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MAT300 > Biocompatibility > Flashcards

Biocompatibility Flashcards

1
Q

What is biocompatibility?

A
  • a material with no toxic or injurious effects on a biological systems
  • The ability of a material to co-exist within a tissue without causing deleterious changes
  • The ability of a material to perform with an appropriate host response in a specific application
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2
Q

What is biocompatibility dependent on?

A

application of the material and the specific function you want it to perform

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3
Q

What is the definition of biocompatibility?

A

Biocompatibility refers to the ability of a biomaterial to perform its desired function with respect to a medical therapy, without eliciting any undesirable local or systemic effects in the recipient or beneficiary of that therapy, but generating the most appropriate beneficial cellular or tissue response in that specific situation, and optimising the clinically relevant performance of that therapy

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4
Q

What are first generation biomaterials?

A

1940-1980

  • non-toxic, non-immunogenic, non-carcinogenic, non-irritating
  • aiming for minimal to no inflammatory or other cellular responses
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5
Q

What is the current approach to biomaterial?

A

Changed from trying to do no harm to active and synergistic interactions between material and biology to do good

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6
Q

What are non-invasive applications of biomaterials?

A

Can be as simple as choosing an inert material that is non-toxic
▻ tongue depressor
Slightly more complex e.gplaster
▻ basic absorbent padding or antibacterial?
▻ Choice of adhesive –irritant, absorbed by skin?
Complex –Tissue engineered skin
▻ Burn treatments -MySkin®, Epicel®
▻ Immune response, drug release/growth factors

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7
Q

What are the types of tissue engineered skin?

A

1) epidermal only

2) full thickness

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8
Q

What is ‘epidermal only’ tissue engineered skin?

A

▻ Confluent sheets of autologous keratinocytes –poor integration with wound bed
▻ Carrier membrane with sub-confluent keratinocytes –better cell growth and integration

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9
Q

What is ‘full thickness’ tissue engineered skin?

A

▻Allogeneic/xenogeneic skin substitutes –disease risk, immune response
▻ Requires revascularisation – Scaffold structure, include growth factors (VEGF)

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10
Q

What are the invasive applications of biomaterials?

A

1) All implanted materials will elicit a cellular response
▻ Inflammatory
▻ Wound healing
▻ Foreign body reaction
2) Severity of cellular response will determine its short and long-term success
3) Permanent, temporary or degradable?
4) Blood contacting or not?

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11
Q

What are non-implanted invasive devices?

A 
1)Cardiopulmonary bypass
 ▻ Blood oxygenator 
2) Dialysis 
3) Catheters 
4) Hypodermic needles
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12
Q

What are degradable sutures?

A

Used as early as the ancient Egyptians

Both material and degradation products must be “biocompatible”

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13
Q

What are examples of degradable sutures?

A

1) Catgut sutures (submucosa of sheep intestine) degraded in 90 days by proteolytic enzymes –Banned in EU due to BSE concerns
2) Polyglycolic acid one type now used and can be modified to degrade at different rates
▻ Quick degradation for fast healing tissues e.g. mucous membranes
▻ Slow degradation for slow healing tissues e.g. Fasci

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14
Q

What are stents?

A

Evolved from simple bare metal designs to complex drug eluting designs to combat neointimal hyperplasia

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15
Q

What is the risk associated with drug eluting stents?

A

increased risk of thrombosis

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16
Q

What are stent coatings a trade off between?

A

reducing inflammation and tissue ingrowth and reducing platelet adhesion and aggregation

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17
Q

What are the functional implications on biocompatibility?

A

1) Mechanical environment also needs to be considered
2) PTFE – Bulk material “biocompatible” and chemically inert
3) Once used as acetabular head in metal on polymer hip replacements
4) Wear particles from PTFE cause extreme inflammatory response in the joint
5) More than just the bulk material is important

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18
Q

What are the device materials used for a stent?

A 
1) Pyrolytic Carbon 
▻ blood contacting –minimally thrombogenic 
▻ Brittle –used as coating only 
2) Titanium 
▻ No blood contact -structural support 
▻ Non-toxic 
3) Polyurethane 
▻ No blood contact –suture support 
▻ Tough and flexible 
▻ Allows cell ingrowth
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19
Q

What material properties influence biocompatibility?

A

1) Physical properties
2) Chemical properties
3) Mechancial properties

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20
Q

How do the physical properties of a material influence biocompatibility?

A

Hydrophobicity/hydrophilicity
Surface charge
Surface roughness/porosity

21
Q

How do the chemical properties of a material influence biocompatibility?

A

▻ Material reactivity –corrosion/degradation

▻ Surface functionalisation –Drugs, protective coatings

22
Q

How do the mechanical properties of a material influence biocompatibility?

A

▻ Young’s modulus, ductility, tensile strength, toughness

▻ Coefficient of friction

23
Q

What is protein adsorption affected by (material wise)?

A

▻ Size, charge, amphipathic nature, protein stability

▻ Surface topography, charge, chemistry

24
Q

What can protein adsorption influence?

A

▻ Thrombus formation
▻ Bacterial contamination
▻ Complement activation
▻ Cell attachment

25
Q

How can a material surface be altered to affect biocompatibility?

A

1) Surface coating
2) Surface roughness (polishing, etching, patterning)
3) Material porosity (no. of pores, pore connectivity, pore size, pore size distribution)

26
Q

What are the types of surface coating?

A

1) Thing surface coating (surface oxidation, polymer coating)
2) Biological functionalisation (heparin, collagen, drugs)
3) Chemical functionalisation (amine, methyl, carboxyl, hydroxyl, and carbonyl groups)

27
Q

What are natural materials?

