R01DE032406

A novel bioengineering approach to restoring permanent periodontal inflammatory bone loss - About 80% of Americans experience periodontitis in their lifetime. Alveolar bone loss leads to loosening or loss of teeth or dental implants that disrupts the most basic daily functions, such as eating and speaking.

Various bone grafts are being used to restore alveolar bone loss, but poor prognosis remains a long-standing problem. Autografts are considered the gold standard, but these grafts exhibit significant volume loss in inflammatory conditions. The available amount of material for autografts is limited, and surgical harvesting procedures are often complex and associated with morbidity, pain, and infection at the donor site.

Allografts and xenografts have less bone formation capacity than autografts, while they are also associated with risks of infection, disease transmission, and immunological rejection by the host. Synthetic bone grafts such as hydroxyapatite (HAP) and beta-tricalcium phosphate (β-TCP) have also been widely used, mostly in granule or block form. However, none of the existing synthetic bone graft materials exhibit sufficient bone formation capacity to restore inflammatory alveolar bone loss to pre-disease levels.

There is a significant unmet medical need for the development of a next-generation bone implant that can effectively regenerate alveolar bone in chronic inflammatory conditions. Alveolar bone almost never spontaneously regenerates in the presence of chronic inflammation. Excess inflammation destroys tissues and supports the growth of pathogens, leading to the realization that effective control of microbiome dysbiosis in periodontitis cannot be achieved without effective control of inflammation.

Inflammation can be resolved by specialized pro-resolving lipid mediators (SPMs) that can rapidly restore tissue homeostasis to stop the negative feedback loop of infection-inflammation and boost bone regeneration. SPMs effectively regulate inflammation in utero through early childhood, but their production and effectiveness diminish with age. In many instances, chronic inflammatory diseases such as periodontitis are associated with a failure of natural resolution pathways.

Here, we aim to develop an innovative 3D printed customized biomimetic and immunomodulatory alveolar bone implant that can provide targeted key biological factors for inflammation modulation and bone regeneration. We will use whitlockite (WH) nanoparticles, the second most abundant bone mineral in humans with excellent bone formation capacity, to develop SPM-delivering bone-mimetic ink material for 3D printing a customized, personalized bone implant that can stably fit into alveolar bone defects to effectively resolve inflammation and boost bone regeneration.

During this research project, we will establish a novel bioengineering process for preparing this innovative alveolar bone implant that can later be used by clinicians. The therapeutic effectiveness of the SPM-delivering bone-mimetic implant will be evaluated in a periodontitis model with alveolar bone loss. We envisage that the proposed biomimetic immunomodulatory 3D printed bone implant will significantly improve alveolar bone regeneration in severe inflammatory periodontitis or peri-implantitis and lead to a breakthrough in the treatment of non-healing inflammatory skeletal defects.

