Abstract

The vascular transplantation is an established therapy for vascular diseases by replacing or bypassing the damaged blood vessel with a functional vascular graft. Autologous blood vessels are considered as the gold standard grafts for vascular transplantation, but the limited tissue source and the high morbidity associated with tissue harvesting have restricted their therapeutic potential. Vascular tissue engineering represents an alternative solution to replace the autologous blood vessels by developing an artificial conduit which can closely mimic the nature blood vessel. However, clinical trials with small vascular grafts are disappointing. The aim of this study is to investigate the feasibility of constructing a small vascular graft from the decellularized amniotic membrane (DAM graft) via different crosslinking methods. The human amnion membrane was decellularized, trimmed into 5 cm x 8 cm rectangular shape, and rolled around a catheter (diameter =1.2 mm) to make the primary DAM graft. Each of the resulting conduits was additionally crosslinked with: a) 0.1% glutaraldehyde; b) 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (20mM) / N-hydroxy succinimide (10mM) (EDC-NHS); c) 0.5% genipin; and d) no-crosslinking as control group. Our results demonstrated the structural integrity, material stability, mechanical behaviors, and biocompatibilities of the DAM grafts can be modified by the chemical crosslinking treatment. In which, the genipin crosslinked DAM graft exhibited the most integrated layered structure. Its level of material stability was comparable to those of the glutaraldehyde and the EDC-NHS crosslinked DAM grafts. Furthermore, the genipin crosslinking did not significantly affect the mechanical properties of the DAM graft. The genipin-crosslinked DAM graft was further tested in vivo by implanting it in a rat abdominal aorta replacement-model. All rats implanted with the genipin-crosslinked DAM graft exhibited a blood vessel patent up to 9-month post-implantation. In conclusion, we represented a potential avenue to construct a flexible vascular graft that has the patient-specific dimension and meet specific demands for biological and mechanical performance criteria by using the DAM followed by lyophilization and the genipin.

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