The development of an elastomeric scaffold for small diameter blood vessel tissue engineering
Ilagan, Bernadette Gillian
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In coronary artery bypass surgery the autologous saphenous vein is the most commonly used vascular graft. However, in a growing number of patients this vein is not available due to disease or availability. To date, there are no commercially available vascular grafts to replace the autologous saphenous vein. Nevertheless, it is widely accepted that a successful small diameter blood vessel alternative will be found using a tissue engineering approach. A photo-cross-linked biodegradable elastomer of acrylated star-poly(ε-caprolactone-co-D,L-lactide) (ASCP) has recently been developed. The elastomer possesses many desirable properties, such as manufacturability and mechanical properties, making it an interesting scaffolding material candidate for this application. To test the feasibility of the ASCP elastomer as a scaffolding material, a porous scaffold with 90% porosity was constructed using paraffin microbeads combined with an emulsion of ASCP prepolymer and water. Native arterial mechanical properties were matched with an 1800 Da ASCP elastomeric scaffold (ELAS 1800) having 85% porosity. In vitro degradation of scaffolds prepared with two different ASCP Mn (1800 and 4500 Da) was investigated for 8 weeks. Bulk hydrolysis was the mode of degradation regardless of configuration, with the porous scaffold degrading slower than the nonporous control. In addition, the ELAS 4500 scaffold also degraded faster than the ELAS 1800 scaffold with the same porosity. In order to promote the cellular response to this potential vascular scaffold, the surface of the elastomer was modified to enhance bovine coronary artery smooth muscle cell (SMC) attachment and proliferation. Base etching the surface was not as effective as adding a small peptide sequence Gly-Arg-Gly-Asp-Ser (GRGDS) known to enhance cell adhesion. The surface modifications did not change SMC phenotype as all surfaces expressed the contractile marker proteins smooth muscle α-actin and h-caldesmon. The SMCs also expressed these marker proteins when seeded on porous scaffolds. Finally, it was possible to integrate the porous scaffold into a biomimetic blood vessel design. With this initial testing, it appears that the ASCP elastomer is a feasible scaffolding material for small diameter blood vessel tissue engineering. Nevertheless, more detailed testing of mechanical properties and cell behaviour must be conducted to ascertain that the ASCP elastomer and the proposed biomimetic blood vessel design can be appropriate replacements for the autologous saphenous vein.