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.

Bio-safe processing of polylactic-co-caprolactone and polylactic acid blends to fabricate fibrous porous scaffolds for in vitro mesenchymal stem cells adhesion and proliferation

“…In particular, PLC scaffolds stiffness can be increased in more than one order of magnitude by the presence of 50% of PLA. The strengthening effect of PLA is also consistent with the results recently reported by Wang and co-workers for PLC/PLA porous scaffolds prepared by TIPS [41].…”

“…As shown in the results of X-ray analysis, PLC diffraction peaks exclusively correspond to the crystallization of PLA because of the rather low CL molar composition of the PLC used in this work [37]. The addition of PLA to PLC, even at the lowest concentration of 10 wt%, turns the morphology of PLC from globular to an almost random nano-size scale fibrous structure, in agreement to the results reported in [41].…”

“…This represents a unique result as, so far, it has been reported that processing PLC solutions by means of TIPS do not enable the fabrication of nano-size scale fibers, because of difficulties in polymer crystallization [41,42].…”

Generation and Assessment of Functional Biomaterial Scaffolds for Applications in Cardiovascular Tissue Engineering and Regenerative Medicine

“…Wang et al covalently linked heparin as an anticoagulant to a thermally induced phase separated scaffold made of PLLA and poly (l‐lactide‐co‐ε‐caprolactone) (PLCL). Interestingly, the scaffold enabled endothelial cell attachment, but showed low protein attachment, which is important to avoid stenosis, thrombus or neointima formation . Another strategy for designing an acellular but functional scaffold for blood vessel replacement is the application of structural ECM components, such as collagens and elastin .…”

Biomaterial‐Induction of a Transplantable Angiosome

“…Given the overarching importance of being able to induce luminal sprouting from major blood vessels within a defined volume in order to sustain regenerating tissue volumes, surprisingly little has been published on interaction between biomaterials and major (milli‐scale) blood vessels. Most prior work has focused on blood‐material interactions to develop nonthrombosing artificial blood vessels . However some literature examines the effect of materials placed around blood vessels as external stents.…”