Brigham & Womens Hospital

NIDCR EXTRAMURAL RESEARCH PROVIDES RESEARCH FUNDS TO SUPPORT BASIC, TRANSLATIONAL, AND CLINICAL RESEARCH IN DENTAL, ORAL, AND CRANIOFACIAL HEALTH AND DISEASE THROUGH GRANTS, COOPERATIVE AGREEMENTS, INCLUDING SMALL BUSINESS RESEARCH THROUGH THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAMS AND CONTRACTS THAT SUPPORT SCIENTISTS WORKING IN INSTITUTIONS THROUGHOUT THE UNITED STATES AND INTERNATIONALLY. EXTRAMURAL PROGRAMS PLAN, DEVELOP, AND MANAGE SCIENTIFIC PRIORITIES THROUGH PORTFOLIO ANALYSES AND CONSULTATION WITH STAKEHOLDERS, ENCOURAGING THE MOST PROMISING DISCOVERIES AND EMERGING TECHNOLOGIES FOR RAPID TRANSLATION TO CLINICAL APPLICATIONS. THE INTEGRATIVE BIOLOGY AND INFECTIOUS DISEASES PROGRAMS SUPPORT BASIC AND TRANSLATIONAL RESEARCH PROGRAMS ON ORAL MICROBIOLOGY; SALIVARY BIOLOGY AND IMMUNOLOGY; ORAL AND SALIVARY GLAND CANCERS; NEUROSCIENCE OF OROFACIAL PAIN AND TEMPOROMANDIBULAR DISORDERS; MINERALIZED TISSUE PHYSIOLOGY; DENTAL BIOMATERIALS; AND TISSUE ENGINEERING AND REGENERATIVE MEDICINE. THE BRANCH AIMS TO ACCELERATE PROGRESS IN BASIC AND TRANSLATIONAL RESEARCH IN THESE AREAS, AND FURTHER STIMULATE THE DISCOVERY PIPELINE BASED ON CLINICAL NEEDS. THE TRANSLATIONAL GENOMICS RESEARCH PROGRAMS SUPPORT BASIC AND TRANSLATIONAL RESEARCH IN GENETICS, GENOMICS, DEVELOPMENTAL BIOLOGY, AND DATA SCIENCE TOWARD THE GOAL OF IMPROVING DENTAL, ORAL, AND CRANIOFACIAL HEALTH. THE FOCUS IS ON DECIPHERING THE GENETIC, MOLECULAR, AND CELLULAR MECHANISMS UNDERLYING DENTAL, ORAL, AND CRANIOFACIAL DEVELOPMENT AND ANOMALIES. THE BEHAVIORAL AND SOCIAL SCIENCES RESEARCH PROGRAMS SUPPORT BASIC AND APPLIED RESEARCH TO PROMOTE ORAL HEALTH, TO PREVENT ORAL DISEASES AND RELATED DISABILITIES, AND TO IMPROVE MANAGEMENT OF CRANIOFACIAL CONDITIONS, DISORDERS, AND INJURY. THE PROGRAM PRIORITIZES MECHANISTIC RESEARCH THAT CONTRIBUTES TO A CUMULATIVE SCIENCE OF BEHAVIOR CHANGE, TO MAXIMIZE THE RIGOR, RELEVANCE, AND DISSEMINATION OF EFFICACIOUS BEHAVIOR CHANGE INTERVENTIONS. THE CLINICAL RESEARCH PROGRAMS SUPPORTS PATIENT-ORIENTED, POPULATION, AND COMMUNITY BASED RESEARCH AIMED AT IMPROVING THE DENTAL, ORAL, AND CRANIOFACIAL HEALTH OF THE NATION. THE CENTER FOCUSES ON A VARIETY OF DISEASES AND CONDITIONS THROUGH CLINICAL TRIALS, EPIDEMIOLOGIC STUDIES, PRACTICE-BASED RESEARCH, THE HIV/AIDS AND ORAL HEALTH PROGRAM, AND STUDIES OF ORAL HEALTH DISPARITIES AND INEQUITIES IN ALL AREAS OF NIDCR PROGRAMMATIC INTEREST. THE PROGRAM ENCOURAGES INVESTIGATIONS THAT HAVE THE POTENTIAL TO TRANSLATE FINDINGS INTO EVIDENCE-BASED CLINICAL APPLICATIONS. THE RESEARCH TRAINING AND CAREER DEVELOPMENT EXTRAMURAL PROGRAMS SPAN THE CAREER STAGES OF SCIENTISTS, SUPPORTING RESEARCH TRAINING AND CAREER DEVELOPMENT FOR PHD AND DUAL DEGREE DDS/DMD-PHD STUDENTS, POSTDOCTORAL SCHOLARS AND EARLY CAREER, MIDCAREER, AND ESTABLISHED INVESTIGATORS. THE PROGRAMS MANAGE SUPPORT FOR FELLOWSHIPS, RESEARCH TRAINING GRANTS, CAREER DEVELOPMENT AND CAREER TRANSITION AWARDS, NIH LOAN REPAYMENT AWARDS, AND DIVERSITY SUPPLEMENTS TO SUPPORT RESEARCH EXPERIENCES FOR HIGH SCHOOL STUDENTS THROUGH INVESTIGATORS. EXTRAMURAL PROGRAMS ARE ACCOUNTABLE FOR THE EFFICIENT AND EFFECTIVE USE OF TAXPAYER FUNDS TO SUPPORT RESEARCH ON DENTAL, ORAL, AND CRANIOFACIAL DISEASES AND DISORDERS AND IMPROVING THE ORAL HEALTH OF ALL AMERICANS. EXTRAMURAL PROGRAMS SUPPORT RESEARCH AND RESEARCH TRAINING TO ESTABLISH THE FOUNDATION FOR SCIENTIFIC DISCOVERIES THAT INCLUDE TRANSPARENT AND RIGOROUS PLANNING, PRIORITY SETTING, CONTINUOUS AND CONSISTENT REVIEWS OF PROGRESS, AND FOCUS ON THE DEVELOPMENT OF A DIVERSE, HIGHLY SKILLED, AND NIMBLE WORKFORCE THAT CAN RAPIDLY RESPOND TO SCIENTIFIC BREAKTHROUGHS AND PUBLIC HEALTH CHALLENGES. EXTRAMURAL PROGRAMS EMPLOY EVALUATION DOMAINS, FROM NEEDS ASSESSMENT AND STRATEGIC PLANNING TO IMPLEMENTATION AND PROCESS EVALUATION, PERFORMANCE MEASUREMENT, AND OUTCOMES AND IMPACT ANALYSIS TO EVALUATE STRATEGIC OBJECTIVES.

93.121 - Oral Diseases and Disorders Research

National Institute of Dental and Craniofacial Research (NIDCR) [HHS - NIH]

Boston, Massachusetts 021156110 United States

Single Zip Code

Bioengineering Research Grants (BRG) (R01 Clinical Trial Not Allowed) (PAR-22-242)

Amendment Since initial award the total obligations have increased 291% from $834,068 to $3,260,752.