Revolutionary changes in health care are on the horizon, driven by advances in technology and a remarkable convergence of knowledge spanning diverse fields of science. The oral health community must embrace personalized, precision health care in the near term, and NIDCR is committed to being at the leading edge of this development.
As we understand more about signaling pathways, molecular interactions, and novel biomarkers that underlie health and disease, the dental, oral, and craniofacial complex stands out as a unique gateway to assess risk, prevent and diagnose disease, and guide treatment. For example, the complex can be easily accessed and repeatedly sampled for caries development, periodontal disease, saliva, biofilm-related microorganisms, and mucosal tissue — often with minimal pain or difficulty. Science is converging naturally according to common, underlying biological principles, and NIDCR will adapt by establishing firmer connections that reflect these commonalities between oral and general health care practices.
Support research toward precise classification, prevention, and treatment of dental, oral, and craniofacial health and disease.
Ongoing analyses of genomic information in many fields of biomedicine are uncovering new approaches for diagnosing and managing disease based on molecular signatures, rather than relying mainly on symptoms and clinical assessment. NIDCR will continue its support of research toward the development of user-focused, point-of-care technologies that detect dental, oral, and craniofacial health problems in a range of diverse settings, including underserved, low-resource communities nationwide and internationally. This is a first step toward developing effective and personalized disease-management strategies.
NIDCR will support an array of complementary research projects pertaining to physical, functional, and biochemical indicators of disease, including biomarkers — especially those with potential utility for clinical practice. Already in progress is an NIDCR-supported research project that recently yielded a miniaturized, portable nanobiochip that uses nanoliter volumes of saliva to identify biomarkers for a multitude of diagnostic purposes.37
Progress toward the development of personalized and precision health care requires intensive, interdisciplinary research collaborations, and NIDCR will vigorously encourage the establishment of such team efforts. In partnership with stakeholders and other NIH units with relevant interest and expertise, the Institute will foster the development and validation of imaging techniques that promise to increase risk-assessment accuracy for treatment of dental, oral, and craniofacial diseases and disorders. In particular, NIDCR will encourage focused research on specialized imaging and other technologies to trace both physiological and pathological pathways and processes, recruiting needed expertise from quantitative disciplines such as engineering, computer science, materials science, and physics. NIDCR will continue to support efforts to facilitate reconstruction and regeneration of diseased or damaged oral and craniofacial tissues and organs through biological, chemical, bioengineering, and biomaterials research approaches.
The oral cavity is a key entry point for both healthful nutrients and pathogens. Its accessibility and cellular and tissue complexity enable development of novel drug delivery systems for the dental, oral, and craniofacial complex, as well as for other areas of the body such as the lungs or intestinal tract. NIDCR will encourage basic and clinical research to determine the specificity and effectiveness of orally administered substances for manipulating various physiological processes with precisely controlled release kinetics.
Engage primary care providers and health specialists toward individualized, evidence-based health assessment, disease prevention, and treatments.
Personalized oral health must encompass interactions between individuals and their health care providers, families, and communities, as well as the roles played by the health care system. NIDCR will increase efforts to integrate oral health into the broader body of health research initiatives and facilities, as well as within overall clinical care infrastructures. NIDCR will encourage multidisciplinary and transdisciplinary43 interactions among providers within Federally Qualified Health Centers44 and other community-based settings, as well as in non-traditional patient-care settings. The Institute also supports research to determine ways to enhance patient-provider communication, which may have numerous health benefits for individuals and families.
Poor oral health often co-occurs with other health conditions such as obesity, mental illness, substance abuse, and injury/trauma.45,46 NIDCR will support multidisciplinary research to determine contributions to oral health from common disease risk factors. These include unhealthy diet, poor hygiene, tobacco and alcohol use, stress, poverty, and lack of access to dental and general health care.
Partner with public and private organizations to improve oral health.
As an NIH component with an expansive mission, NIDCR will pursue opportunities to partner with stakeholders in areas that will help advance the Institute’s goals toward tailoring oral health for individuals, groups, and communities. In particular, these areas will include i) expanding communication among research, practice, educational, advocacy, and public health communities, ii) developing and commercializing products, and iii) addressing global health challenges.
