Microstructured templates for directed growth and vascularization of soft tissue in vivo

Tissue templates for reconstruction and regeneration in vivo have achieved clinical successes for homogeneous tissues in well vascularized regions. Outstanding challenges exist for applications in poorly vascularized regions and for spatially differentiated tissues. Here, we present a strategy to control the spatial patterns of cell and vascular ingrowth throughout the volume of a bioremodelable and resorbable matrix via well-defined micropores and networks of microchannels. Our presentation of this approach includes: a description of a lithographic technique to form deterministic microstructures within a matrix of native collagen; elucidation of multistep process by which microstructures drive rapid invasion and vascularization; and demonstration of long range guidance of invasion through the full thickness of patterned templates. Experiments were performed in a murine wound model. These microstructured tissue templates (MTTs) could improve outcomes in reconstructive surgery and open paths to directed regeneration of spatially heterogeneous tissues or organs.