PROJECT SUMMARY/ABSTRACT Over 50% of US adults over the age of 45 have missing teeth. Following tooth loss, the alveolar portion of the jaw will atrophy in a process known as residual ridge resorption. While dental implant-supported crowns have become the standard of care, market research indicates that 70% of patients must undergo a ridge augmentation procedure to provide adequate bony structure to accept implant placement. The market for bone grafts is highly fragmented, indicating that the ideal material meeting user needs does not exist. Most dentists remain dissatisfied with existing bone grafts due to their challenging handling properties and poor predictability. Due to the lack of structural integrity, they typically require extra costs and steps to place ancillary containment devices to prevent graft migration and fibrous tissue ingrowth that impedes bone regeneration. As a result, a secondary augmentation procedure is required in 30% of cases to ensure sufficient volume for implant placement. RevBio, Inc. has developed a highly porous, regenerative bone graft biomaterial with adhesive properties called Tetranite® Adhesive Dental Bone Scaffold (TN-ADBS). Unlike currently available graft materials, TN-ADBS is cohesive during application and its unique adhesive properties allow it to maintain form, eliminating the need for ancillary fixation or containment devices. TN-ADBS is comprised of O-Phospho-L-Serine (OPLS), which in part makes it uniquely adhesive to bone and studies have also found OPLS during its resorption and local release to be osteopromotive, lending this product to yield a more predictable and efficacious product. Prior funding from the NIH-Michigan Pittsburgh Wyss Regenerative Medicine Resource Center has been used to: (a) develop TN-ADBS, (b) evaluate its performance in user handling trials, (c) develop a canine model with a mandibular critical-sized defect, and (d) conduct preliminary efficacy studies in this model. Based on FDA feedback, TN-ADBS will be regulated as a device-led combination product, where OPLS is the drug constituent promoting bone regeneration. The following proposed Phase II grant application is designed per recent FDA feedback to address the following two Specific Aims: (1) to assess the local/systemic effects of TN-ADBS (OPLS) and pharmacokinetics/pharmacodynamics (PK/PD) under maximal use conditions in a New Zealand white rabbit model and (2) to demonstrate the safety and efficacy of TN-ADBS in a pivotal animal study for the intended clinical use to augment deficient jaw bone by (i) showing local or systemic adverse effects of TN-ADBS treated defects are non-inferior to controls and (ii) by showing superior ridge height maintenance throughout the course of bone substitution in comparison to controls (p<0.05). The results from these translational animal studies, complementary to surgeon-validated simulated use trials and biological safety evaluation studies, will be used as the basis for filing an Investigational Device Exemption (IDE) with the FDA to initiate human studies. Long-term, RevBio’s mission is to provide surgeons with a novel bone grafting product to simplify surgery and improve clinical outcomes for dental ridge augmentation.

PROJECT NARRATIVE At least 50% of US adults over the age of 45 have missing teeth; however, over 70% of patients must first undergo a ridge augmentation procedure to provide adequate bony structure to accept implant placement. Most dentists remain dissatisfied with existing bone grafts due to their challenging handling properties and poor predictability that often require a secondary augmentation procedure. The proposed project aims to demonstrate through translational animal testing how a novel regenerative bone adhesive scaffold can accelerate volume preserving bone regeneration in patients seeking treatment with residual ridge resorption.