The goal of this Small Business Innovation Research (SBIR) project is to develop a new medical implant device that will be more effective at enhancing bone re-growth following treatment and/or removal of diseased osseous tissue than those devices and implants currently employed in bone therapy. The objective of this Phase I application is to demonstrate the feasibility of producing a novel nanocalcium sulfate/ growth factor (Ncs/Gf) bone regeneration device by characterizing, with various in- vitro and in-vivo test systems, a material developed by scientists at the University at Buffalo. The objective of a Phase II application, should Phase I be successfully completed, will be to produce an optimized Ncs/Gf device and complete the necessary preclinical efficacy and safety studies required by the FDA to initiate studies in humans. Nanocalcium sulfate (Ncs) has tremendous potential for use as a ceramic matrix, scaffold and/or vehicle to deliver growth factors for osseous regeneration in a variety of clinical situations. Calcium sulfate has been used for more than 100 years in Dentistry and medicine. In its hemihydrate form, it has been used as a bone graft material and has been demonstrated in many animal and clinical studies to be an effective osteoconductive scaffold that enhances bone regeneration. Studies from our group have shown that conventional sized calcium sulfate can adsorb platelet-derived growth factor (PDGF-BB) and support human osteoblastic cell proliferation in vitro in an enhanced manner when compared to treatment with growth factors alone. It is proposed here that Ncs will have several advantages for use as an osseous grafting material. In particular, with particles in the range of 1-100 nm, it is posited that there will be enhanced physical properties such as high surface area for growth factor adsorption with the potential for controlling the rate of release of the adsorbed material, and superior mechanical strength for optimal osteoconductivity and resistance to fractures. The Specific Aims are designed to demonstrate that optimized Ncs material will absorb more PDGF-BB than standard clinically used calcium sulfate. This material will consequently significantly enhance osteoblastic cell attachment, proliferation and differentiation in vitro and support osseous regeneration in an in vivo rat calvarial defect model in comparison to clinically available calcium sulfate and another medical implant device that employs PDGF-BB and a tricalcium phosphate matrix. The Ncs implant device to be developed here should be of great therapeutic value for many clinical procedures focused on optimal bone regeneration. Public Health Significance: Bone grafting is a widely used clinical technique in both orthopedics and Dentistry to replace and regenerate bone in osseous deficiencies caused by disease, trauma or surgical procedures. Although many forms of this therapy have been used successfully in a wide variety of osseous defects, the current forms all have limitations such as material availability, handling and placement problems, donor site morbidity, risk of inducing transmissible disease, etc. Calcium sulfate has been used for over 100 years in orthopedics and in Dentistry with such applications as osseous lesions of periodontal disease, endodontic lesions, alveolar bone loss and maxillary sinus augmentation because of its ease of handling and positive osteoconductive effects and its ability to serve as a reservoir for growth factors. The development of a nanocalcium sulfate (Ncs) with particles in the range of 1-100 nm should have enhanced physical properties for optimal osteoconductivity and resistance to fractures. The Ncs material proposed here for further development, therefore, has great potential to be developed into a product that will have many advantages over other materials presently used in bone regeneration for both systemic and oral defects and be useful for a worldwide health need.
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