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Biomaterials Flashcards

(44 cards)

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1
Q

What are biomaterials?

A

Any material that is designed to interact with biological system for a medical purpose

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2
Q

Disadvantages for traditional treatments

A

Small molecule drugs - side effects, difficult to target site
Surgery - Drastic, invasive and damaging to surrounding tissues
Transplants - Lack of donors, chance of rejection

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3
Q

What are hydrogels?

A

3D ‘solid like’ networks that can hold large amounts of water in swollen scaffold (90-99% water)
Cross-linked network of hydrophilic polymers display elastic behaviours.

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4
Q

What are the 2 categories of cross-linking?

A

Chemical cross-linking - covalent bonds between polymer chains
Physical cross-linking - non-covalent interactions (VdW, ionic interactions, H-bonding, entanglement)

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5
Q

Common synthetic polymers used in hydrogels

A

Poly (ethylene glycol) (PEG)
Poly (2-hydroxyethyl methacrylate) (PHEMA)
Poly (vinyl alcohol) (PVA)

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6
Q

Properties of PEG

A

Chemically and biologically inert
Easily functionalised - tunable gel properties
Can be chemically cross-linked via range of different reactions

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7
Q

Properties of PHEMA

A

Monomer precursors often contaminated with difunctional monomer = spontaneous chemically crosslinked gel formation
High mechanical strength
Biocompatible + bioinert
Monomer = Highly toxic, needs to be removed

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8
Q

Properties of PVA

A

High elasticity
Mechanically weak
Highly biocompatible + bioinert
OH groups can be functionalised

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9
Q

Common properties for synthetic polymers

A

Bioinert
Low immunogenicity
Non-degradable
Easy to functionalise

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10
Q

Common natural polymers in hydrogels

A

Collagen
Alginate
Hyaluronic acid

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11
Q

Properties of Collagen hydrogel

A

High mechanical strength bc self assembled fibres
Bioactive bc peptide sequences (3 amino acids)
Cell adhesive and biocompatible as they mimic ECM
Biodegradable by enzymes in the body
Potential contaminants extracting collagen from animals

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12
Q

Properties of Alginate Hydrogel

A

Undergo gelation fast in presence of Ca2+ (ionic crosslinks)
Not cell adhesive
Requires modification of COOH with bioactive groups

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13
Q

Properties of Hyaluronic acid Hydrogel

A

Many growth factors
V bioactive
High charge density therefore high water content
Weak physically crosslinked gel

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14
Q

Common properties of natural polymer hydrogels

A

Inherently bioactive and biocompatible
Usually cell adhesive (not Aliginate)
Biodegradable

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15
Q

Mechanisms of Gelation

A

A + B strategy (add in crosslinker funtional group B to polymer functional group B)
AB strategy (Polymer has both functional groups attached)

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16
Q

Conditions for ideal crosslinking

A

Fast gelation
Non-toxic
Selective reactivity - no side reactions
Easy to do

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17
Q

Disadvantages of amide coupling

A

Poor selectivity
Slow
Susceptible to hydrolysis

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18
Q

Advantages of Thiol-ene coupling

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A

More selective
Can be fast
Non-toxic

19
Q

Cycloaddition between an azide and an alkyne

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A

Fast, selective and non toxic and easy to use
Also use ring strain to promote the cycloaddition but is difficult to synthesise

20
Q

What type of reactions are used for self healing gels

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A

Reversible reactions/ equilibrium

21
Q

Common dynamic linkages

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A

Imine - prone to hydrolysis
Hydrazone
Also small molecule gels dynamic as non-covalent bonds can break and reform

22
Q

How does electrospinning generate fibrous scaffolds

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A
  1. Solution of polymer through needle
  2. High voltage (+5000V)
  3. Electrostatic repulsion between charges overcome surface tension
  4. Droplet at end of needle stretch into Taylor cone
  5. Eject fine jet of liquid polymer
  6. Dry polymer collected on grounded plate
23
Q

Main 2 techniques of 3D printing

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A

Inkjet or extrusion printing
Stereolithography

24
Q

How does inkjet or extrusion printing work?

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A

Ink ejected through nozzle
Relatively cheap
Poor resolution - to access high res. need fast gelation

25
How does stereolithography work?
Light is used to convert a liquid ink into solid material, after laser used to write/draw material excess liquid can be washed away. Resolution is dictated by the resolution of the light source
26
Polyester fibres that can be spun or 3D printed
Poly (caprolactone) High biocompatability Good mechanical strength bc high crystallinity - strong non-covalent interactions Also Poly( lactic acid) and Poly(glycolic acid)
27
Advantages of using polyesters
Degradable by hydrolysis or enzymes Rate of breakdown crucial - stay long enough to serve purpose without being in body too long
28
Disadvantages of using polyesters
Toxicity of degredation products. Release of short chain COOH can raise tissue pH = inflammation
29
Young's Modulus
E (Pa) = stress(Pa)/strain(%) put material under stress and measure strain
30
Characterising properties of hydrogels
Rheology Electron Microscopy (EM)
31
What is Rheology?
Apply stress to materials to measure storage and loss modulus G' = Storage modulus, measures elasticity (Solid-like properties) G'' = Loss modulus, ability to flow under stres (Liquid-like properties)
32
How does Electron microscopy work?
Dehydrate Hydrogel to view 3D structure/ network - Cryo EM = freeze sample and remove solvent in vacuo then can view structure
33
How to make synthetic materials bioactive and cell adhesive
Functionalise with specific peptide sequences found in the ECM that make it cell adhesive Attach growth factors (ECM signalling proteins)
34
What are dynamic gels
Gels that form through a reversible reaction, so can break and reform bonds
35
Strategy to create a dynamic gel
1) Incorporate peptide based crosslinkers that cells can degrade when cells begin to grow - change scaffold 2) Light responsive hydrogel
36
What are matrix metalloproteinases
Proteases released by cells to breakdown the extracellular environment. Short MMPs can be used as crosslinkers in gel formation so cells can degrade hydrogel as they grow
37
What can light responsive hydrogels be used for?
1) Used to deprotect/ uncage a functional group so it can react 2) Degrade the scaffold by breaking chemical crosslinks between polymer chains
38
What is protein fouling?
When biomaterial placed into body exposed to soluble proteins and biomolecules - combo of non covalent forces leads to rapid protein adsorption onto surface. Composition of protein coating changes over time - smaller proteins replaced with larger. thermodynamically favourable
39
What are the disruptive effects from protein fouling
1) Block desired functionality via steric hinderance 2) Highlight material as immune threat 3) Activate undesired signalling pathways
40
How to resist protein fouling?
Using inert 'stealth' polymers: PEG, PVA or zwitterionic polymer Using a charged surface e.g. negatively charged surfaces resist binding of neg charged proteins
41
Beneficial protein binding
Growth factors - if bind to the ECM prevents degradation by cells and can extend signalling capabilities Collagen and hyaluronic acid are capable of sequestering growth factors - amplify biological response
42
Tissue-material interactions
Synthetic materials = Disrupt local tissue causing foreign body response Scaffolds based on natural polymers found in humans = no foreign body response
43
5 steps of foreign body response
1) Protein adsorption 2) Immune system activation - signalling and immune response activated, neutrophils arrive 3) macrophage invasion - inflammation, release enzymes + acid to try degrade material 4) Chronic inflammation + macrophage fusion - macrophages join together = foreign body giant cells 5) Fibrous encapsulation - Fibroblasts deposit collagen to surround material
44
Neg effects of foreign body response
Can completely negate any beneficial effects of a material or cause later issues e.g. blood clot

Materials (5 decks)

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