NIDCR will participate in all trans-NIH opportunities that influence advancement of oral health research and research training. The NIH Common Fund will enable NIDCR to extend its reach into efforts related to workforce growth and diversity, basic behavioral and social sciences, ’omics science, computational biology/informatics, and other areas. As a member of the NIH Pain Consortium,47 NIDCR will promote its pain research agenda via collaboration among researchers across the many NIH Institutes and Centers that have programs and activities addressing pain (see “NIDCR Research Addresses the Many Faces of Pain”).
Public transparency in NIDCR’s research activities is mutually beneficial for the Institute and its stakeholders, adding diverse perspectives and building both understanding and trust. NIDCR will continue to enhance its digital media capabilities with the use of online resources and social media to foster relationships with the public, grantees, and funding/policy collaborators. In November 2013, NIDCR teamed with the Delta Dental Plans Association and the Institute for Oral Health by hosting the symposium “Science and Dentistry in Action: Leading the Way Towards Better Health.” The meeting launched an effort to bring research and clinical practice communities together for interactive learning and discussion of current areas of science and practice. NIDCR will conduct similar activities that encourage learning and relationship-building on an ongoing basis.
A key aspect of the NIDCR mission is fostering the timely transfer of health-related knowledge gained from research to members of the public, health professionals, researchers, and policy-makers — promoting the transformation of health knowledge to health care in ways that meet the needs of individuals and communities. The Institute achieves this goal through its varied interactions with industry and other health-related Federal agencies. The Federal Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Programs offer special opportunities to match emerging technologies with NIDCR mission needs.
One case in point is an NIDCR-funded SBIR grant to a small company that brought specialized, point-of-care computed tomography (CT) scanners from laboratory to market in three years with no other financial support. Cone-beam CT has become particularly popular in oral and maxillofacial surgery, endodontics, implant dentistry, and orthodontics, because the images provide three-dimensional information and higher resolution than the two-dimensional data provided by a conventional X-ray image. In addition to installing dental scanners worldwide, the company has also produced a compact CT scanner for high-resolution bone imaging of the sinuses, temporal bones, and skull base and continues to develop new products.
NIDCR will sustain its longstanding relationships with global partners, including international health offices within the U.S. government and non-governmental entities (see “Oral Health Research Across the Globe”). These ventures align with NIDCR’s research-based mission that advances dental, oral, and craniofacial research for the benefit of health. They enable the Institute to partner with others to improve oral health and oral health research, to enhance diversity efforts in the United States, as well as to contribute to the integration of oral health and general health.
Body: Heal Thyself
What if a damaged tooth or diseased gingiva — or a broken jaw — could heal itself quickly and effectively with a natural repair kit delivered promptly to the injured or diseased site? This could someday soon become reality as a result of impressive progress in NIDCR-supported research that aims to understand how to use natural physiological processes as therapies. Two examples are immune-system modulation that redirects potentially harmful inflammation and the use of stem cells in regenerative medicine approaches.
One promising application for the development of such natural repair kits is periodontal disease, which is a group of conditions that affect the periodontium, the collection of specialized tissues that surround and support teeth and connect them to the bones of the face. Periodontal disease is a health issue affecting one-half of American adults.38 It is characterized by red, swollen, and painful gingiva, and in severe cases, bone destruction. It is caused by constant exposure to a microbial community called a biofilm, which envelops the teeth and gingiva. When immune cells attack bacterial invaders in the mouth, an over-exuberant response can result in persistent inflammation that progressively degrades soft tissue and bone.
NIDCR-funded scientists are learning the step-by-step process that immune cells and natural substances use in the periodontium, and they are devising ways to interrupt or deliberately change it to control inflammation that can be problematic when unchecked. For example, researchers working with a mouse model of periodontal disease developed a system of polymer microspheres that slowly release a substance that attracts T-regulatory immune cells to injured or diseased oral tissue.39 These T cells are often absent at diseased sites, and re-introducing them allows them to act like local police toward other immune system components, tamping down inflammation and limiting the breakdown of bone, leading to natural healing.
