Fabrication of small-diameter vascular scaffolds by heparin-bonded P(LLA-CL) composite nanofibers to improve graft patency

Abstract

Abstract:The poor patency rate following small-diameter vascular grafting remains a major hurdle for the widespread clinical application of artificial blood vessels to date. Our previous studies found that electrospun poly(L-lactide-co-epsilon-caprolactone) (P[LLA-CL]) nanofibers facilitated the attachment and growth of endothelial cells (EC), and heparin incorporated into P(LLA-CL) nanofibers was able to release in a controlled manner. Hence, we hypothesized that heparin-bonded P(LLA-CL) vascular scaffolds with autologous EC pre-endothelialization could significantly promote the graft patency rate. To construct a small-diameter vascular scaffold, the inner layer was fabricated by heparin-bonded P(LLA-CL) nanofibers through coaxial electrospinning, while the outer layer was woven by pure P(LLA-CL) nanofibers. Except dynamic compliance (5.4 ± 1.7 versus 12.8 ± 2.4 × 10 −4 /mmHg, P , 0.05), maximal tensile strength, burst pressure, and suture retention of the composite, scaffolds were comparable to those of canine femoral arteries. In vitro studies indicated that the scaffolds can continuously release heparin for at least 12 weeks and obtain desirable endothelialization through dynamic incubation, which was confirmed by EC viability and proliferation assay and scanning electronic microscopy. Furthermore, in vivo studies demonstrated that pre-endothelialization by autologous ECs provided a better effect on graft patency rate in comparison with heparin loading, and the united application of pre-endothelialization and heparin loading markedly promoted the 24 weeks patency rate of P(LLA-CL) scaffolds (88.9% versus 12.5% in the control group, P , 0.05) in the canine femoral artery replacement model. These results suggest that heparin-bonded P(LLA-CL) scaffolds have similar biomechanical properties to those of native arteries and possess a multiporous and biocompatible surface to achieve satisfactory endothelialization in vitro. Heparin-bonded P(LLA-CL) scaffolds with autologous EC pre-endothelialization have the potential to be substitutes for natural small-diameter vessels in planned vascular bypass surgery.

Decellularized human placenta chorion matrix as a favorable source of small-diameter vascular grafts

“…2000 mmHg) calculated for the vascular grafts after decellularization but before recellularization, were in an acceptable range for in vivo situations. In contrast to our decellularized graft, other tissue engineered constructs require a long maturation time to reach appropriate burst strength [40][41][42]. For instance, in a study of L'Heureux et al in which tissue engineered blood vessels are constructed by vascular smooth muscle cells, an incubation/cultivation time of 7 weeks is needed to reach burst strength values comparable to our readily usable decellularized grafts [43].…”

Vessel Bioengineering

“…The electrospinning technique, which enables the production of nanofiber-based scaffolds, has been proposed as a promising method of fabricating arterial scaffolds (Figure 2) because of its attributions of improved cellular infiltration and endothelialization over standard synthetic grafts. 17 Electrospun smalldiameter scaffolds using biodegradable polymers, including PCL 18 and PLCL, 19 have shown good surgical and mechanical properties with a high patency rate in an arterial implantation model. Furthermore, electrospun nanofibers possess the potential of encapsulation and controlled release of drugs, 19,20 which may enable a cell-free TEVG.…”

In vitro and in vivo hemocompatibility evaluation of a new dermatan sulfate-modified PET patch for vascular repair surgery

“…Differences when using untreated PET or DS‐modified PET could be explained by the presence of DS, which could be able to prevent thrombosis, to allow the formation of the matrix and presents minor foreign body reactions that confirmed previous PET‐DS implantation studies, PET‐DS integration in vessel wall is clearly visible under polarized light and histological studies have shown the production of collagen fibers. These results are encouraging since most of the models usually described in literature used antithrombotic agents as pretreatment …”