Stephen E. Feinberg, DDS, MS, PhD
Professor of Surgery
Associate Chair & Director of Research
University of Michigan Health System
B1-208D Taubman Center Box 0018
1500 East Medical Center Drive
Ann Arbor, MI 48109
Our research activities are focused on advancing regenerative medicine and somatic stem cell therapy through the development and commercialization of innovative products by combining advanced cell technology and advanced biomaterials.
I. The ex vivo development of a human full-thickness oral mucosal tissue, ex vivo produced oral mucosa equivalent (EVPOME), that is suitable for intraoral grafting procedures
Our long-term goal is to produce a "smart" transduced oral mucosal graft that will be used for reconstruction of major oral defects secondary to oncologic resection, traumatic events or developmental disturbances. The graft would act both as a material for reconstruction and as a repository for in situ transmucosal delivery of recombinant growth factors or cytokines. We realize construction of ex vivo produced oral mucosa equivalents (EVPOME) is limited by amount of tissue harvested and time necessary to proliferate, seed and maturate keratinocytes on dermal equivalents. Our success with unfractionated/unsorted cultured adult human oral mucosal cells provides compelling empiric evidence that a subpopulation exists within our cell population that represents the "stem" cell compartment. In order for our technology/gene therapy to become a viable clinical alternative we need to isolate a progenitor/stem cell population. Thus, we are presently establishing expanded cultures of an enriched population of oral mucosa progenitor/stem cells, using only physical and pharmacological means, under chemically defined conditions consistent with FDA guidelines that will be the foundation for our advances into cell replacement therapy
II. The use of our platform technology for ex vivo production of oral mucosa equivalent (EVPOME) as a novel approach for the treatment of burn injuries
Oral keratinocytes that make up EVPOME grafts have several unique characteristics that may offer advantages over epidermal (skin) keratinocytes. Oral keratinocytes have a higher proliferation rate and a lower rate of terminal differentiation than epidermal keratinocytes. For this reason, relatively small donor sites can provide sufficient cell mass via ex vivo expansion to cover much larger wounds. Oral keratinocytes also secrete pro-angiogenic factors, such as VEGF and IL8, which enhance their rapid integration at graft sites. The rapid integration of EVPOME grafts may reduce infection rates and pain. We are presently developing techniques to isolate a progenitor/stem cell population from oral mucosa that will enable us to make more robust "smart" grafts with fewer cells in a shorter period of time under the auspices of our funded NIH grant.
III. Development of Non-Invasive Methods or "Tools" for the Assessment of Tissue Engineered Human Oral Mucosa
We propose to (1) develop and test three non-invasive "Tools" to assess the in vitro viability, structure, and metabolic activity of an engineered tissue in real time and (2) a fourth to assess its viability after grafting in situ. As our model system we will use an engineered tissue, Ex Vivo Produced Oral Mucosal Equivalent (EVPOME), a tissue engineered human oral mucosa developed for intraoral grafting procedures. The EVPOME has been successfully tested in a Phase I human clinical trial and offers a unique engineered tissue model, that can be followed both during its manufacturing (mfg.) process in vitro and is also physically accessible within the oral cavity after it's grafting, in situ, to small novel optical probes we will be developing.
IV. Development of 3-dimensional biomimetic scaffolds for tissue engineering of bone and/or cartilage for reconstruction of the temporomandibular joint (TMJ) and other craniofacial structures such as the mandible
Our interdisciplinary bioengineering partnership is developing an image-based approach for designing and manufacturing patient site-specific biomaterial scaffolds with specific internal architecture using an image-based engineering design method combined with a solid free-form fabrication manufacturing approach. Our focus is on the area of internal architecture of the scaffold, i.e. pore size, direction of interconnective channels and trabecular orientation, to optimize resistance to mechanical forces, encourage cell migration and nutrient diffusion and direct cell function through biologic cues or signals. We have a particular interest in development of biomimetic scaffolds that assist in the development of a prosthesis to reconstruct the condyle-ramus unit for use in reconstruction of the temporomandibular joint and the mandible.