OE L36 Tissue Engineering 2

Question 1

What are the 4 domains of guidance cues which regulate tissue regeneration?

Answer 1

• Physical: cell-cell contact, topographic cues
• Chemical: GFs and other chemoattractants
• Haptotactic: ECM
• Electrical

All of these guidance cues interact to regulate the cellular responses with leads to things such as wound healing tissue regeneration and embryonic development.

Question 2

How do cells know which direction to migrate in at a cellular level?

Answer 2

• Variety of signalling pathways, e.g. GPCR and GFs regulate downstream effectors such as cytoskeletal rearrangement, cell adhesion, angiogenesis
• Lamellipodia at leading edge of motile cells pulls the cell forward during migration- chemotaxis

Question 3

How does the ECM influence cell activity e.g. migration etc.

Answer 3

ECM stores, displays and releases GFs, GFs are linked to cellular activity.

Question 4

How does GF delivery influence cell proliferation and migration?

Answer 4

• Prolonged availability of GFs at the defective site allows migration of cells to the area of injury for proliferation and differentiation
• Concentrations of GFs at the wound must be appropriately localised, sustained and released
• GFs must be delivered on a biologically acceptable scaffold which degrades appropriately (Speed of degradation of biomaterial dictates time availability of growth factors.)
• Scaffold should maintain space for tissue formation to occur

Question 5

What are the 3 categories of matrix material?

Answer 5

• Inorganic carrier material
• Synthetic polymers
• Natural polymers

Question 6

Are inorganic carrier materials successful in aiding tissue enginnering?

Answer 6

No.

They have been extensively researched with poor results. E.g. calcium phosphate ceramics.

Question 7

Are synthetic polymers a suitable material in tissue engineering?

Answer 7

Yes, they are easily accessible and are being thoroughly researched.
E.g. Polylactide (PLA), polyglycolide (PLG)

Question 8

Are natural polymers a suitable material in tissue engineering?

Answer 8

Yes, they are non-toxic and derived from animal or plants e.g. Z1212/Telethonin complex, gelatine, fibrin, hyauronic acid, chitosan.
However, they are of low purity and there are issues surrounding contamination with unknown factors.

Question 9

What are the 2 methods of degradation of matrix materials?

Answer 9

• Chemical clocks: programmed degradation at a controlled rate
• Based on bioactivity: degradation proceeds alongside healing response via enzymatic activity- cell controlled degradation rate

Question 10

Describe hSAF hydorgels.

Answer 10

• Human self-assembling fibrous hydrogels
• Simple structures
• No/low cell toxicity
• Biodegradable
• Can incorporate regularly spaced functional groups
• Offers low production yield and expensive

Question 11

Describe PDMS microchamber arrays.

Answer 11

• Stem cells in each pocket

- Directly placed onto damaged area of brian, used in complex surgery

Question 12

What are the effects of scaffold porosity on cellular activity?

Answer 12

• If pores are too large, cells won’t be able to survive

- If pores are too small, they won’t have sufficient nutrients or enough space to proliferate

Question 13

What are BMPs?

Answer 13

Soluble, local acting signalling molecules

• Turn mesenchymal stem cells into carilage or bone forming cells
• Initiate MSC infiltration, differentiation of cells, cartilage resoprtion and bone formation, bone remodelling

Question 14

What are the 2 types of gene therapy?

Answer 14

• Non-viral: uses naked DNA, liposomes and polymer-DNA complexes, “gene gun method”
• Viral: uses adeno viruses/herpes virus/retrovirus