EpiBone is a company engineering living, anatomically precise and functionally mature bone grafts from autologous stem cells derived from fat aspirates. Each year in the United States alone, over 900,000 bone reconstruction procedures are performed. Facial fractures affecting the nasal area, zygoma- maxillary complex, orbital area and mandible represent more than 70% of all fractured facial bones and ~20% of facial fractures are complex and involving more than one bone. Craniomaxillofacial (CMF) reconstruction is a significant challenge due to the complex bone geometries and the need to restore both the aesthetics and function for large defects. Our goal is to produce bone tissue substitutes capable of significantly improving the current standards for bone replacement and reconstruction. Our product, EpiBone-CMF, is a tissue engineered, patient-specific, living engineered bone generated from autologous adipose-derived mesenchymal stem cells (ADSCs) cultured in a bioreactor system. In past research, we have established a technology for engineering anatomically shaped living bone grafts using our proprietary bioreactor, stem cells and decellularized bone scaffolds. We showed excellent bone healing in a porcine model of craniofacial repair with grafts conditioned for 3 weeks in vitro. We now propose to build on our previous experience to establish our technology's feasibility for repairing one of the most frequently needed bones in the head and face: the zygomatic arch. Our goal is to evaluate EpiBone graft safety (host response) and efficacy (functional integration and bone remodeling) over 12 months implantation in a zygomatic arch model in pigs. The graft will be produced by infusing stem cells, isolated from a sample of the patient's fat tissue and expanded in culture, into decellularized bone scaffolds. A key component of the production process is our bioreactor, which will be used for cell seeding and conditioning. We propose that the duration of the osteogenic induction inside the bioreactor plays a fundamental role in determining the quality of the final product. We thus plan on comparing treatment of pigs divided in experimental groups for which grafts will be subjected to 1, 3 and 5 weeks of osteogenic induction prior to implantation, and comparing to scaffold controls (no cells) and no treatment. Optimization of the timing of osteogenic induction in our bioreactor will lead to improved performance of our product, and give more insights to its mechanism of action and downstream, long-term effects. The evaluation of EpiBone graft toxicology, clinical pathology and pharmacology proposed here is key to providing the safety and efficacy assessments that are requisite for our product to become a candidate for Phase I Clinical Trials in humans. Successful completion of the proposed research will bring our product closer to its clinical application, which has the potentia to revolutionize the current approach to bone repair.
Over 100,000 US patients per year suffer complex cranio-maxillofacial (CMF) fractures for which reconstruction is a significant challenge due to the complex bone geometries and the need to restore both the aesthetics and function. In this SBIR Phase II proposal, EpiBone proposes to evaluate their unique class of anatomically precise living bone grafts which are prepared by infusing autologous adipose-derived mesenchymal stem cells (ADSCs) into bone scaffolds cultured in a bioreactor system. We propose to build on our previous experience to establish our technology's feasibility for repairing one of the most frequently needed bones in the head and face: the zygomatic arch (cheek bone). Our goal is to evaluate EpiBone graft safety (host response) and efficacy (functional integration and bone remodeling) over 12 months implantation in a zygomatic arch model in pigs. The outcomes of this study will be the starting point for human studies of anatomically shaped bone grafts, and, if successful, will lead to a new class of therapies with better tissue integration, reduction in follw-up surgeries, and improved patient comfort.