(25a) Invited Talk: Synthetic Fiber-Hydrogel Composites for Cardiovascular Tissue Engineering

A grand challenge in the field of cardiovascular tissue engineering is the production of functional, vascularized myocardial tissue for treating congenital heart defects or injury arising from myocardial infarct. Central to addressing this challenge is the design of the scaffolding in which cells are organized and delivered, which also critically defines a variety of microenvironmental cues governing cell biology and resulting function. For engineering cardiac tissue, naturally derived matrices such as hydrogels composed of collagen or fibrin have been the most explored given their ease of use and the ability for cells to physically and enzymatically remodel these materials. However, these natural matrices are difficult to tune (often essential to optimizing the biologic of incorporated parenchymal cells in an engineered tissue graft) and typically rapidly resorb following implantation, rendering their utility in engineering long-term organ replacement therapies limited. In contrast, synthetic or semi-synthetic biomaterials provide a means to highly tunable microenvironmental cues that can be catered to incorporated parenchymal cells and provide control over degradation mechanisms and resorption rates. However, while synthetic hydrogels enable numerous axes of microenvironmental control that can improve the function of long-term tissue grafts, this class of materials typically possess lower potential for cellular remodeling required for tissue assembly, due in large part to their amorphous microstructure and nanoscale porosity. In this talk, I’ll discuss some of the composite strategies developed in my lab to achieve the best of both classes of materials towards the overall goal of designing vascularized myocardial tissue. By integrating synthetic matrix-like fibers into natural hydrogels, we have established a means for engineering organized, contractile myobundles and capillary beds that can integrate with host vasculature upon implantation.