(511f) Development of Scaffolds with Deterministic Microstructure for the Guidance of Tissue Growth In Vitro and In Vivo

An outstanding challenge in the field of regenerative medicine is the growth of microphysiological structure within macroscopic, target tissues.  In our labs, we are investigating the use of microstructure with 3-D scaffolds to stimulate and direct the formation of appropriate physiology.  In this talk, I will discuss the challenges and opportunities presented by the fusion of microfabrication with tissue engineering approaches both in vitro and in vivo.  I will illustrate these points with the following two studies:  1) Model microvessels in vitro.  The recapitulation of microvascular structure in vitro would provide a basis for dissecting angiogenic processes in development and in clinical contexts such as wound healing and tumor vascularization.  I will present a summary of our effort to grow physiologically appropriate microvessels in the lab.  In particular, I will show that we can use microfluidic structure formed in cell-remodelable matrices to initiate the growth of vessels with appropriate physiology, permeability, and response to biochemical and mechanical stimuli.  2) Invasion of porous matrices in vivo.  Biomaterials with random porous structure are used successfully in the clinic to encourage the regrowth of the dermis in deep wounds.  Yet roles of the pores have not been elucidated and these scaffolds fail to provide fast enough invasion of the host vasculature for many applications.  I will present the development of implantable scaffolds with pores and networks of conduits of well-defined size and shape formed by microfabrication.  Based on multi-week implantation of these scaffolds in a murine (mouse) wound model, I will show that the geometry and dimension of the pores have a dramatic impact on the invasion of tissue and blood vessels.  I will discuss our insights into the cellular, chemical, and mechanical processes that dictate this process.  Finally, I will show that appropriate deterministic paths guide rapid invasion over macroscopic distances, leading to significantly higher densities of tissue and vascular structure than in random matrices.