SBIR-STTR Award

This project evaluates the feasibility of a new multiphasic, composite bone repair material composed of calcium sulfate (CS) particulate, protected from rapid degradation by an absorbable polymer either coated on, or within, a CS matrix. Repair of bone defects often requires the use of permanent or resorbable biomaterials. These materials can comprise autogenous or allogeneic bone graft, a range of alloplastic (calcium phosphate materials, bioglass, calcium sulfate materials) materials and composite combinations of these materials. Calcium sulfate (CS) is a fully degradable material for repair of bone defects. It is one of the oldest and safest biomaterials in current use. Recent research has shown that it is biocompatible, completely degradable, osteoconductive, does not cause inflammation and evokes minimal foreign body response. It can be used in combination with other bone graft materials such as autograft, calcium phosphate, bioglass and allografts. It has strong hemostatic activity and it prevents the ingrowth of soft tissue in the defect area acting as a barrier material. It stimulates the growth of micro blood vessels and hence is angiogenic. It causes precipitation of calcium phosphate deposits as it undergoes dissolution. These precipitates stimulate and direct the formation of new bone. The principal concern and complaint by practitioners using CS is that it (dissolves) too rapidly and outpaces the formation of new bone in some applications. Poly (L Lactic acid), (PLLA) is another biomaterial used in many biomedical devices with an excellent safety record. It is biocompatible and biodegradable. Our previous studies have shown that a composite of calcium sulfate and PLLA undergoes much slower dissolution in simulated body fluid than pure CS. Calcium phosphate precipitate formed as this composite degraded (which would stimulate the formation of bone in vivo). Depending upon the ratio of CS:PLLA, the degradation rate of the composite can be controlled. The product described here represents a cement that can be formulated to dissolve at controlled rates that can be matched with bone repair for a specific surgical application. This composite would overcome the disadvantage of fast dissolution of calcium sulfate, but would still retain all of its unique properties for bone grafting. There is a ready market for a new material to fill extraction sites, enhance maxilla and mandibular bone to accept dental implants, and to speed up the osseointegration of dental implants.

Thesaurus Terms:
biodegradable product, biomaterial development /preparation, biomaterial evaluation, bone disorder, bone regeneration, calcium, lactate, musculoskeletal disorder therapy, nonhuman therapy evaluation, sulfate biomaterial interface interaction, cell growth regulation, chemical stability, osteogenesis, polymer biotechnology, histology, laboratory rabbit, morphometry

The aim of this research is to develop an improved, synthetic bone graft material for use in dentistry. The loss of teeth is often accompanied by the loss of jaw bone. Restoring this lost bone is often a prerequisite for the installation of dental implants and the maintenance of normal facial features. Calcium sulfate works quite well as a bone regeneration material. It serves not only as a defect filler, but is also biocompatible, conducts new bone growth and encourages the growth of new blood vessels. However, its fast degradation is its major shortcoming, restricting its use in bone grafting applications. Based upon a successful phase I feasibility study, this project proposes the development of a new material: a calcium sulfate/absorbable polymer composite with anti-inflammatory properties and bone growth factor delivery capability. Phase I studies have already demonstrated that calcium sulfate/ absorbable polymer composites undergo slower degradation than pure calcium sulfate and thus overcomes a significant drawback of this material as a bone regeneration product. The plan now is to develop a product that dentists can use in bone grafting procedures that will rival the bone regeneration potential seen with the use of the patients own harvested bone. The product, a composite of calcium sulfate and Poly-Aspirin that delivers a bone growth factor, PDGF, utilizes a new polymer whose in vivo bone response has been studied in several animal models. Because of its specific chemical structure, this polymer elicits an excellent cell and tissue response and has an anti-inflammatory effect of great value in the oral environment. Since an earlier version of this product has already been commercialized, this new product will be rapidly introduced to the marketplace and an improved replacement.

Public Health Relevance:
Bone grafting is an essential component of facial and dental maintenance. Recent concern about allograft bone supply makes the development of a reliable, affordable synthetic essential to this process. This project describes the development of just such a synthetic with bone regeneration capability rivaling autografts based on a simple, affordable material with a long safety history, calcium sulfate, combined with an anti-inflammatory absorbable polymer and a bone growth factor.

