because local administration of certain therapeutic agents is often the most effective method of treatment. The use of biomaterials to deliver biological active agents is an attractive concept because local administration of certain therapeutic agents is often the most effective method of treatment. Local administration of antibiotics from bone cements for prevention of deep wound infections Local administration of antibiotics from bone cements for prevention of deep wound infections The development of controllable, long-term, effective release systems for the delivery of growth hormone may improve wound healing and tissue repair. The development of controllable, long-term, effective release systems for the delivery of growth hormone may improve wound healing and tissue repair.

69. Biomaterials69 Strength of biological tissues Yamada (1970) has presented strength data on bones, tendons, cartilage, ligaments, skin, muscles and some other tissues of man and other animals of different ages and sexes under static tension, compression, torsion and bending, dynamic impact loads or fatigue oscillations. Yamada (1970) has presented strength data on bones, tendons, cartilage, ligaments, skin, muscles and some other tissues of man and other animals of different ages and sexes under static tension, compression, torsion and bending, dynamic impact loads or fatigue oscillations. Materials Testing System (MTS) is used for mechanical testing. Materials Testing System (MTS) is used for mechanical testing.

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73. Biomaterials73 Strength of biological tissues Failure characteristics of living tissues and organs is especially complex, because there are many ways material can “fail” in biological sense. Failure characteristics of living tissues and organs is especially complex, because there are many ways material can “fail” in biological sense. Besides yielding, plastic deformation, creep, rupture, fatigue, corrosion, wear and impact fracture, one has to consider other kinds of failures. Besides yielding, plastic deformation, creep, rupture, fatigue, corrosion, wear and impact fracture, one has to consider other kinds of failures. To study strength of biological materials, one has to correlate clinical observations and pathological lesions with stress and strain in the tissue. To study strength of biological materials, one has to correlate clinical observations and pathological lesions with stress and strain in the tissue.

74. Biomaterials74 Performance of implants In order to properly assess the performance of biomaterial, it is necessary to carefully review the physiology, anatomy, biochemistry and biomechanics of normal tissues as well as pathophysiological changes In order to properly assess the performance of biomaterial, it is necessary to carefully review the physiology, anatomy, biochemistry and biomechanics of normal tissues as well as pathophysiological changes Most implant require surgical procedure, it is necessary to know the repair and regeneration response. Most implant require surgical procedure, it is necessary to know the repair and regeneration response. Fig 1.1 gives interdependence of engineering factors affecting the success of joint replacement. Fig 1.1 gives interdependence of engineering factors affecting the success of joint replacement. Fig 1.2 illustrates the probability of failure. Fig 1.2 illustrates the probability of failure.

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77. Biomaterials77 Tissue response to implants Biocompatible: materials display good or harmonious behavior in contact with tissue and body fluid. Biocompatible: materials display good or harmonious behavior in contact with tissue and body fluid. The response of the body to implants varies widely according to the host, site and species, the degree of trauma imposed during implantation, and nature of implant material. The response of the body to implants varies widely according to the host, site and species, the degree of trauma imposed during implantation, and nature of implant material.

78. Biomaterials78 Tissue response to implants Generally, the body’s reaction to foreign materials is to reject them. Generally, the body’s reaction to foreign materials is to reject them. The foreign materials may be extruded or walled off, if can not be removed from the body. The foreign materials may be extruded or walled off, if can not be removed from the body. If the materials is particle or fluid then it is ingested by the giant cell (macrophages) and removed. If the materials is particle or fluid then it is ingested by the giant cell (macrophages) and removed. These process are related to wound healing. These process are related to wound healing. Next figure shows the temporal inflammatory Next figure shows the temporal inflammatory

79. Biomaterials79 4.2.1 Overview: Inflammation, wound healing, and the foreign-body response

80. Biomaterials80 Tissue response to implants However, if the implant is inert to the tissue, then the macrophage may not be present near the present; only a thin layer of protein encapsulates the implant. However, if the implant is inert to the tissue, then the macrophage may not be present near the present; only a thin layer of protein encapsulates the implant. Porous implant are fixed by ingrowth of surrounding tissues Porous implant are fixed by ingrowth of surrounding tissues Some implant may cause necrosis of tissue by chemical, mechanical and thermal trauma. Some implant may cause necrosis of tissue by chemical, mechanical and thermal trauma. A brief summary of tissue response to implant. A brief summary of tissue response to implant.

