P8 037: Introduction to Biomaterials

生醫材料導論

(Taught in English)

葉明龍 Phone: 63429 Email: [email protected]

1

Alternative: P8 017 Chemistry of Biomaterials 生物材料化學

張憲彰

Wed. 5-7

2



Time:

Mon. 6-8 (2:10-5:00 PM) 

Office hours:

Wednesday, Thursday 10AM -12PM (Biomedical Engineering 5751A) 

Grade:

 Homework: 30%  Tests: 50%  Final paper and Presentation: 20% 3/68

Textbooks

:

Intend for Non-Materials background 

Fundamentals of Materials Science and Engineering (Chap 2-9)

By: William D. Callister Jr.



Biomaterials Science: An Introduction to Materials in Medicine (Chap 1, 2)

By: Ruddy D. Ratner; Allan Hoffman; Frederick Schoen and Jack Lemons 4/68

 

Introductory book:

生物醫學材料 王盈錦

References:

1. Biomaterials by Sujata Bhat 2. Biomaterials: An Introduction by Joon Bu Park 5/68

Students Self Introduction

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3.

4.

5.

1.

Fill your name, email, phone, Institute, Grade (Year) and Advisor Name, Institute, Grade (Year) Advisor Main focus of your lab Possible research direction 6/68

Curriculum:

Week Content 1. Opening statement: Introduction (Biomaterials Page 1-9) 2.

I. Materials Science and Engineering

Chap 2 Atomic Structure and Interatomic Bonding Chap 3. Structures of Metals and Ceramics 3. Chap 4. Polymer Structure Chap 5 Imperfections in Solids 4. Chap 6. Diffusion Chap 7. Mechanical Properties 5. Chap 8. Deformation and Strengthening Mechanisms Chap 9. Failure 6.

Test I

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Curriculum:

7.

II. Biomaterials

1.4 Surface properties and surface characterization 1.5 Role of water in biomaterials 8. 2.2 Polymers 9. 2.3 Silicone Biomaterials 2.4 Medical fibers and biotextiles 10. 2.5 Hydorgels 2.6 Smart Polymers 11. 2.7 Bioresorbable and Bioerodible Materials 2.8 Natural Materials 12. 2.9 Metals 8/68

Curriculum:

13.

14.

15. 16. 17. 18. 2.10 Ceramics, Glasses, and Glass-Ceramics 2.11 Pyrolytic Carbon 2.12 Composite 2.13 Nonfouling surfaces 2.14 Physicochemical Surface modification 2.15 Textured and Porous Materials 2.16 Surface-Immobilized Biomolecules

Final presentation Test II

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Biomaterials: Definition

 (1987, Williams) A biomaterial is a nonviable material used in a medical device , intended to interact with biological system.

  (Bhat) 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.

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Definition:

 (Merriam-Webster) Materials used for or suitable for used in prostheses that comes in direct contact with living tissues.  Biocompatibility: ability of a material to perform with an appropriate host response in a specific application 11/68

Introduction

  Biomaterials used in these devices:  ophthalmology,  cardiology,  neuromuscular surgery,  orthopedics and  dentistry . All biomaterials in common;  they must have intimate contact with patient’s tissue or body fluid,  providing a real physical interface .

 The search for new, more reliable devices require a disciplined scientific approach to the subject.

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Introduction: Biocompatibility

 Good biocompatibility is achieved when the material exists within a living body without adversely or significantly affecting it or being affected by it .  The material should have

adequate

strength , chemical and physical mechanical properties.  Thus biomaterials must be compatible with body tissues mechanically, chemically as well as pharmacologically . 13/68

Introduction

 1.

2.

3.

To research these materials the investigator need to have arrange of techniques for materials production , measurement of strength and surface properties and

in vitro

and

in vivo

techniques for biocompatibility evaluation.

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Introduction

 The functions of implants fall into one the following categories:  Load bearing or transmission  fixation artificial joint, fracture  The control of fluid flow in order to stimulate normal physiological function or situation  vascular graft, stent  Passive space filling functional reasons  either for cosmetic bone filling, skin reasons or  Generation of electric stimuli and sound .

 electrode and transmission of light 15/68

Biomaterials: General perspective

  Biomaterials 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 fabricated, sterilized form) (final 16/68

Biomaterials science

  The physical and biological study of materials interaction with the biological environment . and their Traditionally investigation:  biomaterials synthesis, optimization, characterization, testing   the biology of host-material interactions. Most biomaterials introduce a non-specific, stereotyped biological reaction.

