lecture 10 - hydrogels Flashcards
What is the definition of a hydrogel?
Hydrophilic polymer networks that are able to swell and retain large amounts of water and maintain 3D swollen structures
What are the main features of a hydrogel?
Viscosity - a liquid’s resistance to flow
Stiffness - mechanical properties of a solid, primarily the elasticity
Rheology - the study of flow and deformation in ‘shear’ - normally used to assess viscosity
What are some biomedical applications of hydrogels?
Contact lenses, face masks, face creams
Drug delivery - high retention rate and promotes diffusion upon trigger
Wound dressings - GranuGel is used as a filler to maintain a moist environment to promote wound healing
Implant coating - to provide a cell-friendly ‘envelope’ on devices
Regenerative medicine - e.g. decellularised gel products created from existing tissue
How can hydrogels be used in regenerative medicine (generally)?
Can form any geometry to fit wound size - can modify the shape of them; easily manipulated
Chemically and physically mimic the ECM - complex to recreate, as there are many different kinds of proteins/fibres
What are the properties/functions of the ECM?
Non-toxic
Mechanically stable/controlled degradation
Provide chemical and physical cues to the cells - different forces/movements
Support cells/guide tissues
Promote healing and tissue reconstruction
Integrate with native tissue
Promote functionality
Very difficult to replicate something so complex - not been done completely
What are some properties and examples of natural hydrogels?
Collagen, alginate, laminin, fibrin, agarose (from seaweed)
Decellularised tissue
`fibrous, non-toxic (mostly) and can be functionalism with cell-guiding cues
What are some properties and examples of synthetic hydrogels?
poly(lactic acid), calcium phosphate, poly(glycolic acid), peptides
can be designed (and therefore controlled)
no batch-to-batch variation
no sacrifice of animal
How can hydrogels be crosslinked to cause gelation?
Chemical cross linking - covalent bonds and other strong bonds
Physical - weak interactions, but potentially reversible
- a combination of methods can be used, particularly for composite systems
What are the properties of chemical, physical and dual gelation?
Chemical
- Strong/ permanent gelation
- More stable (mechanically) than physically crosslinked hydrogels
- Tunable degradation
- ‘Crosslinking agent’ potentially cytotoxic
Physical
- Does not require chemical crosslinking agent therefore potentially avoids cytotoxicity
- Triggered (temperature, pH etc.) and therefore greater control over gelation
- Potentially reversible
- Weak
Dual
- the best of both categories
- complex gelation (can help/hinder control over gelation)
Characterising hydrogel behaviour - what are the features of mechanical strength?
Tensile: deformation in stretch
Compressive: deformation through ‘crush’
Bend: deformation through flexion
Rheological: deformation in shear
Characterising hydrogel behaviour - what are the features of porosity?
How porous is the material, how big/small are the pores?
Characterising hydrogel behaviour - what are the features of degradation and biocompatibility?
- Loss of structure/mechanical strength – the breakdown once you have the 3D structure – losing the mechanical strength
- A cell will produce enzymes and will break some of the points, so we need to understand how long the gel will last, especially if drugs are introduced into it
- Cell response to material architecture and chemistry around them
- How cells affect hydrogel (do they accelerate the degradation?) – but also how the hydrogel affects the cells (dual relation)
- Inflammatory response
What factors need to be considered when selecting the right hydrogel?
using what we already have (ECM), do we need to modify it, do we need to create something from scratch, where do we start, can we create something complex enough?
How can decellularised hydrogels be used and what is their advantage?
Take a tissue and remove the DNA + cellular cues that make it belong to that particular species/patient
trying to use the architecture in a different context - less likely to produce an inflammatory response
difficult to recreate
however, they are expensive and there could be batch-to-batch variation
decellularise, mill into a powder, reconstitute as a hydrogel, new scaffold for cells, can form any geometry you desire, e.g. dorsal fin injury (dolphin)
How can de novo peptide hydrogels be used?
Difficult, but we can begin by trying to mimic protein secondary structure
Can study ECM proteins to understand how they form and create your own
ECM-like chemistry can be added (known as functionalisation or decoration)
Begin to control gel behaviour
E.g. can design a complementary coil that will be attracted to the first one and wrap around it to create a dimer - this will begin to create fibres
fine control over what AAs we introduce - can control cell behaviour
