The performance of heparin modified poly(ε‐caprolactone) small diameter tissue engineering vascular graft in canine—A long‐term pilot experiment in vivo

Abstract

Long‐term in vivo observation in large animal model is critical for evaluating the potential of small diameter tissue engineering vascular graft (SDTEVG) in clinical application, but is rarely reported. In this study, a SDTEVG is fabricated by the electrospinning of poly(ε‐caprolactone) and subsequent heparin modification. SDTEVG is implanted into canine's abdominal aorta for 511 days in order to investigate its clinical feasibility. An active and robust remodeling process was characterized by a confluent endothelium, macrophage infiltrate, extracellular matrix deposition and remodeling on the explanted graft. The immunohistochemical and immunofluorescence analysis further exhibit the regeneration of endothelium and smooth muscle layer on tunica intima and tunica media, respectively. Thus, long‐term follow‐up reveals viable neovessel formation beyond graft degradation. Furthermore, the von Kossa staining exhibits no occurrence of calcification. However, although no TEVG failure or rupture happens during the follow‐up, the aneurysm is found by both Doppler ultrasonic and gross observation. Consequently, as‐prepared TEVG shows promising potential in vascular tissue engineering if it can be appropriately strengthened to prevent the occurrence of aneurysm.

Preparation and Evaluation of Core–Shell Nanofibers Electrospun from PEU and PCL Blends via a Single-Nozzle Spinneret

“…As FDA-approved biocompatible and mechanically strong biomedical materials, PCL and PEUs are widely utilized in biomedical applications. PEUs with PCL or other biodegradable aliphatic polyesters are highly desirable to co-electrospin into a class of nanosized porous scaffolds or mats for tissue engineering and regenerative medicine as well as carriers for drug-controlled delivery. ,− As previously reported by our group, the PCL-based small-diameter iTEVGs were fabricated using electrospinning followed by surface heparinization. − Although these grafts demonstrated long-term patency in rabbit carotid artery and canine abdominal aorta replacement models, nearly all later developed aneurysmal dilation mostly caused by the uncontrolled biodegradation of PCL due to mismatch in the formation of neovascular tissues. To address the aneurysm formation and the failure of grafts when used for vascular interposition and arteriovenous vascular access, one optimal choice is to combine PEU with PCL in iTEVGs using the co-electrospinning technique.…”

Endothelialization strategy of implant materials surface: The newest research in recent 5 years

“…The surface can create a good regeneration micro-environment for the migration and adhesion of cells, which is conducive to the process of endothelialization of the material. In order to improve the cytocompatibility of the material surface, the surface of vascular implant material is usually modified based on bionics methods., that is, immobilize natural or synthetic biological functional molecules on the surface of biological materials to construct natural physiological microenvironment, such as heparin, 68 fucoidan, 69 hyaluronic acid, 70 ECM protein, 71 and peptide. 72 Based on the characteristics and advantages of heparin and hyaluronic acid, many researchers have carried out a large number of related studies and have made important progress.…”

“…Heparin can be introduced into the surface of materials by EDC/NHS crosslinking reaction. 68 Negatively charged heparin can also be introduced into the surface of the material by electrostatic interaction in the form of layer-by-layer self-assembly. 77,78 However, compared with covalent modification methods, biomolecules assembled by electrostatics are often less stable, and uncontrolled molecular bursts occur in dynamic environments.…”

The Effect of Polymer Type and Fiber Orientation on the Compliance Properties of Electrospun Vascular Grafts

“…Cardiovascular diseases, which account for 32% of all fatalities worldwide, will continue to be the leading global cause of disability and death, according to experts' predictions for the future [1,2]. There is an urgent and significant need in clinics for tissue engineered small-diameter (<6 mm) blood vessel substitutes due to a lack of availability of autologous vessels and effective commercial products used for bypass surgeries, such as vascular prostheses made of polyethylene terephthalate (PET) or expanded polytetrafluoroethylene (ePTFE), which have low clinical efficacy and a high failure rate after implantation [3,4]. Tissue engineering faces a great challenge when attempting to replicate the unique design and distinctive mechanical characteristics of the vascular wall in order to fulfill the functional needs of the native tissue [5].…”