Abstract

Microvasculature-on-a-chip for Tissue Engineering and Precision Medicine

Rong Fan, Harold Hodgkinson Professor of Biomedical Engineering, Yale University

One of the major challenges in tissue engineering for transplantation and regenerative medicine is revascularization. Due to the complexity of angiogenesis and vasculogenesis mediated by a host of cellular and soluble mediators, it remains a daunting challenge to recapitulate the perivascular microenvironment in vitro for effective neotissue vascularization prior to transplantation. Stromal cells, such as fibroblasts and pericytes, provide not only mechanical support but also paracrine signals to regulate vascular morphogenesis and function. We are working to develop integrative microsystems that combine various stromal cell components and soluble signals derived therefrom to engineer high quality microvasculature network in vitro with the ultimate goal to achieve revascularization of large-sized neotissues and thus improve the performance post transplantation. First, we are harnessing the paracrine signals from phenotypically modified stromal cells (e.g., fibroblasts) to create endothelialized microvessel network in native extracellular matrix (e.g., collagen, fibrin, etc) hydrogels. Second, we are applying this platform to revascularization of mouse pancreatic islets in vitro, which can accelerate functional anastomosis with host tissue after implantation. The vascularized islets are characterized for glucose sensing and insulin production in response to glucose. Third, leveraging the success of in vitro tissue revascularization to build a brain tumor perivascular niche (PVN)-on-a-chip model to investigate the dynamics of glioma stem/progenitor cells in PVN and their resistance or response to treatment.  All together, these are to address a critical need in tissue engineering and open new opportunities for in vitro modeling of tumor microenvironment for precision medicine.