Engineering large and thick vascularized tissue constructs and its application in tissue engineering

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ICE Krakow

ICE Krakow

ul. Marii Konopnickiej 17 30-302 Kraków


Chen, Ying-chieh (National Tsing-Hua University)


Nowadays, the main approaches to engineer vascularized tissues are to develop biomaterials combining with cell-based therapy to achieve rapid vasculogenesis angiogenesis and anastomosis between engineered and host blood vessels. However, the thickness of engineered vascularized tissues in animals were still less than 1 mm, because the hydrogel becomes less permeable with increasing thickness. To overcome this challenge, a diffusion-based computational simulation was used to guide and optimize the geometry of hydrogel structures. Then, human white adipose tissue derived mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVECs) were encapsulated into prepolymer and patterned into different kinds of three-dimensional (3D) hydrogel structures by photolithography micro-patterning technique. After subcutaneous implantation into mice, the cell-laden hexagonal structures can guide vasculogenesis and accelerated angiogenesis to form uniform distributed vascular networks in the large (diameter ≈ 2cm) and thick hydrogel (> 2 mm) within 7 days in normal and diabetic mice. The use of preformed vasculature for the timely supply of nutrients and oxygen to surrounding cells may offer a solution for improving the repair of volumetric muscle loss (VML). These vascularized soft tissues were subsequently used as the vascularized flap for the repair of VML defects. After 1-month, large portions of regenerated muscle with larger muscle fibers were well distributed at the site of injury in the group with high densities of perfused vascular networks. These findings suggest that precultivation of engineered, perfused, vascularized soft tissue with well-connected networks of capillaries prior to implantation accelerated muscle fiber repair through timely supply of sufficient blood and avoided invasion by host fibroblasts. Moreover, pancreatic islet cell transplantation is still the most ideal method for the treatment of type 1 diabetes comparing to insulin injection and pancreas transplantation. Thus, mice islets were integrated into these engineered vascularized soft tissues, and the process of islet revascularization after transplant were reviewed. After 7 days, transplanted islets were anastomosed and integrated rapidly into the surrounding engineered vasculature, and thereby significantly increased the islet viability and function observed in conventional islet transplantation. In summary, we developed a novel micro-fabrication technique to generate large and thick vascularized tissue constructs at subcutaneous site and showed its improvement in islets function and muscle regeneration. This concept could serve as a platform technology for engineering various vascularized tissue for tissue engineering and regeneration.

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