Synbio.Ecm: designer extracellular matrices to program healthy and diseased cardiac morphogenesis
To meet medical needs worldwide, tissue engineering must move from successful pre/clinical products towards an effective process to meet Worldwide medical needs, but this is challenging since a quantitative design framework has not emerged, yet.  Synthetic biology (SYNBIO) was the solution that genetic engineers found to the same problem: “Despite tremendous individual successes in genetic engineering and biotechnology […], why is the engineering of useful synthetic biological systems still an expensive, unreliable and ad hoc research process?” asked Dr. Endy in a 2005 letter to Nature. The SYNBIO solution included: i) libraries of DNA parts with well-characterized effect on cells; ii) tools to computationally design system-level assemblies, or designer-DNA; and, iii) bottom-up engineering of cell functions using progressively more complex designer-DNA. Effectively, SYNBIO introduced a computer-aided design and manufacturing (CAD/M) platform that transformed the process of engineering cells. However, since inputs from the extracellular matrix (ECM) have largely been ignored, progress towards programmable tissue-level behavior have been more modest. 

Here, we will build on my experience with computational and experimental models in cardiac tissue engineering to develop a CAD/M framework for engineering cardiac tissues with computationally predictable properties, or designer-ECM. To characterize ECM-cell interactions, we will use traction force and super-resolution microscopy with fluorescence in-situ sequencing. To model multiscale ECM-cell interactions, we will use ordinary differential equations and subcellular element models. Finally, we will leverage ECM parts and human induced pluripotent stem cells to bioprint designer-ECM that recapitulate three phases of heart development: trabeculation, compaction, and maturation. 

With synthetic matrix biology (SYNBIO.ECM), we will develop a CAD/M-based process and a new class of products for cardiac 
tissue engineering.