A

eg. proteins, polysaccharides, decellularized ECM
1) Contains motifs recognised by cells (RGD domains)
2) Typically not cytotoxic
3) Inconsistent physical and mechanical properties
4) Immunogenic –DNA, α-Gal epitopes

28
Q

What are synthetic materials?

A

eg. polymers, ceramics, metals
1) May be cytotoxic
2) Can be consistently produced
3) Inflammatory & foreign body response

29
Q

How can material processing affect biocompatibility?

A

Every processing step could affect biocompatibility

1) Photocurable polyHIPE-UV-light absorber (Tinuvin) added in a processing step to stop surface skin formation
2) Tinuvinextremely cytotoxic, can it all be washed out? ▻ Better alternative -retinoic aci

30
Q

What are the pathways in biocompatibility?

A

1) biomaterial and host contact (surgical implantation)
2) initiation of host response (protein adsorption, cell adhesion)
3) progression of host response (inflammation, hyperplasia, thrombosis, calcification)
4) non tolerable effects of tolerable/beneficial effects

31
Q

For tissues that don’t regenerate, what is the body response to a biomaterical?

A

e. g. Heart muscle
1) Fibrous capsule formation
2) Fibrous tissue interspersed with macrophages
- Want to keep fibrosis to a minimum

32
Q

For tissues that do regenerate, what is the body response to a biomaterical?

A

e. g. Bone
1) Ideally no long lasting macrophage accumulation
3) Material integration
4) No fibrous capsule formation

33
Q

What are the types of immune responses?

A

1) inflammatory

2) immunogenic

34
Q

What are the different types of inflammatory responses?

A

1) Acute inflammation ▻ Minutes-days
▻ Neutrophils and monocytes/macrophages
2) Chronic inflammation
▻ Days-months
▻ Lymphocytes, blood vessel proliferation
3) Foreign body response
▻ Macrophages join to form foreign body giant cells

35
Q

What are different types of immunogenic responses?

A

1) Hyperacute rejection
2) Acute immune rejection
3) Chronic immune rejection

36
Q

What is hyperacute rejection?

A

▻ Antibody binding to xenogeneic antigen e.g α-gal epitope

37
Q

What is acute immune rejection?

A

▻ T-cell activation from antibodies binding to antigens on host cell remnants

38
Q

What is chronic immune rejection?

A

▻ Major histocompatibility complex on donor cells activate T-cells

39
Q

How does protein adsorption lead to inflammation?

A

▻ Non-specific binding of unwanted proteins leads to foreign body response
▻ Surface hydrophobicity

40
Q

How do metal ions lead to inflammation?

A

▻ Allergenic potential –Ni, Co, Cr
▻ Cytotoxic –Ni, Co, Pb
▻ Impaired bone remodelling
▻ Reduce with surface coating e.g. oxide layer

41
Q

How do particles lead to inflammation?

A

(Form from wear at joint)
▻ Metal and polymer
▻ Engulfed by macrophages
▻ Smaller particles stimulate cytokine release and bone resorption

42
Q

What is the influence of cells on materials?

A

1) Cells themselves can induce material corrosion
▻ Contribute to aseptic loosening of dental and orthopaedic implants
2) Enzymes released by cells can increase degradation rates
▻ Premature failure of device

43
Q

How do we determine biocompatibility?

A

!) favourable cellular responses in specific cells
2) favourable lack of effect on cells
( Typically can only be determined by a combination of the effects on critical cells and avoidance of effects in others)

44
Q

What are the advantages of using in vitro testing over vivo testing?

A

▻ More controlled
▻ Doesn’t use animals
▻ Easier & cheaper to perform and interpret
▻ Higher throughput

45
Q

What are the advantages of using in vivo testing over in vitro?

A

▻ Mixture of cells
▻ Physiologically controlled environment (pH, temp etc.)
▻ Needed for commercialisation
▻ Animals do not accurately represent humans

46
Q

What is in vitro biocompatibility testing usually testing for?

A

Testing will depend on the application and material type e.g. synthetic or natural
1) Material cytotoxicity -ISO 10993-(5 & 18)
▻ Degradation products and leachables–local or systemic
▻ Direct contact and MEM elution
▻ MTT assay or other metabolic activity assays
2) Haemocompatibility ISO 10993-4
▻ Platelet activation
▻ Haemolysis
▻ Complement activation
3) Genotoxicity-ISO 10993—3
▻ In vitro testing more common than in vivo
▻ Chromosome aberrations
▻ Gene mutation
4) Carcinogenicity ISO 10993-3
▻ Not commonly used –renewed interest since change in EU cosmetics regulation
▻ Cell transformation assays
5) Reproductive/ developmental toxicity
▻ Not commonly used
▻ Embryonic stem cell test
▻ Micromasstest

47
Q

What is in vitro biocompatibility testing usually testing for?

A

Performed after initial in vitro testing
1) Irritation/sensitisation testing ISO 10993-10
▻ Repeated patch test/Guinea pig maximisation test
2) Cytotoxicity
▻ Subcutaneous implant
3) Haemocompatibility
▻ Shunt
4) Genotoxicity/ carcinogenicity/reproductive /developmental
▻ Implant material and assess short and long term effect

48
Q

How are complete rupture of tendons currently treated?

A

suturing the ruptured ends together

autograft

49
Q

What are the advantages and disadvantages of autografts for the treatment of complete rupture of tendons?

A

+ Own tissue so no immune responses

  • Donor site morbidity and loss of donor site function
  • Often not of sufficient strength

MAT300 (14 decks)

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