SBIR-STTR Award

This Phase I SBIR application seeks support to develop and evaluate the use of an extracellular matrix (ECM) bioscaffold derived from the urinary bladder-extracellular matrix (UBM) for the repair and reconstruction of diseased esophageal tissue. Porcine-derived UBM represents an acellular biodegradable scaffold material that supports cell attachment, migration, proliferation, differentiation, and tissue remodeling. The hydrated form of single sheets of UBM and other ECMs have shown excellent remodeling capabilities in both preclinical animal studies and human clinical studies for applications unrelated to the gastrointestinal tract. We propose to conduct three studies. Study #1 will establish manufacturing methods for a multilaminate sheet of UBM that has defined mechanical properties sufficient for esophageal repair. Study #2 will evaluate the ability of a multilaminate UBM sheet to support primary esophageal epithelial cell growth in vitro. Study #3 will utilize the prototype multilaminate UBM device in a preliminary dog study in which a full circumference segmental esophageal defect will be repaired. Currently, there are no viable options for a biomaterial to replace esophageal tissue. Esophageal stricture, and lack of esophageal motility are serious limitations to existing biomaterial alternatives for this application. As location of autologous stomach or bowel account for a majority of existing surgical techniques for the repair or reconstruction of segments of the esophagus at the present time. Successful completion of the three specific aims defined for this Phase I project will provide the necessary information to decide whether or not this UBM scaffold should be evaluated further as a biomaterial for esophageal repair. Each objective/specific aim has well-defined endpoints and criteria for success. An experienced and knowledgeable research team will conduct the proposed studies and time line for the proposed work is provided. This technology provides an innovative tissue engineering approach in a medical field with significant unmet needs. PROPOSED COMMERCIAL APPLICATION: Congenital and acquired abnormalities of the esophagus present surgical challenges with extremely limited options. Morbidity associated with surgical procedures is significant. Stricture of the esophagus following either injury or replacement of damaged tissue by existing biomaterials is a significant problem. Esophageal adenocarcinoma has increased in incidence by 350% since the mid-1970's. Since this is a clinical area with virtually no biomaterial options, the successful completion of this SBIR application addresses a significant unmet clinical need.

ACell is a tissue engineering company and its core technology is based upon a porcine derived extracellular matrix (ECM) harvested from the urinary bladder (UBM) that serves as a constructive scaffold for tissue reconstruction. Successful completion of Phase I studies showed that the UBM-ECM can be configured into a tube shaped device with mechanical and material properties suitable for the repair of esophageal tissue. These studies also showed that primary canine esophageal epithelial cells could attach, proliferate and differentiate in vitro upon the UBM scaffold. Finally, a preliminary study in a dog model demonstrated the ability of the resorbable UBM scaffold to replace native esophageal tissue with host derived tissues that included an intact squamous epithelium, submucosal vascularized collagenous tissue and subjacent bundles of skeletal muscle appropriate for the resected segment of cervical esophagus. The present Phase II SBIR proposal seeks support to pursue the development of the UBM bioscaffold as a device for the repair or replacement of damaged or missing esophageal tissue; a surgical application that currently has very limited options. There are three studies described, each of which addresses a clearly defined specific aim: (1) to determine the fate and mode of degradation of the porcine derived UBM scaffold when used as an esophageal repair device in a dog model; (2) to complete ISO-9001 testing as a prerequisite to regulatory submission of an Investigational Device Exemption (DE); and (3) to examine the safety and efficacy of the UBM device in a definitive chronic study using an animal model. The work will be conducted by an experienced interdisciplinary group of investigators and will combine the expertise of ACell's professional staff, the certified laboratories of the North America Science Associates (NamSA), and a university partner. A timeline for completion of the studies, clearly defined criteria for success, and plans for subsequent Phase III work are included in this Phase II proposal. PROPOSED COMMERCIAL APPLICATION: Congenital and acquired abnormalities of the esophagus present surgical challenges with extremely limited options. Morbidity associated with surgical procedures is significant. Stricture of the esophagus following either injury or replacement of damaged tissues by existing biomaterials is a significant problem. Esophageal adenocarcinoma has increased in incidence by 350% since the mid-1970's. Since this is a clinical area withe virtually no biomaterial options, the successful completion of this SBIR application addresses a significant unmet clinical need.

Thesaurus Terms:
biomaterial development /preparation, esophagus, esophagus disorder, extracellular matrix, tissue engineering, tissue support frame, urinary bladder epithelium biodegradable product, biomaterial evaluation, esophagus motility /pressure dog