Miscellaneous

Question 1

1. Problems with current vascular grafts used clinically:

Autologous Grafts

Synthetic Grafts

Other?

Answer 1

Autologous Grafts

• veins commonly used
• limited availability of arteries
• invasive harvest - donor site morbidity = increased susceptibility to infection (sepsis)
• damaged endothelial cell lining can lead to thrombosis
• mismatch in suture line stress concentrations between native and new graft

Synthetic Grafts

• eg Dacron, Teflon
• good for large to medium diameter vessels >6mm, but not small diameter
• no endothelial cells
• mechanical mismatch (sometimes

Other

• neointimal hyperplasia (SMC infiltration) can lead to poor patency rates
  *

Question 2

2. Requirements for a TE’d Vascular Graft that solves current clinical issues?

Mechanical Properties (4)

Biological Properties (3)

Structural Requirements (4)

Clinical Requirements (3)

Answer 2

Mechanical Properties

• must be able to withstand normal physiological blood pressures, 80-120 mm Hg
• burst strength - resistance to rupture; reflects tensile strength and extensibility
• similar compliance to native vessel
• fatigue resistant

Biological Properties

• biocompatible - non-cytotoxic
• non-immunogenic
• promotes endothelial cell growth (for non-thrombogenicity) and minimises neointima formation; smc migration to the surface

Structural Requirements

• replicate different layers of arteries (intima, media, adventitia)
• similar dimensions + surface properties to native blood vessels to prevent blood flow disturbances (haemodynamically compatible)
• consistent composition and structure in fabrication
• can’t leak

Clinical Requirements

• easy to handle
• good shelf-life
• functions immediately upon implantation

Question 3

3. Approaches to generate TE’d Vascular Grafts:

• Natural Materials
  
  • Why it’s used
  • Technique to manufacture TEVGs

Answer 3

Fibrin

• fibrinogen laid down by platelets to form a clot -> haemocompatible, biocompatible, found natively in the body
• technique: gelled with encapsulated cells using a mould

Silk

• from silkworms; biocompatible; stretchy, strong
• technique: electrospinning

Collagen

• found natively in the ECM; can modify fibre density, orientation, add crosslinks
• technique: gelled with encapsulated cells using a mould

Question 4

4. Approaches to generate TE’d Vascular Grafts:

• Synthetic Materials
• Why it’s used
• Technique to manufacture TEVGs

Answer 4

Teflon (PTFE)

• potentially haemocompatible and less thrombogenic - blood won’t stick as much
• technique__: moulding

Dacron

• can withstand pressures, liquid won’t stick to it as much
• technique: moulding; electro

PCL, PLA, PGA

• mechanically strong, biocompatible, biodegradable
• technique: electrospinning

Question 5

5. Approaches to generate TE’d Vascular Grafts:

• Compare:
  
  • Hybrid materials
  • Decellularisation
  • Self-assembly
    ​
• Why it’s used
• Technique to manufacture TEVGs

Answer 5

Hybrid - combination of natural and/or synthetic materials

• combine desirable properties of both materials
• eg PCL + elastin was electrospun on a rotating mandrel and created a layered tubular construct, which was then seeded with HUVECs

Decellularisation - sources: allogeneic and xenogeneic (large mammals eg pigs, sheep, cows, dogs)

• retain hierarchical structure of ECM found in native blood vessels; has native ECM components
• technique: repopulate with ECs and SMCs

Self-assembly - cultured cell sheets

• uses autologous cells - non-immunogenic response; mimics layered structure of arteries
  
  • problem: takes a long time to develop
• technique__: take cells from patient, culture them to form sheets of cells such as fibroblasts and SMCs, wrap cell sheets around a mandrel to form a hollow tube

Also consider 3D printing, microtissue cell aggregates….

Bioreactors can also be used for biomimetic mechanical stimulation, eg circumferential distention, axial stretch and luminal blood flow