The development of advanced biomaterials is a crucial step to enhance the efficacy of tissue engineering strategies for treatment of myocardial infarction. Specific characteristics of biomaterials including electrical conductivity, mechanical robustness and structural integrity need to be tuned to promote the functionalities of cardiac cells. In the Nikkhah lab, they have developed a new class of biomaterial scaffolding comprised of electrically conductive gold nanorods (GNRs) incorporated with photocrosslinkable gelatin-based hydrogel (GelMA) for engineering cardiac tissues with synchronous functionalities. GNRs bridge the electrically insulated matrix of gelatin hydrogel, which leads to enhanced propagation of electrical signal within the cardiac patch and consequently promotes the electromechanical cell-cell coupling.
Injectable biomaterials offer a minimally-invasive approach to deliver cells into the myocardial infarct region to maintain a high level of cell retention and viability, and initiate the regeneration process. In the Nikkhah lab in conjunction with Dr. Vernon’s lab, they have developed a biohybrid temperature-responsive poly(N-isopropylacrylamide) PNIPAAm–Gelatin-based injectable hydrogel with excellent bioactivity as well as mechanical robustness for cardiac tissue engineering. They have also incorporated QK, a VEGF-mimetic peptide, to the PNIPAAm-Gelatin backbone to promote vasculogenesis within the infarcted myocardium. The results from both labs demonstrated that PNIPAAm-Gelatin-QK hybrid hydrogel provided an excellent microenvironment to enhance the retention and viability of cardiac cells along with promoting vasculogenesis and regeneration of the injured myocardium.
Disease Modeling On-a Chip and Tumor Microenvironment Models
Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and adapt to a plethora of biochemical and biophysical signals from stromal cells and extracellular matrix (ECM) proteins. In the Nikkhah lab, they have been developing a robust in vitro three-dimensional (3D) models to study the interactions between tumor and stroma. The lab uses two approaches by developing a high-density tumor array for high-throughput screening and a microfluidic platform for precise control of the tumor microenvironment. The high-density tumor array in our lab was used to investigate the effect of matrix stiffness on different cancer cell lines (MDA-MB-231, MCF-7, MCF10a). In addition, they incorporated cancer-associated fibroblasts (CAFs) to study their effect on breast cancer dispersion. Most importantly within this model, ECM remodeling was assessed using confocal imaging and atomic force microscopy (AFM) in the absence and presence of CAFs.