Miscellaneous Flashcards
- Problems with current vascular grafts used clinically:
Autologous Grafts
Synthetic Grafts
Other?
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
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- Requirements for a TE’d Vascular Graft that solves current clinical issues?
Mechanical Properties (4)
Biological Properties (3)
Structural Requirements (4)
Clinical Requirements (3)
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
- Approaches to generate TE’d Vascular Grafts:
-
Natural Materials
- Why it’s used
- Technique to manufacture TEVGs
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
- Approaches to generate TE’d Vascular Grafts:
- Synthetic Materials
- Why it’s used
- Technique to manufacture TEVGs
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
- Approaches to generate TE’d Vascular Grafts:
- Compare:
- Hybrid materials
- Decellularisation
-
Self-assembly
- Why it’s used
- Technique to manufacture TEVGs
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