'This Phase II SBIR application seeks support to continue development of a resorbable, extracellular matrix (ECM) bioscaffold derived from the urinary bladder submucosa (UBS) for tissue engineering applications in the head and neck. The three specific aims of our Phase I study were successfully completed. Specifially1 we showed that: (1) we could produce a multilaminate form of the UBS-ECM which possessed the appropriate mechanical properties for head and neck scaffold applications; (2) that the prototype UBS-ECM scaffolds retained the ability to support human microvascular endothelial cell (HMEC) adherence after all necessary material processing steps were completed; and (3) showed that the multilaminate UBS-ECM scaffold retained its function as a constructive scaffold for vocal cord reconstruction in a pilot dog study. The UBS-ECM scaffold represents an acellular, biodegradable material which supports tissue specific wound repair and provides a favorable environment for cell attachment, migration, proliferation, and differentiation. ACell, Inc. conducted the Phase I studies to determine the feasibility of producing this bioscaffold as a commercially available product for a clinical surgical applications (head and neck repair) in which there are currently limited options. The surgical repair/reconstruction of head and neck structures such as the palate, tongue, nose and orbit, larynx, pharynx, and facial skin structures presently involves the use of complicated autograft procedures, mechanical devices, or plastic surgery procedures in which there are very few options for successful reconstruction. This Phase II application proposes three specific aims which would further develop this promising scaffold. First, we will utilize the manufacturing methods established in Phase I studies to manufacture UBS scaffolds for ISO-9000 test assays required for FDA submission. Second, we will determine the fate of this resorbable UBS-ECM bioscaffold following implantation in a dog model of vocal cord reconstruction. Third, we will conduct definitive preclinical animal studies in two different species to evaluate the use of the xenogeneic, UBS-ECM scaffold for head and neck applications. These preclinical studies will involve hemilaryngectomy and laryngeal reconstruction around the UBS-ECM scaffold material. Each objective/specific aim has well defined criteria for success, and the proposed studies will be conducted by an experienced and knowledgeable research team. The 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.
Compared to body systems such as the cardiovascular system and dermatology, the need for head and neck reconstructive scaffolds is relatively small. However, there were 147,000 lingual and oral surgical cases world-wide in 1999, 85,000 pharyngeal cases, 130,000 laryngeal cases, and 2,000 eye and orbit cases. In the United States alone, head and neck surgical procedures comprise approximately 3.5% of all procedures conducted as a result of neoplasia. Clearly this is an important market with significant unmet needs.
