Biomaterials Flashcards
What are biomaterials?
Any material that is designed to interact with biological system for a medical purpose
Disadvantages for traditional treatments
Small molecule drugs - side effects, difficult to target site
Surgery - Drastic, invasive and damaging to surrounding tissues
Transplants - Lack of donors, chance of rejection
What are hydrogels?
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.
What are the 2 categories of cross-linking?
Chemical cross-linking - covalent bonds between polymer chains
Physical cross-linking - non-covalent interactions (VdW, ionic interactions, H-bonding, entanglement)
Common synthetic polymers used in hydrogels
Poly (ethylene glycol) (PEG)
Poly (2-hydroxyethyl methacrylate) (PHEMA)
Poly (vinyl alcohol) (PVA)
Properties of PEG
Chemically and biologically inert
Easily functionalised - tunable gel properties
Can be chemically cross-linked via range of different reactions
Properties of PHEMA
Monomer precursors often contaminated with difunctional monomer = spontaneous chemically crosslinked gel formation
High mechanical strength
Biocompatible + bioinert
Monomer = Highly toxic, needs to be removed
Properties of PVA
High elasticity
Mechanically weak
Highly biocompatible + bioinert
OH groups can be functionalised
Common properties for synthetic polymers
Bioinert
Low immunogenicity
Non-degradable
Easy to functionalise
Common natural polymers in hydrogels
Collagen
Alginate
Hyaluronic acid
Properties of Collagen hydrogel
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
Properties of Alginate Hydrogel
Undergo gelation fast in presence of Ca2+ (ionic crosslinks)
Not cell adhesive
Requires modification of COOH with bioactive groups
Properties of Hyaluronic acid Hydrogel
Many growth factors
V bioactive
High charge density therefore high water content
Weak physically crosslinked gel
Common properties of natural polymer hydrogels
Inherently bioactive and biocompatible
Usually cell adhesive (not Aliginate)
Biodegradable
Mechanisms of Gelation
A + B strategy (add in crosslinker funtional group B to polymer functional group B)
AB strategy (Polymer has both functional groups attached)
Conditions for ideal crosslinking
Fast gelation
Non-toxic
Selective reactivity - no side reactions
Easy to do
Disadvantages of amide coupling
Poor selectivity
Slow
Susceptible to hydrolysis
Advantages of Thiol-ene coupling
More selective
Can be fast
Non-toxic
Cycloaddition between an azide and an alkyne
Fast, selective and non toxic and easy to use
Also use ring strain to promote the cycloaddition but is difficult to synthesise
What type of reactions are used for self healing gels
Reversible reactions/ equilibrium
Common dynamic linkages
Imine - prone to hydrolysis
Hydrazone
Also small molecule gels dynamic as non-covalent bonds can break and reform
How does electrospinning generate fibrous scaffolds
- Solution of polymer through needle
- High voltage (+5000V)
- Electrostatic repulsion between charges overcome surface tension
- Droplet at end of needle stretch into Taylor cone
- Eject fine jet of liquid polymer
- Dry polymer collected on grounded plate
Main 2 techniques of 3D printing
Inkjet or extrusion printing
Stereolithography
How does inkjet or extrusion printing work?
Ink ejected through nozzle
Relatively cheap
Poor resolution - to access high res. need fast gelation
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
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)
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
Disadvantages of using polyesters
Toxicity of degredation products. Release of short chain COOH can raise tissue pH = inflammation
Young’s Modulus
E (Pa) = stress(Pa)/strain(%)
put material under stress and measure strain
Characterising properties of hydrogels
Rheology
Electron Microscopy (EM)
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)
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
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)
What are dynamic gels
Gels that form through a reversible reaction, so can break and reform bonds
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
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
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
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
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
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
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
Tissue-material interactions
Synthetic materials = Disrupt local tissue causing foreign body response
Scaffolds based on natural polymers found in humans = no foreign body response
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
Neg effects of foreign body response
Can completely negate any beneficial effects of a material or cause later issues e.g. blood clot
