Replacement of diseased tissue requires that the implanted material not only have the proper mechanical strength, but it must also have a functioning blood distribution network (vasculature; veins, capillaries), and these are often difficult to manufacture. This project will seek to understand and mimic the structure and vasculature of three-dimensional (3D) cardiac tissue. The goal is to engineer a mechanically strong and functional cell patch for the regeneration of damaged heart tissue.
The proposed research will also provide opportunities for undergraduate and graduate students, as well as underrepresented community college students, to be involved in interdisciplinary stem cell and tissue engineering research. In addition, a series of seminars will be hosted to increase stem cell and tissue engineering awareness among the health community and public in the UP (Upper Peninsula) of Michigan.
The overall objective of the project is to create aligned nanofibrous natural extracellular matrix (ECM) scaffolds for the biofabrication of a prevascularized anisotropic stem cell patch and elucidate the mechanism of microvessel orientation within the in vivo microenvironment. Human mesenchymal stem cells (hMSCs) are immunoregulatory, regenerative, effective in promoting myocardial regeneration, and function as pericytes to stabilize the microvessels formed by endothelial cells (ECs). These unique properties enable hMSCs to combine with ECM scaffolds and ECs to biofabricate an off-the-shelf or patient-specific prevascularized patch, in which hMSCs will play a dual role of stabilizing vasculature formed by ECs in vitro and orchestrating the regeneration of dead cardiac tissue after implantation. In this project, hMSCs will be co-cultured with ECs in a nanofibrous ECM scaffold to form an aligned capillary-like vasculature, and the effects of aligned nanofibers on the density, orientation and maturation of the microvessels will be investigated. The prevascularized hMSC sheets will be multi-layered and further matured in a perfusion bioreactor, and the role of physiological interstitial flow on the inter-connections, alignment and maturation of the existing microvessels within the 3D biomimetic tissue platform will be evaluated. If successful, this project could lead to the development of personalized or off-the-shelf cardiac tissue patches that could dramatically increase the success rate for the treatment of dead cardiac muscle associated with heart attacks.