Mechanically reinforced biotubes for arterial replacement and arteriovenous grafting inspired by architectural engineering

Abstract

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.

Functionalization of in vivo tissue-engineered living biotubes enhance patency and endothelization without the requirement of systemic anticoagulant administration

“…Immunofluorescence staining revealed that the lumen surface of rat-derived PBs (inner diameter: 2 mm) and canine-derived PBs (inner diameter: 3.5 mm) were covered by α-smooth muscle actin-positive (α-SMA + ) cells ( Figs. S1e and f , Supporting Information), which was in-line with our previous observations [ 51 ].…”

“…Subcutaneous implantation of our previously optimized melt spun PCL fiber skeleton [ 51 ] was re-employed in this study to generate PBs. Firstly, the optimized melt-spin preparation parameters were followed, and the resultant PCL fiber skeletons were morphologically characterized ( Table S1 and Figs.…”

“…In vivo tissue engineering exploits the foreign body response (FBR) to implanted materials and can be used to fabricate autologous TEVGs [ 49 , 50 ]. Previously, we fabricated polymer-reinforced biotubes (PBs) by subcutaneous implantation (SI) of melt-spun poly(ε-caprolactone) (PCL) fiber skeletons [ 51 ]. PBs circumvented issues relating to insufficient mechanical strength that is typically encountered by traditional biotubes consisting only of autologous tissue [ 52 ].…”

“…PBs circumvented issues relating to insufficient mechanical strength that is typically encountered by traditional biotubes consisting only of autologous tissue [ 52 ]. Our PBs excelled in their demonstratable biomechanical, biodegradable and vascular regeneration properties, but their implantation in canine arterial replacement models required oral anticoagulant drugs to be administered throughout the implantation period to maintain patency [ 51 ]. Therefore, we hypothesise that modifying PBs to improve hemocompatibility can eliminate the need for administration of anticoagulant drugs in large animal models.…”

Prosthetic vascular grafts engineered to combat calcification: Progress and future directions

“…This demonstrated that using macro‐porous vascular grafts improved the regeneration of the neo‐vessel which mirror the structure and function of the native arteries. More recently, Zhi et al (2022) created PCL‐based vascular grafts inspired by architectural engineering. Specifically modeled after architectural design of steel fiber reinforcement of concrete for tunnel construction, PCL fiber skeletons were fabricated by melt‐spinning and heat treatment before subcutaneous embedding for the deposition of cells and ECM.…”