Biocompatibility: Chapter 9 - Biocompatibility And Handouts

Front 1

Consideration of biomaterials and devices is not complete until what happens?

Back 1

Until their biocompatibility with the body fluids, tissues, and organs of the body has been tested.

Front 2

What are 4 methods that evaluate immune response?

Back 2

1. Functional assays
2. Phenotype identification
3. Soluble mediators
4. Clinical symptoms

Front 3

Initial evaluation tests test for what 8 things?

Back 3

1. Cytotoxicity
2. Sensitization
3. Irritation
4. Systemic toxicity
5. Subacute Toxicity
6. Genotoxicity
7. Implantation
8. Hemocompatibility

Front 4

Supplementary evaluation tests test for what 4 things?

Back 4

1. Chronic Toxicity
2. Carcinogenicity
3. Reproductive/Developmental issues
4. Biodegradation

Front 5

What are 7 Soluble Mediators in the evaluation of immune response?

Back 5

1. Antibodies
2. Complement
3. Immune Complexes
4. Cytokine Patterns
5. Cytokines
6. Chemokines
7. Bioactive Amines

Front 6

What are the 5 Clinical Symptoms of Immune Response?

Back 6

1. Allergy
2. Skin rash
3. Urticaria
4. Edema
5. Lymphadenophathy

Front 7

What is Lymphadenophathy?

Back 7

Swelling of the lymph nodes.

Front 8

What 2 things does Phenotyping test for?

Back 8

1. Cell surface markers
2. MHC Markers

Front 9

What are the 10 types of Functional Assay?

Back 9

1. Skin Testing
2. Lymphocyte Proliferation
3. Plaque-Forming cells
4. Local Lymph Node Assay
5. Mixed Lymphocyte Reaction
6. Tumor Cytotoxicity
7. Antigen Presentation
8. Phagocytosis
9. Degranulation
10. Resistance to bacteria, viruses, and tumors

Front 10

In order, list the 4 steps to the development of biomaterials and devices.

Back 10

Biomaterials in combination with devices must undergo:
In vitro testing of prototypes
Animal Testing
Clinical Trials

Front 11

TRUE OR FALSE: The FDA reviews both materials and devices.

Back 11

FALSE. The FDA only reviews devices.

Front 12

How does a material become a "biomaterial?"

Back 12

A person attempts to use the material in the body.

Front 13

What are Biomaterials?

Back 13

Substances other than foods or drugs contained in therapeutic or diagnostic systems.

Front 14

In the past, biomaterials were developed based on what?

Back 14

Upon a trial-and-error optimization approach

Front 15

What is the old definition of Biocompatible?

Back 15

A biomaterial which is:
Non Toxic
Non Pyrogenic
Non Allergenic
Non Thrombogenic

Front 16

What is the present definition of Biocompatible?

Back 16

Proactive biomaterials which when implanted elicit specific, precice, select, rapid, and timely responses from surrounding proteins, cells, and tissues (interfacial interactions).

Front 17

Define Biocompatibility, presently.

Back 17

A biomaterial which promotes biological processes that enhance the intended aim of the prosthesis as well as being non-mutagenic, non-oncogenic, non-tetatogenic, and not elicit foreign body reactions.

Front 18

What four things must the biocompatible material do?

Back 18

1. Non mutagenic - doesn't cause mutations in DNA
2. Non-oncogenic - doesn't cause tumors
3. Non tetarogenic - doesn't cause flipper babies
4. No foreign body reactions

Front 19

What are Bioactive Materials?

Back 19

Materials which elicit integration in the body!

Front 20

What are Inert Materials?

Back 20

Materials which prevent undesired interactions with surrounding cells and tissues.

Front 21

What is the difference between Bioactive and Inert materials?

Back 21

Bioactive materials elicit integration while inert materials prevent undesired interactions.

Front 22

TRUE OR FALSE: Implantation of materials and devices into the bodies of either humans or animals requires surgical interventions, and thus, trauma.

Back 22

TRUE!

Front 23

What are the 4 highlights to the physiological wound healing process?

Back 23

1. Blood coagulation/platelet activation
2. Inflammation/white blood cell activation
3. Tissue Regeneration
4. A complex cascade of events involving numerous cell types and GFs that are released temporally during the stages of wound healing

Front 24

The interactions between implant materials and the body involve what 3 things?

