Miscellaneous Flashcards

1
Q
  1. Problems with current vascular grafts used clinically:

Autologous Grafts

Synthetic Grafts

Other?

A

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

Mechanical Properties (4)

Biological Properties (3)

Structural Requirements (4)

Clinical Requirements (3)

A

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
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3
Q
  1. Approaches to generate TE’d Vascular Grafts:
  • Natural Materials
    • Why it’s used
    • Technique to manufacture TEVGs
A

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
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4
Q
  1. Approaches to generate TE’d Vascular Grafts:
  • Synthetic Materials
  • Why it’s used
  • Technique to manufacture TEVGs
A

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
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5
Q
  1. Approaches to generate TE’d Vascular Grafts:
  • Compare:
    • Hybrid materials
    • Decellularisation
    • Self-assembly
  • Why it’s used
  • Technique to manufacture TEVGs
A

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

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