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Biomaterials > Topic 1 - Biocompatibility/Biodegradation > Flashcards

Topic 1 - Biocompatibility/Biodegradation Flashcards

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1
Q

What is the definition of biocompatibility?

A

the ability of a material to perform its desired functions with respect to a medical therapy
to induce an appropriate host response in a specific application and to interact with living systems without having any risk of injury, toxicity or rejection by the immune system and undesirable or inappropriate local or systemic effects.

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2
Q

How can the concept of biocompactibility be divided?

A

1 - biosafety
2 - biofunctionality

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3
Q

What is biosafety?

A

materials do not, either directly or through the release of their material consistent: produce adverse local or systemic effects, be carcinogenic, or produce adverse reproductive and developmental effects

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4
Q

What is biofunctionality?

A

the performance of a given material in application to a particular tissue/organ

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5
Q

What is cytotoxicity?

A

refers to the damages to cells (such as DNA damage or permeabilization of the cellular membrane) due to harmful chemicals released by the biomaterial or degradation products of the biomaterial.

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6
Q

What is the direct contact method test?

A

A piece of material is placed directly on a monolayer of cells and incubated for a period of time, after which the cells are observed for signs of cytotoxicity.

mostly water based environment so if material is water soluble it is not suitable
release of chemicals? - problem with surface or mechanical properties

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7
Q

What is the extraction method test?

A

incubate the test material in a medium (water), as you extract and test, check if there is a release of drugs

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8
Q

What are the 2 control systems for cell viability?

A

1 - expect high percentage = non toxic
2 - expect low percentage = toxic

can be more than 100%

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9
Q

How can you measure cell adhesion and spread through biocompatibility?

A

by maintaining the culture for long periods of time, the influence of the substrate on cell viability, function and motility can also be determined.

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10
Q

What is cell staining?

A

a technique that can be used to better visualise cells and cell components under a microscope

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11
Q

What is DAPI?

A

a fluorescent nuclear stain that is excited by ultraviolet light
showing blue florescence when bound to DNA. can be used in living of fixed cells

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12
Q

What is Phalloidin?

A

a fluorescent stain to localise actin filaments in living or fixed cells (cell motility)

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13
Q

Advantages of in vitro studies

A
  • the experimental conditions can be strictly controlled with no limitation in the number of experiments that can be performed
  • consistency and reproducibility of the results
  • better understanding of the effects of a particular compount on a specific cell type
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14
Q

Disadvatages of in vitro studies

A
  • a static system that does not consider organ-specific functions
  • no evaulation of effect on organ/tissue interactions
  • cell characteristics can change during the test
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15
Q

What are in vivo studies?

A

performed on whole, living organisms
animal models are used to stimulate and predict the clincial behaviour, safety and biocompaitibility of medical devices in humans

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16
Q

Example animals of short term implantation

A

mice, rats, guinea pigs

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17
Q

Example of animals of long term testing in subcanteous tissue, muscle or bone

A

rats, guinea pigs, dog, sheep, goats and other animals with relatively longer life spans

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18
Q

Advantages of in vivo studies?

A
  • evaluation of effects on organ/tissue interactions
  • control the exposure dose to chemicals at identified periods in the animals development
  • chronic exposure can be studied (life time exposure)
  • specific animal models can be studied
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19
Q

Disadvantages of in vivo studies?

A
  • biochemical differences between animals and humans make data extrapolation difficult
  • lack of standardization
  • test in animals do. not perfectly predict results in humans
  • ethical issues
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20
Q

What is a foreign body response?

A

the implantation of a foreign object inside the human body activates complex signalling cascades, which can lead to biological encapsulation of implant
it is the reaction of the host system to a foreign object

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21
Q

What happens if the tissue responsed badly to a foreign body?

A

They are surrounded by collagen deposition in the form of a fibrotic scar at the material tissue interface
this actively isolates the implant from the rest of the body preventing integration and vascularisation of the implant

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22
Q

What is acute inflammation?

A

white blood cells converge on the site, attempting to degrade the implant

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23
Q

What is chronic inflammation?

A

macrophages surrounding the biomaterial and potentially forming foreign body giant cells.

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24
Q

Process of foreign body response

A

1 - blood proteins rapidly absorb to the biomaterial surface, triggering blood coagulation
2 - acute inflammation
3 - chronic inflammation
4 - fibroblasts and new blood vessels might envelop the area, leading to the formation of granulation tissue
5 - a thick fibrous tissue capsule could form around the implant (FBR)

