Lecture 18 - Tissue engineering: novel materials Flashcards
What are the 3 key hurdles that we need to consider for TE success?
technical - what will talk about mostly. Suitable biomaterials, BS to 3d structures, delivery of biological signals, infection control
Commercial - can you get the funding? Financial problems
Regulatory - need to regulate, can be difficult, uncertainty in the field
The tradition Te approach of placing cells and growth factors into a matrix, and forming tissue does or doesn’t work?
Doesn’t work - body doesn’t respond well to a large foreign object placed in it, so the bio material being used is the hurdle
In vitro constructs is feasible for…
avascular, small or 2 dimensional tissues
so cartilage, skin have worked - no need to worry about blood supply
What is a n in vivo bioreactor?
allows construct develop concurrently with vascularisation
surgeons place a blood vessel loop in the side of the developing tissue
So the technical challenges are…
Suitable biomaterials,
BS to 3d structures,
delivery of biological signals, infection control
What is the role of the biomaterial used?
sacaffolds, surfaces and microenvironments for cell growth
ideally mimic native tissue ECM
provide space and biochemical environment to allow new tissue to grow
mechanics important as well as chemical and biochemical interactions
many criteria for good biomaterial apply, but good design may require..
compromise/optimisation
depending on the type of tissue, will determine what is prioritised
bicompatability is very…
specific, depends on application. Not appropriate as a broad descritpion
So what are the criteria for biomaterials in TE?
biocompatiblity
mechanical properties
biodegradability profile (time, strength and by-products)
suitable in vivo responses (e.g inflammation)
Ability to be fabricated into desired structures
cost-effective, available, regulatory approval
ability to be sterilised safely
adequate stability and shelf-life
promote desired cellular responses - proliferation, differentiation, gene expression
what are the limitations of the biomaterial in TE?
foreign body reaction, acid release, toxicity, supply, cost and reproducibility
lack of knowledge of design criteria - how quickly will the tissue grown how quickly will it degrade
lack of predictability of in vivo behavior and responses
Foregin body reactions, what are the steps?
1 Surgeon impants biomaterial
- the biomaterial absorbs a layer of proteins
- cell (neutrophils and macrophages) interrogate the biomaterial
- cells fuse to form giant cells and secrete cytokines
- In response to the cytokines, fibroblasts arrive and begin synthesising collagen
- The biomaterial is encapsulated in an acellular collagenous bag - need to avoid this
Layer-by-layer (lbl) assemblies - involves adding what to the polymer surface?
poly-electrolites
turns off macrophage interaction
combining inkjetting with thermally induced phase separation is beneficial as
Get even droplets of polymer solution
by shooting them into liquid nitrogen, freeze very quickly before they can join together
Can then coat with growth factors - gets a good slow release, suitable for delivering in a tissue engineering construct
Alpha-MSH is an anti-inflammatory peptide. How does it interact/ whats it’s significance?
a-MSH bnds strongly to hydrophobic surface
Good thing to coat the polymer microspheres with - reduces reaction with macrophages
The rate of release of growth factor (bFGF) and a-MSH can be independently controlled because
they vary in size
a_MSH = 13 residues
bFGF (growth factor) = 154 residues
