Dental implants are becoming an increasingly popular option vs. dentures, bridges, and other dental prosthetics due to greater patient satisfaction and better long-term outcomes. However, osseointegrated dental implants require strong, healthy bone for implantation to be successful. While success rates for osseointegrated dental implants are relatively high (~90%), a drastic increase in the number of implantation procedures is expected to occur due to the increasing popularity of the procedure with patients and clinicians, as well as demographic factors such as an increased number of aging and elderly patients that require dental prostheses. Failed dental implantations can lead to a significant cost and care burden to patients and to the healthcare system, and initial failures often mean that additional attempts at implantation in the same site are not possible. Together, these factors signal the need for a clinical tool that will increase the rate of osseointegrated dental implant success, particularly in patients who are at higher risk for failure due to the inadequate presence of high-quality bone in which to place the implant. NaturemiRI, LLC has developed a novel method of microRNA (miR) inhibition using a biologically native molecule composed of nucleic acids with a unique secondary structure, allowing it to bind and degrade or sequester mature miRs. The inhibition of binding mature miRs to their mRNA targets alters protein production in the cell. It has been established in our preliminary studies and previously published reports that miR-200a inhibits osteogenic differentiation and increases the pro-inflammatory response. Our Phase I project goal is to demonstrate that by inhibiting miR- 200a in vitro and in an animal model, we can increase rates of osteogenesis and enhance the quality of regrown bone. During Phase I, we will analyze bone hardness, mineral content, and density during osteogenic differentiation and in an artificial wound-healing model. We also intend to demonstrate that the nucleic acid based composition of our inhibition method negates the risk of systemic toxicity?a concern that exists with the use of synthetically modified oligonucleotide miR inhibition methods. Phase I success will set the stage for a larger Phase II demonstration project focused on larger-scale testing and validation of the envisioned new tool for the dental clinic?an anti-miR-200a-infused collagen sponge that could be used in tooth extraction procedures in anticipation of future osseointegrated dental implantation. Success will also establish therapeutic proof of concept for this new miR inhibition method, ultimately opening the door for an important range of additional therapeutic applications in the dental field and beyond. NaturemiRI?s experienced team of dental researchers is established and well-suited to address the scientific questions regarding the proposed application. NaturemiRI leadership also includes a small but experienced business development team that is working diligently on commercialization activities regarding the many potential applications of this technology.
Project Terms: Address; Adult; Age; Aging; aging population; Alkaline Phosphatase; alveolar bone; Alveolar ridge; Animal Model; Animals; base; Base Composition; Binding; Biological; Biotechnology; Blood; bone; Bone Development; Bone Growth; bone healing; bone quality; Bone Regeneration; Bone Transplantation; Businesses; Calvaria; care burden; care outcomes; Cell Differentiation process; Cells; Client satisfaction; Clinical; Collagen; commercialization; Complex; cost; craniofacial; Craniofacial Abnormalities; craniofacial bone; Data; Defect; Demographic Factors; density; Dental; Dental Clinics; Dental Implantation; Dental Implants; Dental Prosthesis; Dentistry; Dentures; design; Development; dimensional analysis; Disease; Enhancers; Enzymes; experience; Failure; failure Implantation; Family; Future; Genes; Genetic Transcription; Goals; Hardness; Health; health care quality; Healthcare Systems; high risk; Human; Implant; implantation; Implantation procedure; improved; In Vitro; in vivo; Incisor; Inflammation; Inflammatory Response; inhibitor/antagonist; Lead; Leadership; Liver; Lung; Market Research; Measurement; member; Messenger RNA; Methods; MicroRNAs; Minerals; Modeling; Molecular; Natural regeneration; new technology; novel; novel therapeutics; Nucleic Acids; older patient; Oligonucleotides; Oral; Osteocalcin; Osteogenesis; osteogenic; Outcome; overexpression; Patients; permanent tooth; Phase; Physiological; Plasmids; Population trends; Porifera; preservation; Procedures; Process; Production; Prosthesis; Proteins; Publishing; Quality of life; Rattus; Reporting; Research; research and development; Research Personnel; response; Risk; Rodent Model; Safety; Signal Pathway; Signal Transduction; Site; Small Business Innovation Research Grant; Small RNA; standard care; Structure; success; System; systemic toxicity; Technology; Testing; Therapeutic; Time; tool; Tooth Extraction; Tooth Socket; Toxic effect; transcription factor; Transfection; Treatment Cost; Untranslated RNA; Validation; Work; wound closure; Wound Healing;