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25
What material properties affect foreign body response?
- design of implant - elastic modulus - surface chemistry
26
How does design of implant affect FBR?
sharp tips and edges lead to elevated local strains and should be avoided in implant design , as sharp discontinuities can cause severe tissue damage
27
How does elastic modulus affect FBR?
a mismatch in mechanical properties can lead to problems. for exmaple in soft tissues a material with an elastic modulus higher then the tissue will not lead to a higher foreign body reponse but will also cause pain
28
How does surface chemistry affect FBR?
non specific adsorption of biomolecules surfaces is critical in deciding the tissue response.
29
Examples of polymers with late degradation tissue response
- PLGA - PLA - PGA - biodegradation
30
Disadvantages of PLGA, PLA, PGA
- they release lactic acid and glycolic acid, which are not benign and can invoke an inflammatory response this may be acceptable when the implanted polymer is low in amount however not accepted for larger implants such as bone screws or implants
31
How can the unfavourable inflammatory repsonses cause by PLA. PGLA and PCL etc be controlled?
- hydroxyapatite - beta-tricalcium phosphate - magnesium hydroxide - coatings containing antinflammatory drugs
32
What occurs during protein absorption?
local tissue and proteins will adhere to the material surface the magnitude of protein absorption is highly dependant on type of material used increased by surface roughness greater porositycan induce greater protein adhesion as well as the specificty of proteins that adhere to the surface
33
What occurs during neutophil migration?
neutrophils are the first immune cell to infiltrate the material surface and act as the primary cell population during acute inflammation tissue damage from implantationm recognition of the foreign body repsonse and/or bacterial infection may initiate neutrophil migration
34
What occurs during chronic inflammation?
persists for 2-3 weeks with local responses from macrophages pore sizes of around 30-40 micrometers in diameter yeild greater pro-healing immune cell reponses at the material surface have been associated with greater vascularisation, a reduced fibrous capsule and greater tissue integration
35
What occurs during giant foreign body cell formation?
multi-nucleated FBGCs form by the fusion of macrophages at the biomaterial surface
36
What occurs during the fibroblast cell migration - collagen capsule formation?
fibroblasts migrate to the surface of the biomaterial and generate ECM proteins like collagen fibrous capsule generates around the biomaterials and become encapsulated benefits of increased pore size on pro-healing and angiogenic repsonses.
37
Definition of biodegradation
the breakdown of a material due to the environmental factors that it is exposed to
38
What are the 2 types of biodegradation?
- passive - active
39
What is passive biodegradation?
where the biomaterial degrades due to the influence of the environment that surrounds it, without interplay with cellular processes
40
What is active biodegradation?
where the degradation products themselves trigger a host cell response, which then actively contributes to degradation
41
Examples of biodegradable metals
- iron - zinc - magnesium based alloys these are expected to degrade or corrode gradually in vivo after performing their supportive assisting functions during tissue healing or diease diagnosis, under the influence of appropriate host responses
42
Iron - based Advantages
- high elasticity - high ductility
43
Iron - based Disadvantages
- slow biodegradation rate - ferromagnetic nature
44
Zinc based Advantages
- favourable degradation rates
45
Zinc based Disadvantages
- poor strength and ductility
46
Magnesium based Advantages
- lightweight - density close to that of cortical bone - mechanical properties close to that of human bone
47
Magnesium based Disadvantages
- fast corrosion with deterioration of mechanical properties - generation of hydrogen gas during degradation: can enter blood stream and interfere with tissue healing
48
Examples of biodegradable bioceramics and glasses
- amorphous hydroxyapaptite - amorphous calcium phosphates - silicate glasses and glass cermamics
49
What is the process of phagocytosis?
ion exchange between implants and dissolved moieties in aqueous biological environments breaks down materials into finer pieces. small sized particles can be cleared by cells or until ions are dissolved into body fluids solution and drained by the vascular system
50
What are the physiochemical factors that influence degradation?
1 - crystalline features 2 - physical structure/geometry 3 - presence of addictives of mineral origins 4 - chemistry 5 - surface reactivity
51
How does crystalline features influence degradation?
the higher the crystallinity, the lower the degradation kinetics. amorphous biomaterials dissolve faster than crystalline ones
52
How does physical structure/geometry affect degradation?
the larger the exposed surface to the solution environment, the faster the biomaterial dissolves ,simply because solid-liquid exchanges take place
53
How does presence of additives affect degradation?
carbonate, silicate or stontium added to HA to accelerate the dissolution carbonate or other ions in CaP to stimulate the carbonic anhydrase activity zinc and fluoride in CaP to inhibit osteoclastic resorption in vitro and in vivo.
54
How does chemistry affect degradation?
ionic bonds tend to dissolve better in aqueous solutions, with some exceptions such as calcium carbonate
55
How does surface reactivity affect degradation?
the reactivity of the surface will influence proteins absorption, cell interaction including signalling and adhesion, chemical interactions
56
Examples of synthetic biodegradable polymers
- polyesters, polycarbonates, polyurethanes
57
Examples of natural biodegradable polymers
- those derived from proteins, polyasccharides, or nucleic acids
58
What can degradation result in?
- bond scission and subsequent chemical transformation - changes in molecular weight - deterioration of functionality
59
What is chemical degradation?
chain cleavage through hydrolysis - abiotic hydrolysis - enzyme - promotes hydrolysis
60
What is hydrolysis?
the process by which vulnerable bonds in a polymer chain react with water molecules and break, resulting in shorter chains and polymer degradation
61
What bonds should there be for hydrolysis to occur?
polymer should contain hydrotically unstable bonds - ester groups - urethane groups - carbonate groups
62
What does the rate of hydrolysis depend on ?
- polymer chain length - Mw distribution - crytallinity - porosity etc
63
How does degradation rate change with Mw?
rate increases as molecular weight increases as a consequence of the accessibility of functional groups for the degrading species.
64
How does crystallinity affect degradation?
crystalline domains resist the infiltration of the degrading species due to densly packed polymer chains degradation is faster in amorphous regions of semicrystalline polymers
65
How does glass transition temperature affect degradation?
at temperatures above Tg of the polymer, a more rapid diffusion of degrading species occurs
66
What is surface erosion?
degradation reactiobs are limited to the surface of the polymer material and occur at a significantly higher rate relative to diffusion rate of water into the bulk the size and mass of polymers decrease over time while molecular weight and mechanical properties remain unchanged
67
What is bulk erosion?
occurs uniformly throughout polymer Water penetrates the polymer at a faster rate than it is broken down the polymer becomes hydrated and cleavage bonds present in the amorphous regions causes a decrease in molecular weight, leads to a reduction in mechanical properties
68
What is autocatalysis?
affects bulk erosion rate and causing the material to degrade in a heterogeneous matter. degradation products near the surface can be more easily eliminated. product at the centre are unable to diffuse away resulting in locialized acidic environment. the increased acidity induces acceleraion degradation at the centre pof the material while surface continues to degrade at orginal rate.

Biomaterials (4 decks)

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