Heparinized PLLA/PLCL nanofibrous scaffold for potential engineering of small-diameter blood vessel: tunable elasticity and anticoagulation property.

Abstract

The success of tissue engineered vascular grafts depends greatly on the synthetic tubular scaffold, which can mimic the architecture, mechanical, and anticoagulation properties of native blood vessels. In this study, small-diameter tubular scaffolds were fabricated with different weight ratios of poly(l-lactic acid) (PLLA) and poly(l-lactide-co-ɛ-caprolactone) (PLCL) by means of thermally induced phase separation technique. To improve the anticoagulation property of materials, heparin was covalently linked to the tubular scaffolds by N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide coupling chemistry. The as-prepared PLLA/PLCL scaffolds retained microporous nanofibrous structure as observed in the neat PLLA scaffolds, and their structural and mechanical properties can be fine-tuned by changing the ratio of two components. The scaffold containing 60% PLCL content was found to be the most promising scaffold for engineering small-diameter blood vessel in terms of elastic properties and structural integrity. The heparinized scaffolds showed higher hydrophilicity, lower protein adsorption ability, and better in vitro anticoagulation property than their untreated counterparts. Pig iliac endothelial cells seeded on the heparinized scaffold showed good cellular attachment, spreading, proliferation, and phenotypic maintenance. Furthermore, the heparinized scaffolds exhibited neovascularization after subcutaneous implantation into the New Zealand white rabbits for 1 and 2 months. Taken together, the heparinized PLLA/PLCL nanofibrous scaffolds have the great potential for vascular tissue engineering application.