Back 24

1. Biological events
2. Biophysical events
3. Biochemical events

Front 25

What is the Ultimate Clinical Goal?

Back 25

To induce a successful wound healing process following implantation of prosthetic devices, that results in normal regeneration and functional tissue formation.

Front 26

What is the Ultimate Biocompatible Biomaterial Goal?

Back 26

Engineer (design and formulate) biomaterials that elicit appropriate host responses in specific implant applications.

Front 27

What are 4 biocompatibility issues and consequences that must be maintained?

Back 27

1. Safety to patients
2. Safety to health-care providers
3. Regulatory compliance requirements
4. Legal liability

Front 28

Who conducts biocompatibility studies?

Back 28

Laboratories in universities,
R&D divisions in industry,
commercial companies

Front 29

What are the prerequisites that must be met successfully before evaluation of their biocompatibility?

Back 29

In vitro characterization of materials and of the functional performance must done!

Front 30

What should happen to materials and devices that do NOT pass the prerequisite tests?

Back 30

They should NOT be evaluated for their biocompatibility!

Front 31

Successful synthesis of biomaterials and design of biomedical devices is not complete without what?

Back 31

The evaluation of their biocomatibility AND performance under conditions that simulate those of end-use applications milieu, and time requirements.

Front 32

Determination of the biocompatibility of materials and implantable devices improves what? What does it not do?

Back 32

Our understanding of biological responses but does not ensure that optimal performance will be achieved.

Front 33

Generally, the determination of the biocompatibility of materials and implantable devices involves what?

Back 33

Complex processes as well as in vitro tests, in vivo tests, local and systemic responses.

Front 34

What are 4 Hemocompatibility tests?

Back 34

1. Static tests
2. Tests under flow conditions
3. Acute tests
4. Chronic tests

Front 35

In order to do in vitro cellular models, what kind of cells must be chosen?

Back 35

Mammalian cells that are REPRESENTATIVE of the tissue which will either come into contact with or surround the implant.

Front 36

What are the 4 basic considerations of In Vitro Cellular Models?

Back 36

1. Choosing representative cells
2. Studying cell functions pertinent to application
3. Comparing functions of cells to relevant tissue
4. If pertinent, examining the interaction and function of infecting microorganisms.

Front 37

What are 4 advantages of IN VITRO testing?

Back 37

1. Cost effective
2. Small to reasonable capital investment in facilities and equipment
3. Fast processing of large numbers of candidate materials
4. Studying functions and mechanisms of ONE cell line at a time

Front 38

What is the major limitation of IN VITRO testing?

Back 38

They provide limited view of complex, multifaceted, interactive, and dynamic events that direct, mediate, and control tissue-material interactions.

Front 39

Cellular in vitro systems are now established models for what purpose?

Back 39

Effective SCREENING materials for biocompatibility purposes

Front 40

Laboratory animals in research and testing should be what 2 things?

Back 40

1. Used ONLY AFTER successful completion of prerequisite and in vitro tests
2. Treated with humane care

Front 41

Animal experiments should do what 3 things?

Back 41

1. Not expose animals to unnecessary pain and suffering
2. Avoid use of a large number of test animals and duplication of studies
3. Abide by local, state, and federal laws and regs.

Front 42

What does the US Animal Welfare Act address?

Back 42

The care and use of lab animals by establishing a system for monitoring/controlling animal research.

Front 43

Compliance to regulations is required by federal funding agencies and is scrutinized by who?

Back 43

Review committees in the institutions where the research is conducted.

Front 44

Animal research regulations identify and specifiy what 9 things?

Back 44

1. Animal species that can be used
2. Procurement of animals
3. Animal husbandry - care and daily routine
4. Veterinary care
5. Facilities
6. Training and Credentials of Animal-Care personnel
7. Experimental procedures
8. Record keeping
9. Submission of pertinent reports at regular intervals

Front 45

What are the 4 classificatinos of Animal Testing?

Back 45

1. Nonfunctional - see what the material does in the animal
2. Ex-vivo
3. Functional - actually place the device in the body
4. Local and systemic responses

Front 46

Negative results in animal testing and otherwise mean what?

