There is a lack in clinically-suitable vascular grafts. Biotubes, prepared using in vivo tissue engineering, show potential for vascular regeneration. However, their mechanical strength is typically poor. Inspired by architectural design of steel fiber reinforcement of concrete for tunnel construction, poly(ε-caprolactone) (PCL) fiber skeletons (PSs) were fabricated by melt-spinning and heat treatment. The PSs were subcutaneously embedded to induce the assembly of host cells and extracellular matrix to obtain PS-reinforced biotubes (PBs). Heat-treated medium-fiber-angle PB (hMPB) demonstrated superior performance when evaluated by in vitro mechanical testing and following implantation in rat abdominal artery replacement models. hMPBs were further evaluated in canine peripheral arterial replacement and sheep arteriovenous graft models. Overall, hMPB demonstrated appropriate mechanics, puncture resistance, rapid hemostasis, vascular regeneration, and long-term patency, without incidence of luminal expansion or intimal hyperplasia. These optimized hMPB properties show promise as an alternatives to autologous vessels in clinical applications.

Long-term results of implants in small animal models can be used to optimize the design of grafts to further promote tissue regeneration. In previous study, we fabricated a poly(ɛ-caprolactone) (PCL) bi-layered vascular graft consisting of an internal layer with circumferentially aligned microfibers and an external layer with random nanofibers. The circumferentially oriented vascular smooth muscle cells (VSMCs) were successfully regenerated after the grafts were implanted in rat abdominal aorta for 3 months. Here we investigated the long-term (18 months) performance of the bi-layered grafts in the same model. All the grafts were patent. No thrombosis, aneurysm, or stenosis occurred. The endothelium maintained complete. However, most of circumferentially oriented VSMCs migrated to luminal surface of the grafts to form a neointima with uniform thickness. Accordingly, extracellular matrix including collagen, elastin, and glycosaminoglycan displayed high density in neointima layer while with low density in the grafts wall because of the incomplete degradation of PCL. A small amounts of calcification occurred in the grafts. The contraction and relaxation function of regenerated neoartery almost disappeared. These data indicated that based on the structure design, many other factors of grafts should be considered to achieve the regenerated neoartery similar to the native vessels after long-term implantation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2596-2604, 2018.

Electrospun polymer scaffolds are regarded as an ideal tissue engineering scaffold due to similar morphological properties with the native extracellular matrix. Among these, polycaprolactone is widely used to fabricate electrospun fibrous scaffolds due to its excellent biocompatibility, good mechanical properties, and ease of manufacture. However, its low biodegradation rate has a negative influence on its application in tissue engineering scaffold. To address this issue, this study prepared hybrid scaffolds composed of polycaprolactone and polydioxanone (a fast-degrading polyether-ester) via either the blend or co-electrospinning. Subsequently, the structural characteristics, mechanical strength, in vitro/vivo degradation, cellularization, and vascularization of two kinds of hybrid scaffolds were evaluated to decide which method is more suitable for producing tissue engineering scaffolds. The incorporation of polydioxanone increased the mechanical strength of both composite scaffolds. Moreover, co-electrospun scaffolds exhibited improved hydrophilicity compared to blend scaffolds. The results of in vitro and in vivo degradation studies showed that the degradation rate of both composite scaffolds was faster than that of neat polycaprolactone scaffolds due to the incorporated polydioxanone component. Especially in co-electrospun scaffolds, the fast degradation of polydioxanone fiber gave rise to larger pore size, thus leading to faster cellularization and better vascularization compared to blend scaffolds. Therefore, co-electrospinning was demonstrated to be superior to blend electrospinning for the preparation of composite scaffolds. Co-electrospun polycaprolactone–polydioxanone scaffolds may be promising candidates for tissue engineering.

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