Project Summary Craniofacial trauma leads to over 10 million emergency room visits per year in the US that cause a vast socio- economic burden. Unlike small defects, large complex defects arising from traumatic avulsive injuries or pathologic lesion resection require planned reconstruction or secondary surgery to regain bony union. Yet, these defects do not spontaneously heal and are known as “critical size defects” (CSD). Attempts to induce bone formation by vascularized autologous grafts led to donor site morbidity and low harvest volume. Further, recombinant human bone morphogenic protein (rhBMP2) growth factor used with autograft often produces harmful inflammation and swelling post-surgery. Alternatively, titanium (Ti) fixation plates lend structural support to bony fragments but lack bioactivity to speed healing. Moreover, clinically available mesoporous BioglassTM, FDA-approved polymers, or composite pastes or putties lack needed strength and bioactivity for bone healing. Our goal is to bioengineer new biomaterials that target healing mechanisms for rapid defect repair. Bone healing requires rapid regeneration of dense biomineral and vascular tissue, which depends on antioxidant activity to promote cell migration and osteogenesis by mesenchymal stem cells (MSC) and angiogenesis by endothelial cells (EC). Our objective is to stimulate bone healing by (1) revealing biomaterial chemistries that target MSC and EC antioxidant activity (2) atomistically layer these biomaterials as coatings on Ti devices to enhance bone defect healing; and (3) use new nanoparticles (NPs) chemistries embedded in biopolymer scaffolds for rapid defect healing. We created silicon oxy-nitro-phosphide (SiONPx) by chemical vapor deposition as new coatings for Ti mesh and nanoparticles (SiONPx-np) in biopolymer scaffolds that release antioxidant ions (Si4+). We hypothesize that SiONPx enhances dense bone and vascular tissue healing and rapid bone repair via enhanced antioxidant activity to promote angiogenesis and osteogenesis. In Aim 1, we will study the effect of Si4+ on the promotion of these antioxidants during MSCs osteogenesis and ECs angiogenesis. In Aim 2, we will determine the effect of SiONPx coatings to stimulate antioxidant promoters to hasten the local bone healing environment. In Aim 3, we will use SiONPx-np-biopolymer scaffolds to stimulate antioxidant promoters to promote cell migration, angiogenesis, and osteogenesis into scaffold structures to hasten the healing process. Our central innovation is the development of a new class of implantable and printable materials that can accelerate healing of craniofacial bone defects. Once such materials/devices become clinically available, there is the promise that a significant advancement will have been made toward their translation in patients needing rapid healing of large bone defects or fractures. These results will have a positive impact in supporting future clinical trials of new antioxidant materials on biomedical devices that can reduce patient healing time, reduce medical care cost, and increase the quality of newly formed bone in large defects.

Project Narrative: The benefits of this research to the general public include the development of biomaterials that can be used as effective therapies in promoting faster or more improved methods of healing bone. This could potentially lead to improved healing, shortened healing times, and reduce health care costs associated with bone healing.