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82. Biomaterials82 Interfacial phenomena Four types of biomaterials in terms of interfacial response of tissue 1. Inert, smooth surface 2. Nearly inert, microporous surface 3. Controlled reactive surface 4. Resorbable

83. Biomaterials83 Interfacial phenomena Major biomaterials in use are type 1 (Inert, smooth surface) : Major biomaterials in use are type 1 (Inert, smooth surface) : suitable combination of physical properties with a minimal toxic response in the host. suitable combination of physical properties with a minimal toxic response in the host. However, the physical response yield thin fibrous capsule (0.1 – 10 μm) surrounding the implant. However, the physical response yield thin fibrous capsule (0.1 – 10 μm) surrounding the implant. Lack of adherence of capsule to implant results in motion of the tissue implant interface. Lack of adherence of capsule to implant results in motion of the tissue implant interface.

84. Biomaterials84 Interfacial phenomena Type 2 and 3 (2. Nearly inert, microporous surface; 3.Controlled reactive surface) designed to improve the stability of interface. When the rate of surface reactions are correctly controlled, the repairing tissues are incorporated structurally within the reactive layers in the implant surface. Type 2 and 3 (2. Nearly inert, microporous surface; 3.Controlled reactive surface) designed to improve the stability of interface. When the rate of surface reactions are correctly controlled, the repairing tissues are incorporated structurally within the reactive layers in the implant surface. Type 4 biomaterial (Resorbable) is designed to be ultimately replaced by regenerating tissue eliminating the original interface altogether. Type 4 biomaterial (Resorbable) is designed to be ultimately replaced by regenerating tissue eliminating the original interface altogether.

85. Biomaterials85 Safety and Efficiency Testing Standard for biomedical materials and devices: Standard for biomedical materials and devices: ISO (International Standards Organization). ISO (International Standards Organization). ASTM (American Society for Testing Materials). ASTM (American Society for Testing Materials). Food and Drug Administration (FDA) monitors the standard of drugs, delivery system, implants and other medical devices. Food and Drug Administration (FDA) monitors the standard of drugs, delivery system, implants and other medical devices.

86. Biomaterials86 Safety and Efficiency Testing The requirement for biomaterials include functional feasibility, biostability, biocompatibility, sterilizability. The requirement for biomaterials include functional feasibility, biostability, biocompatibility, sterilizability. Normally, biological and animal tests are evaluated to demonstrate that a medical device is safe prior to clinical trails Normally, biological and animal tests are evaluated to demonstrate that a medical device is safe prior to clinical trails Efficiency and biocompatibility of medical devices are established prior market. Efficiency and biocompatibility of medical devices are established prior market.

87. Biomaterials87 Summary Materials including polymers, metals, ceramics, and composites (nature materials) with appropriate physical properties and biocompatibility are chosen for the fabrication of medical devices Materials including polymers, metals, ceramics, and composites (nature materials) with appropriate physical properties and biocompatibility are chosen for the fabrication of medical devices The design and testing of medical devices is a interdisciplinary effort involving scientists, engineers and physicians. The design and testing of medical devices is a interdisciplinary effort involving scientists, engineers and physicians. The physiology, anatomy, biochemistry and biomechanics of normal tissues are considered for the effective design of medical devices. The physiology, anatomy, biochemistry and biomechanics of normal tissues are considered for the effective design of medical devices.

88. Biomaterials88 Summary The devices are validated for biocompatibility, biofunctionality based on standard procedures in animal models and subsequent detailed clinical trials prior to marketing. The devices are validated for biocompatibility, biofunctionality based on standard procedures in animal models and subsequent detailed clinical trials prior to marketing.

89. Biomaterials89 Subjects Integral to Biomaterials Science Summary: Biomaterials science may be the most interdisciplinary of all the sciences. Summary: Biomaterials science may be the most interdisciplinary of all the sciences. Consequently, biomaterials scientist must master material from many fields of science, technology, engineering, and medicine in order to be competent in this profession. Consequently, biomaterials scientist must master material from many fields of science, technology, engineering, and medicine in order to be competent in this profession.

90. Biomaterials90 To be continued…. Tissue Engineering