 Current effort:   toward the development of engineered surfaces that could elicit rapid and highly precise reactions with cells and proteins , tailored to a specific application.

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Biocompatibility

 Indeed, a complementary definition essential for understanding the goal (i.e., specific end applications ) of biomaterials science is that of “biocompatibility”.

 "Biocompatibility” is the ability of a material to perform with an appropriate host response in a specific application (Williams, 1987).

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Biocompatibility

 Examples of "appropriate host responses" include  the resistance to blood clotting,  resistance to bacterial colonization, and  normal, uncomplicated healing. 19/68

Biocompatibility

 This general concept of biocompatibility has been

extended

recently in the broad approach called "tissue engineering"  careful selection of

cells, materials, and metabolic and biomechanical conditions

regenerate functional tissues.

to 20/68

Classic Examples of Biomaterials

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Classic Examples: Table 1

(Ratner)

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Classic Examples: Table 1

(Ratner)

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Classic Examples: Table 1

(Ratner)

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Biomaterials and health care market

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 

Classic Examples

Substitute Heart valves

from : Heart valve prostheses are fabricated carbons, metals, elastomers, fabrics enhance durability. and natural (e.g. pig) valves and other tissues chemically pretreated to reduce their immunologic reactivity and Problem: degeneration of tissue , mechanical failure, postoperative infection, and induction of blood clot. 28/68

   

Classic Examples

Artificial Hip Joint

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

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Classic Examples

 

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). 30/68

Classic Examples



Intraocular Lenses :

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. 31/68

Characteristics of Biomaterials Science

 Multidisciplinary  Many diverse materials  Development of biomaterials devices  Magnitude of the field  Success and failure 32/68

Characteristics of Biomaterials Science: Multidisciplinary



More than any other field of contemporary technology, biomaterials science brings together researchers from diverse backgrounds who must communicate clearly.



Figure 6 lists some of the disciplines that are encountered in the progression from identifying the need for a biomaterial device to its manufacture, sale, and or implantation .

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Many Diverse Materials:

 The biomaterials scientist will have an appreciation of materials science .  This may range from  an impressive command of the theory and  practice of the field demonstrated by the professional materials scientist to  a general understanding of the properties of materials that might be demonstrated by the physician or biologist investigator involved in biomaterials-related research .

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Many Diverse Materials:

 A wide range of materials is routinely used and no one researcher will be comfortable synthesizing and designing with all these materials . 36/68

Many Diverse Materials:

 Hard tissue replacement biomaterials: metals, ceramics, used in orthopedic and dental 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.

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Development of biomaterials devices: Fig 6.

      It provides a perspective on how different disciplines work together , starting from the identification of a need for a biomaterial through development, manufacture, implantation, and removal from the patient.

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Characteristics of Biomaterials Science

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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. 40/68

Success and Failure

 Most biomaterials and medical devices perform satisfactorily , improving the quality of life recipient or saving lives. for the  However, no manmade construct is perfect.  All manufactured devices have a failure rate.  Also, all humans are different with differing genetics, gender, body chemistries, living environment, and degrees of physical activity .  Furthermore, physicians implant or use these devices with varying degrees of skill . 41/68

Success and Failure

  The other side to the medical device success story is that there are problems, compromises, and complications devices. that occur with medical Central issues for the biomaterials scientist, manufacturer, patient, physician, and attorney are, (1) what represents good design, (2) who should be responsible when devices perform " with an inappropriate host response ," and (3) what are the cost/risk or cost/benefit ratios implant or therapy?

for the 42/68

Success and Failure

    Some examples may clarify these issues. Clearly, heart valve disease problem. Patients with diseased aortic heart valves have a is a serious medical 50 % chance of dying within 3 years. Surgical replacement of the diseased valve leads to an expected survival of 10 years in 70 % of the cases. However, of these patients whose longevity and quality of life have clearly been enhanced, approximately 60 % will suffer a serious valve related complication within 10 years after the operation. 43/68

Subjects Integral to Biomaterials Science

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        

Subjects Integral to Biomaterials Science

Toxicology Biocompatibility Functional tissue structure and pathobiology Healing Dependence on specific anatomical site Mechanical and Performance requirements : Industrial involvement Ethics

(Table 3)

Regulation

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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 do so. unless it is specifically designed to 46/68

    

Biocompatibility:

The understanding and measurement of biocompatibility is unique to biomaterials science. Unfortunately, we do not definitions or have precise accurate measurements of biocompatibility. 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. In fact, biocompatibility may have to be uniquely defined for each application .

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  1.

2.