Thesaurus Terms:
2-(Acetyloxy)Benzoic Acid; 2-Hydroxybenzoic Acid; Abscission; Accessory Sinuses; Acetylsalicylic Acid; Allografting; Anhydrides; Animal Model; Animal Models And Related Studies; Anti-Inflammatories; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory; Antiinflammatories; Antiinflammatory Agents; Antiinflammatory Agents, Non Steroidal; Antiinflammatory Agents, Nonsteroidal; Aspergum; Aspirin; Autograft; Autologous Transplantation; Autotransplant; Bmp-7; Bmp7; Becaplermin; Benign; Biocompatible; Bioglass; Blood Vessels; Body Tissues; Bone; Bone Formation; Bone Growth; Bone Morphogenetic Proteins; Bone Regeneration; Bone Transplantation; Bone And Bones; Bones And Bone Tissue; Calcium Sulfate; Cancers; Cells; Chemical Structure; Clinical Trials, Phase I; Clinical, Transplantation, Organ; Collagen; Cultured Cells; Defect; Dental; Dental Implants; Dentistry; Dentists; Development; Dichloromethane; Early-Stage Clinical Trials; Ecotrin; Effectiveness; Empirin; Entericin; Environment; Esters; Excision; Extirpation; Extren; Fda; Face; Feasibility Studies; Filler; Food And Drug Administration; Food And Drug Administration (U.S.); Fracture; Gfac; Graft Material; Grafting Procedure; Grafting, Bone; Growth Agents; Growth Factor; Growth Factors, Proteins; Growth Substances; Harvest; Hemostatic Agents; Hemostatics; History; Human; Human, General; In Vitro; Janssen Brand Of Becaplermin; Jaw; Kinetic; Kinetics; Maintenance; Maintenances; Malignant Neoplasms; Malignant Tumor; Man (Taxonomy); Man, Modern; Marketing; Marrow; Measurin; Mesenchymal; Methane, Dichloro-; Methylene Bichloride; Methylene Chloride; Methylene Dichloride; Mother Cells; Nsaids; Nasal Sinuses; Nasal Cavity/Paranasal; Nasal Cavity/Paranasal Sinuses; Non-Steroidal Anti-Inflammatory Agents; Nonsteroidal Anti-Inflammatory Agents; Nonsteroidal Antiinflammatory Drug; Op-1; Op-1 Protein; Op1; Oral; Organ Transplantation; Organ Transplants; Organ Transplants, Including Bone Marrow For Dct; Orthopedic; Orthopedic Surgical Profession; Orthopedics; Osteogenesis; Osteogenic Protein 1; Pdgf; Paranasal Sinuses; Parodontosis; Patients; Periodontal Diseases; Periodontal Pocket; Phase; Phase 1 Clinical Trials; Phase I Clinical Trials; Phase I Study; Phosphoric Acid, Calcium Salt (2[{..}]3); Ca3(Po4)2; Platelet-Derived Growth Factor; Platelet-Derived Growth Factor Beta Chain; Platlet-Derived Growth Factor Beta Chain; Polymers; Procedures; Process; Progenitor Cells; Property; Property, Loinc Axis 2; Public Health; Rate; Recombinant Platelet Derived Growth Factor Beta Chain; Recombinants; Recording Of Previous Events; Regranex; Removal; Research; Safety; Salicylic Acid; Salicylic Acids; Sinus; Stem Cells; Sulfuric Acid, Calcium Salt (1[{..}]1); Surgical Removal; Tissues; Tooth Loss; Transplantation Surgery; Transplantation, Autologous; Transplanted Tissue; Usfda; United States Food And Drug Administration; Week; Work; Allogenic Bone Graft; Allogenic Bone Transplantation; Allograft Bone Transplant; Base; Bone; Bone Allograft; Bone Fracture; Bone Growth Factor; Bone Morphogenetic Protein 7; Bone Repair; Calcium Phosphate; Calcium Phosphate, Tribasic; Calcium Phosphate, Tricalcium Salt; Concept; Facial; Human Skeletal Growth Factor; Improved; In Vivo; Interest; Macrophage-Derived Osteoblast Growth Factor; Malignancy; Maxillofacial; Model Organism; Neoplasm/Cancer; New Growth; Nonsteroidal Anti-Inflammatory Drugs; O-Hydroxybenzoic Acid; Organ Allograft; Organ Graft; Organ Xenograft; Ortho-Hydroxybenzoic Acid; Periodontal Disorder; Periodontium Disease; Periodontium Disorder; Phase 1 Study; Phase 1 Trial; Phase I Trial; Protocol, Phase I; Public Health Medicine (Field); Recombinant Human Bone Morphogenetic Protein-2; Resection; Response; Rhbmp-2; Rhpdgf-Bb; Septic; Skeletal Growth Factor; Tricalcium Phosphate; Vascular; Vasculogenesis