Anchorage: Dependent Persistent Alignment of Perfused Microvasculature in Implanted Tissue Constructs

One of the challenges in engineering complex artificial tissue constructs, with defined matrix and cellular architecture, is the formation of a viable microcirculation within them, that inosculates with the host vasculature and matures into a functional microvascular bed. Current methods based on complex cell patterning in 2-D or 3-D matrix systems rely on ‘printing’ cells or patterns of cells on/ in a substrate, direct culture on patterned substrates, or endothelialization of decellularized vessels. We are now beginning to understand the effects of the microenvironment on microvascular constructs. Flow induced remodeling and maturation of angiogenic microvasculature and changes in functional characteristics when co-implanted with astrocyte precursors strongly suggests a role for the local environment in determining characteristics of the microvascular bed [1, 2]. Chang et al. have shown that neovascular networks from microvessels pre-aligned by direct-bioprinting in a collagen matrix, retain alignment when cultured in vitro, but lose alignment on implantation in vivo [3]. Though unloading of mechanically loaded tissue influences cell behavior [4], it does not explain this loss of orientation after implantation, of previously unloaded constructs. Implanted constructs have an additional level of complexity in the form of network revision and maturation with blood flow. We hypothesize that the local mechanical microenvironment, in addition to flow, dictates network morphology in vivo. This study compares the changes in pre-aligned microvascular networks implanted with and without anchorage.