Research Project
10298446
ABSTRACT Each year more than 3 million craniofacial injuries occur in the US as a result of trauma, combat-associated lesions, tumor removal, congenital abnormalities, and aging. Although some of these conditions can be addressed by using the patient?s own tissues grafted from another site, this approach leaves the patients susceptible to infections and creates additional trauma. Currently available methods for treatment and restoration of craniofacial defects have limitations with the availability of autografts, immune rejection, high cost, inadequate implant characteristics (oxygen content, mechanical properties, porosity, biocompatibility, degradation, infection risks), and lack of vascularization. Bone repair is crucial to restore patient functionality post-injury. Scaffolds that are easy-to-handle, inexpensive, biodegradable, bioactive, and non-immunogenic with adequate porosity and oxygen content as well as proper mechanical strength are highly sought after for repairing craniofacial defects. The choice of the implant material is of critical importance to facilitate recovery of the injured patients. Recently we developed highly porous scaffolds composed of naturally derived polymers and oxygen-generating components. When combined with cell sources that are compatible with the host, these scaffolds can enhance craniofacial tissue healing. We propose to use materials that are easily accessible, porous, tunable, degradable, and biocompatible. We aim to fabricate hybrid hydrogels that are composed of oxygen-generating depots and gelatin, characterize their physical, chemical, and biological properties as well as studying differentiation of cells and vascularization in these composites. Our preliminary findings suggest that the proposed novel composite hydrogels exhibit significantly improved mechanical properties and indicate a favorable in vivo response by subcutaneous implantation in a rat model as well as full regeneration of critical sized cranial defects. In Aim 1, we will synthesize and characterize oxygen-generating biomaterials with optimized performance and characterize them. In Aim 2, we will assess how the oxygen-generating depots affect cell differentiation and osteogenesis, and develop a vascularized osteogenic model as well as evaluating the functionality of these constructs. In Aim 3, we will implant these composite biomaterials into critical size calvarial defects in vivo to induce bone regeneration. We expect that the integration of oxygen-generating depots into photocrosslinkable hydrogels will result in a material with improved mechanical properties and will promote cell growth, differentiation, biomineralization, and vascularization. These composite biomaterials will be suitable for repair or regeneration of craniomaxillofacial tissues. Because oxygen-generating scaffolds will have outstanding tunability, they are expected to be also useful for applications in other tissues such as cartilage. Porous scaffolds with high oxygen content are highly promising materials for creating functional vascularized tissues, and are expected to improve craniomaxillofacial tissue repair and human health.
