Development and evaluation of in vivo tissue engineered blood vessels in a porcine model.

BACKGROUND: There's a large clinical need for novel vascular grafts. Tissue engineered blood vessels (TEBVs) have great potential to improve the outcome of vascular grafting procedures. Here, we present a novel approach to generate autologous TEBV in vivo. Polymer rods were engineered and implanted, evoking an inflammatory response that culminates in encapsulation by a fibrocellular capsule. We hypothesized that, after extrusion of the rod, the fibrocellular capsule differentiates into an adequate vascular conduit once grafted into the vasculature. METHODS AND RESULTS: Rods were implanted subcutaneously in pigs. After 4 weeks, rods with tissue capsules grown around it were harvested. Tissue capsules were grafted bilaterally as carotid artery interposition. One and 4-week patency were evaluated by angiography whereupon pigs were sacrificed. Tissue capsules before and after grafting were evaluated on tissue remodeling using immunohistochemistry, RNA profiling and mechanical testing. Rods were encapsulated by thick, well-vascularized tissue capsules, composed of circumferentially aligned fibroblasts, collagen and few leukocytes, with adequate mechanical strength. Patency was 100% after 1 week and 87.5% after 4 weeks. After grafting, tissue capsules remodeled towards a vascular phenotype. Gene profiles of TEBVs gained more similarity with carotid artery. Wall thickness and αSMA-positive area significantly increased. Interestingly, a substantial portion of (myo)fibroblasts present before grafting expressed smooth muscle cell markers. While leukocytes were hardly present anymore, the lumen was largely covered with endothelial cells. Burst pressure remained stable after grafting. CONCLUSIONS: Autologous TEBVs were created in vivo with sufficient mechanical strength enabling vascular grafting. Grafts differentiated towards a vascular phenotype upon grafting.

Tailoring the foreign body response for in situ vascular tissue engineering.

This study describes a screening platform for a guided in situ vascular tissue engineering approach. Polymer rods were developed that upon 3 weeks of subcutaneous implantation evoke a controlled inflammatory response culminating in encapsulation by a tube-shaped autologous fibrocellular tissue capsule, which can form a basis for a tissue-engineered blood vessel. Rods of co-polymer were produced using different ratios of poly(ethylene oxide terephthalate) and poly(butylene terephthalate) to create a range of physicochemical properties. In addition, a set of different physical, chemical, and biological surface modifications were tested on their ability to actively steer this tissue capsule formation using a rat model as testing platform. Tissue capsules were mainly composed of circumferentially aligned collagen and myofibroblasts. Different implant material resulted in distinct differences in tissue capsule formation. Compared to its unmodified counterparts, all surface modifications resulted in increased wall thickness, collagen, and myofibroblasts. Oxygen plasma-treated rods resulted in loose tissue arrangement, collagen, and collagen/TGF-ß-coated rods yielded thick, collagen-rich, densely packed tissue capsules, though with a random distribution of myofibroblasts. In contrast, chloroform-etched rods provided homogenous densely packed tissue capsules, completely populated by myofibroblasts. In conclusion, by varying the implant's surface characteristics, tissue capsule composition, cell distribution, and tissue arrangement could be tailored, enabling controlled guidance of the tissue response for in vivo vascular tissue engineering.