(3ad) Whole Organ Engineering

There is a critical shortage of donor organs with the total organ waiting list currently at 110,000 requests and the number is increasing by 5% every year; the total cost of organ failure to the US is estimated at $200B/yr. Tissue engineering offers a solution for the donor organ deficit problem by providing the tools to prepare artificial organ/tissue replacements. However, despite decades of efforts, clinical application has a single success in a relatively simple, sheet-like structure: tissue-engineered skin. The major vertical gap preventing engineering of other, more complex organs is the lack of an ideal transplantable scaffold that has all the necessary microstructure and extracellular cues for cell attachment, differentiation, function and vascularization, which has so far proven difficult to manufacture using a grounds-up approach. Recently, I developed a cadaveric organ decellularization protocol to create a whole-liver scaffold for engineering liver grafts. The decellularized organ matrix scaffold is an ideal platform for preparation of organ grafts because it represents the tissue specific extracellular matrix (ECM) composition, which aids in cell engraftment and function. The perfusion decellularized organ matrix scaffold also has the tissue specific microarchitecture that facilitates perfusion of the graft and subsequently allows delivery of nutrients and removal of waste materials from the cells that are seeded inside. The preserved vascular bed allows connection of the graft directly to the recipient’s blood torrent upon transplantation, making it surgically ideal. My research trajectory focuses on developing technologies to create tissue engineered organ grafts for transplantation using whole organ scaffolds. Reaching this goal requires parallel research in multiple intertwined projects that are cross cutting across tissue engineering, developmental biology, and surgical research. Therefore, my objective as an independent research faculty is to create an interdisciplinary, collaborative Engineering in Regenerative Medicine program that incorporates expertise of engineers, scientists and surgeons where the main research thrusts are 1) engineering of transplantable organ grafts, 2) investigation of matrix-stem cell interactions and 3) transplantation of engineered organ grafts.