3.

Functional tissue structure and pathobiology

Biomaterials incorporated into medical devices are implanted into tissues and organs. Critical considerations to workers in the field.

The key principles governing the structure normal and abnormal cells, tissues, and organs, of the techniques by which the structure and function of normal and abnormal tissue are studied, and the fundamental mechanisms processes of disease 48/68

Healing

    Injury to tissue will stimulate the well define inflammatory reaction sequence that lead to healing. When a foreign body sequence is referred to as “foreign body reaction”. is involved, the reaction 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. 49/68



Dependence on specific anatomical site

: Each site challenges the biomedical device designer with special requirements for geometry, size, mechanical properties, and bioreaction .

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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: mechanical performance, mechanical durability, and physical properties (functional). 51/68

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 afield (out of the way) for guidance.

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Ethics (1)

 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?

 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?

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Ethics (2)

   Companies fund much biomaterials research and own proprietary biomaterials. How can the needs of the patient the financial goals of a company? be best balanced with Consider that someone must manufacture devices - these would not be available if a company didn’t choose to manufacture them.  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?

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Ethics (3)

 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? 56/68

Ethics (4)

 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?

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Ethics (5)

 Should the government or other "third party payers" 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? 58/68

Ethics (6)

 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 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?

Cohort: a group of individuals having a statistical factor (as age or class membership) in common in a demographic study 59/68

Ethics (7)

 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 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?

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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. 61/68

Regulation

 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 .  Are the regulations and standards truly addressing the safety issue

?

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Regulation

 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 . 63/68

Summary

:

  A broad overview of the biomaterials field . It provides a vantage point from which the reader can gain a perspective to see how the sub-themes fit into the larger whole .

Biomaterials science may be the most multidisciplinary all the sciences. 64/68

Summary

:

 Consequently, biomaterials scientists must master certain key material from many fields of science, technology, engineering, and medicine in order to be competent and conversant in this profession.  The reward for mastering this volume of material is immersion in an intellectually stimulating endeavor that advances a new basic science of biointeraction and contributes to reducing human suffering.

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Summary:

 Basic definition of biomaterials  Example of biomaterials application  Characteristics of biomaterials Science  Multidisciplinary  Many diverse materials  Development of biomaterials Devices  Magnitude of the field  Success and failure 66/68

Summary:



Subjects Integral to Biomaterials Science



Toxicology

: 

Biocompatibility



Functional tissue structure and pathobiology



Healing:



Dependence on specific anatomical site



Mechanical and Performance requirements:



Industrial involvement

: 

Ethics

(Table 3) 

Regulation

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I.

II.

III.

Home work I:

Due: Next week (9/20/2010) Find an abstract from the least issue of “Biomaterials” and write your opinion about this paper. (100-300 words) (30%) End Note: Following question I, copy the text of Introduction or Discussion with 10-20 references from that paper and use End Note to cite these reference. Build a End Note file for these reference. (45%) What is your opinion about the ethical concerns related to biomaterials science? Please answer “one” of the issues from Table 3 (in page 8). Choose anyone from that table. (25 %) (100-300 words) 68/68

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 Some helpful dictionary sites:    http://www.m-w.org/ http://dictionary.reference.com/ http://dict.vghtpe.gov.tw/search.php

   http://tw.dictionary.yahoo.com/ http://www.hk-doctor.com/html/dict.php

????

http://www.google.com.tw/ 70/68

To be continued…….

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Success and Failure

    Another example involves LVADs. A clinical trial called Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) led to the following important statistics (Roseetal., 2001). Patients with an implanted Heartmate LVAD (Thoratec Laboratories) had a 52 % chance of surviving for 1 year, compared with a 25 % survival rate for patients who took medication. Survival for 2 years in patients with the Heartmate was 23 % versus 8 % in the medication group.

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Success and Failure

 Also, the LVAD enhanced the quality of life for the patients 一 they felt better, were less depressed, and were mobile.  Importantly, patients participating in the REMATCH trial were not eligible for a heart transplant.  In the cases of the heart valve and the LVAD, long 一 term clinical complications associated with imperfect performance of biomaterials do not preclude clinical success overall.

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Success and Failure

 These five characteristics of biomaterials science : (1)multidisciplinary, (2)multimaterial, (3)need-driven, (4)substantial market, and (5)risk-benefit, flavor all aspects the field.  In addition, there are certain subjects that are particularly prominent in our field and help delineate biomaterials science as a unique endeavor · Let us review a few of these.

to describe, portray, or set forth with accuracy or in detail 74/68