Lecture 18 - Novel Biomaterials Flashcards
Why is tissue engineering such an exciting field?
The loss of organs through disease, genetic mutation or trauma is a massive burden on the health system
Tissue engineering promises to:
• Alleviate shortage of organs
• Provide superior results
• New treatments for previously untreatable problems
However, despite this promise, there has been little progress to date
Why has there yet to be progress in the tissue engineering field?
1. Technical • Complex structure of tissue • Vascularisation • Development of suitable mimetic matrices • Infection • Delivery of biosignals
- Commercial
- Regulatory
Why are biomaterials so important in tissue engineering?
ECM plays many important roles:
• Structure and support
• Biological signals
• Replicates proper niche to stimulate cells to grow
• Creates a space for the growth of the new tissue
What are the criteria for biomaterials for use in TE?
- Biocompatability
- Mechanical properties of target tissues
- Suitable biodegradability profile
- Suitable in vivo responses
- Cost-effective
- Available
- Regulatory approval
- Able to be sterilised
- Adequate stability
- Promotes desired cellular responses
What are the difficulties that arise with biomaterials?
- Adverse reactions in the body (FBR, acid release, toxicity)
- Supply
- Cost
- Reproducibility
- Lack of knowledge
- Unpredictable in vivo behaviour
What is FBR?
Foreign body reaction
The normal reaction of a higher organism to an implanted synthetic material
This limits the function of the implanted material
Process:
- Implantation
- Biomaterial gains protein layer
- PMNs and macrophages interrogate the biomaterial
- Inflammatory cells fuse to form giant cells which release cytokines
- Recruitment of fibroblasts which secrete collagen
- Biomaterial encapsulated in an acellular collagen capsule
The collagen capsule does not allow the movement of cells into the new tissue
What are PLGA scaffolds?
This is a type of polymer scaffold
Describe how growth factors may be delivered to tissue
Why is controlled release of GFs preferable?
Controlled release of GFs through:
- Gelatin microspheres
- Benefits:
• Size, shape easy to control
• Control of mechanical and chemical properties
• Binds many GFs
• Achieved release over 3 weeks - Scaffolds
- Nanospheres
- Nanofibres
- Nanoporous materials
Controlled release of GFs has been shown to result in more tissue growth
This is because GFs are not stable molecules, and if not released in a controlled way, they do not persist for a long time
What are in vivo bioreactors?
Growth of new tissue within the body (as opposed to in vitro)
This could possibly help the problem of vascularisation
Process:
- Plastic container + blood vessel loop implanted in the body
- Due to the hypoxic environment, blood vessels and capillaries start to sprout from this initial blood vessel loop
In this way, the tissue could be grown inside the body and have its own blood supply from the start
How can the FBR be prevented?
Instead of using a different material (because the material might have all the mechanical properties that we want), one can re-surface the material
LbL: Layer-by-Layer processing
Process:
• Hydrolysis and addition of amino groups
• Poly-electrolytes (Hyaluronic acid and Chitosan) layered onto the material
• This is repeated for 50-100 layers
• Layers cross-linked with Carbodiimide (EDC) (keeps the molecules in place)
Ideally, the body now will not recognise the material as a foreign object
What is LbL?
Layer by layer processing: layers of molecules are coated onto the biomaterial
This can minimise FBR
How are porous microspheres produced?
Custon inkjet printing system
The liquid polymer is released in uniform droplets into liquid nitrogen, which freezes them very quickly.
This creates the porous beads
The beads can then be coated (LbL)
as well as the addition of GF, e.g. FGF-2, in between layers
This creates a structure that delivers controlled release of GFs
What is alpha-MSH?
How is it being used?
a-MSH: Anti-inflammatory peptide
Initial attempt:
a-MSH was coated onto polymer beads for slow release, however, most of a-MSH was released in the first 3 days
Further research: To determine which sort of reactions between the peptide and the surface of the polymer were optimal • Hydrophobic coating? • Positive charge? • Negative charge?
Second attempt:
With the controlled release of a-MSH, there was less of an inflammatory response when the material was implanted
Furthermore, it has been used in microbeads in conjunction with FGF-2
When FGF and a-MSH are delivered together, what things need to be considered?
FGF-2 is a bigger molecule than a-MSH, so will thus move through the polymer layers differently
The release of the two molecules can be controlled through altering:
• Extent of cross linking
• Number of layers
How can the problem of infection be averted?
It is difficult to ensure sterility of biomaterials
Sol-gel process:
• Coat biomaterial with nano particles (e.g. silver) onto different types of constructs, acts as an anti-microbial
• This inhibits the growth of bacteria on the implanted material
• (increasing the amount of Ag results in decreased CFU of bacteria)
