This Phase I SBIR application seeks support to develop and evaluate a mu1tilaminate sheet form of an extracellular matrix (ECM) bioscaffold for tissue engineering applications in the head and neck. Porcine-derived ECM harvested from the urinary bladder submucosa (UBS) represents an acellular biodegradable scaffold material which supports cell attachment, migration, proliferation and differentiation, and wound healing. Processed single sheets of UBS and other ECMs have shown excellent tissue remodeling capabilities in preclinical animal studies and early human clinical studies. With SBIR Phase I support, we propose to develop a multilaminate sheet form of UBS and evaluate its ability to support in vitro cell adherence and in vivo tissue repair using a dog model of head and neck reconstruction. There are three specific aims. First, we will determine the manufacturing specifications for a prototype multilaminate UBS device with defined mechanical properties. Secondly, we will evaluate the ability of the multilaminate UBS device to support human microvascular endothelial cell adherence. The third specific aim will evaluate the utility of the multilaminate UBS construct in a dog pilot study in which vocal cords are excised and replaced by the UBS scaffold. Currently, there are limited options for the surgical repair/reconstruction of head and neck structures such as the palate, tongue, nose and orbit, larynx, pharynx, and facial skin structures. Successful completion of the three specific aims is the next logical step in the development of a biodegradable scaffold which augments wound repair and promotes restoration of more normal structure and function that is currently possible with existing biomaterials and surgical techniques. Each objective/specific aim has well-defined criteria for success, and the proposed studies will be conducted by an experienced and knowledgeable research team. A time line for the proposed work is provided and the technology involves an innovative tissue engineering approach in a medical field with significant unmet needs.
The use of UBS-ECM for the tissue engineering applications of head and neck reconstruction is in some ways an orphan market. Most biomaterials are developed primarily for other applications with head and neck receiving secondary considerations. In the United States alone, the head and neck region comprises approximately 3.5% of all cancers. There are more than 400,000 cases of head and neck cancer worldwide each year, and this list does not include any of the congenital or traumatic abnormalities of the head and neck.