Back 46

They seal the unacceptability of the tested device.

Front 47

Positive results in animal testing mean what?

Back 47

They do not necessarily prove or predict compatibility of materials and devices to humans.

Front 48

Animal experiments are what two things?

Back 48

1. Useful
2. Unavoidable

Front 49

Successful clinical trials are required before what can happen?

Back 49

Before a biomedical device can be available to the general public

Front 50

In addition to scientific standards and criteria, clinical evaluations of BME devices must do what?

Back 50

Comply with legal regulations!

Front 51

What must be made to satisfy the regulatory agencies?

Back 51

A strong case of the benefits and assurance of the absence of unusual risks to recipients

Front 52

What should always be protected?

Back 52

The rights and dignity of the human subjects!

Front 53

Patients must give what before they can participate in clinical trials?

Back 53

Informed consent!

Front 54

What kind of considerations are involved in the selection of patients who will participate in the trial?

Back 54

Ethical considerations!

Front 55

How long must the identity and medical records of participating patients remain confidential?

Back 55

FOREVER

Front 56

What must be kept, be available for inspection, and/or be submitted to regulatory agencies as needed?

Back 56

DETAILED and COMPLETE records of ALL tests

Front 57

All records must include what 4 things?

Back 57

1. Description of the device
2. Protocols of surgical procedures
3. Postoperative care and medical care of recipients
4. Comparisons of results with appropriate controls

Front 58

Clinical trials establish what?

Back 58

The ultimate biocompatibility of biomaterials and devices.

Front 59

What establishes the ultimate biocompatibility of biomaterials and devices?

Back 59

Clinical Trials

Front 60

Successful completion of clinical trials is required in order to do what?

Back 60

To obtain approval from the regultory agencies to market biomedical devices.

Front 61

What are 3 disadvantages of Clinical Studies?

Back 61

1. Ethical considerations can be complicated
2. They're multifaceted and demanding
3. Require large investment of TIME and MONEY even when they don't result in marketable products.

Front 62

In vitro, ex vivo, and/or animal experiments provide valuable information but do not do what?

Back 62

Do not predict performance of devices in humans.

Front 63

All biocompatibility evaluations should be conducted in accordance to what two things?

Back 63

1. Institutional regulations
2. Federal + international laws

Front 64

Examination of implants retrieved for reasons unrelated to the function of the prostheses provide what?

Back 64

Unquestionable and most valuable evidence regarding the safty and efficacy of implant devices.

Front 65

Detailed study of failed implants can be used to do what 3 things?

Back 65

1. Improve design and fabrication of material/devices
2. Establish selection criteria for implants
3. Develop revised protocols + techniques for various stages in the evaluation of implant design, performance, and biocompatibility.

Front 66

What are 2 future directions in biomaterial science?

Back 66

1. Identify specific design parameters critical to the performance of implants
2. Integrate biomaterials design with new insights emerging from cell-matrix interactions, cellular signaling processes, and developmental + systems biology.

Front 67

Federal regulation of medical devices began when?

Back 67

In 1976 as an amendment to the Federal Food, Drug, and Cosmetic Act.

Front 68

What are the 2 pertinent agencies in the US?

Back 68

FDA and Department of Agriculture

Front 69

What are the 5 properties that need to be characterized in vitro on raw materials before biocompatibility can be done?

Back 69

1. Physicochemical
2. Mechanical
3. Electrical
4. Transport
5. Biodegradation

Front 70

How is blood compatibility of materials and devices determined?

Back 70

By using anticoagulated blood and evaluating the formation of blood clots, triggering of coagulation cascade, platelet adhesion, aggregation, activation of complement system, on the surface of material.

Front 71

What two things in hemocompatibility must be determined under flow conditions and for mechanically moving parts in the vascular system?

Back 71

1. Damage to RBC leading to release of hemoglobin under flow conditions
2. Calcification (of leaflets, heart valves)

Front 72

Why are animal models used?

Back 72

To determine the in vivo compatibility of materials and devices.

Front 73

Name 1 agency and 2 professional organizations that compile detailed instructions regarding protocols and methods pertinent to each stage of the biocompatibility evaluation?

Back 73

National Institutes of Health (NIH)

American Society for the Testing of Materials (ASTM)
International Organization for Standardization (ISO)