Implanted Cell-Dense Prevascularized Tissues Develop Functional Vasculature that Supports Reoxygenation Following Thrombosis.

Publication Type:

Journal Article


Tissue engineering. Part A (2014)


Achieving adequate vascularization within implanted engineered tissues is a significant obstacle to maintaining viability and functionality. <i>In vitro</i> prevascularization of engineered tissues has been explored as a potential solution to this challenge. The traditional paradigm of <i>in vitro</i> prevascularization is to implant an engineered tissue with a pre-formed vascular network that is perfused following anastomosis with the host circulation. We investigated the efficacy of this strategy by implanting cell-dense prevascularized tissues created via cell-mediated contraction and composed of collagen and a collagen-fibrin mixture into dorsal window chambers surgically prepared on immunocompromised mice. We found that host-implant anastomosis takes place in 2-6 days and that perfusion of vessels within the implants is subsequently restricted by thrombosis. However, by day 7, a functional vascular network composed of host and implant vessels developed. Prevascularization enhanced intra-implant pO<sub>2</sub> significantly as early as 2 days post-implantation, reaching a maximum of 55 mmHg by day 8, which was significantly greater than the maximum within cellularized control tissues (18 mmHg). By day 14, collagen tissues supported approximately 0.51 x 10<sup>9</sup> implanted and host-derived cells per mL. Our findings elucidate key features of <i>in vitro</i> prevascularization that can be used toward the design of larger and more functionally complex engineered tissues.


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