Other NIDCR-funded research on natural repair involves a group of substances called lipoxins. The body creates these and other similar molecules called resolvins naturally from fatty acids, and their production is enhanced in the presence of aspirin.40 Studies in animal models have shown that lipoxins reduce cellular inflammation better than current non-opioid pain relievers, and resolvins also appear to have bone-preserving properties.41 A lipoxin rinse is currently being developed by NIDCR-funded scientists as treatment for gingivitis and the first human studies are planned.
Harnessing the regenerative properties of stem cells, other NIDCR-funded scientists are testing the ability of mesenchymal stem cells, or MSCs, to re-grow bone damaged by craniofacial disease or injury.42 MSCs in oral tissues have the ability to become bone, cartilage, or fat, depending on the body’s needs. Researchers are also using MSCs taken from gingiva and bone tissue to study wound healing and scar formation, as well as to investigate the complex interactions between immune cells in the mouth and various oral structures.
NIDCR-Funded Clinical Studies
NIDCR funds extramural and intramural clinical research that addresses a range of scientific questions related to the Institute’s mission.
Selected examples include:
- Assess fluoride treatment of dental decay with polarization-sensitive optical coherence tomography
- Define biomarkers of periodontal disease progression
- Characterize suspicious oral lesions using novel lab-on-a-chip ensembles
- Investigate genetic mutations causing amelogenesis imperfecta, dentinogenesis imperfecta, or dentin dysplasia
- Identify genetic factors contributing to oral health disparities in Appalachia
- Conduct genetic studies of temporomandibular disorders (TMD)
- Image early-caries lesions with near-infrared light
- Define immune control of Kaposi’s sarcoma-associated herpesvirus infection
- Determine mechanisms and treatment response of aggressive periodontitis in children
- Determine the natural history of cracked teeth (a National Dental Practice-Based Research Network study)
- Define the perivascular niche for salivary gland cancer stem cells and their resistance to therapy
- Predict caries risk in underserved toddlers in primary health care settings
- Estimate the prevalence of oral human papillomavirus (HPV) infections in the United States
- Determine the role of HPV in head and neck squamous cell cancer
- Establish the safety and feasibility of administration of DNA vaccine in HPV-16 associated head and neck cancer patients
- Investigate single-suture craniosynostosis
- Investigate factors associated with the onset and transition from acute to chronic TMD
NIDCR Research Addresses the Many Faces of Pain
According to the 2011 Institute of Medicine report “Pain in America,” chronic pain costs the United States up to $635 billion each year in medical treatment and lost productivity.48 To anyone who has either experienced chronic pain or knows someone who has, the costs are truly immeasurable. A multitude of conditions cause chronic pain. These include chronic fatigue syndrome, endometriosis, fibromyalgia, interstitial cystitis, irritable bowel syndrome, chronic headache, temporomandibular disorders, or TMD, and vulvodynia. For reasons that are not thoroughly understood, all of these conditions exact a bigger toll on women than on men. Often an injury or health problem like an infection triggers short-term, or acute, pain, which can then transform into a years- or even decades-long health nightmare. Why do some pain conditions, and not others, turn into longstanding problems? Which treatments work for short- and long-term pain, and can anything be done to mitigate the suffering of millions of Americans?
NIDCR has been a long-time supporter of research on pain in general, and on specific painful oral conditions such as TMD, a group of conditions that can cause intense jaw and facial pain. Common TMD symptoms include pain from chewing or in the jaw joint, limited jaw opening, painful clicking, and popping or grating in the jaw joint when opening or closing the mouth. Research has shown that people with TMD also often have other, related chronic painful conditions such as fibromyalgia and irritable bowel syndrome. Scientists suspect that the overlap of chronic pain conditions is not coincidental, and they are looking for common features in the susceptibility, severity, and progression of various chronic pain conditions — with the twin goals of understanding the cause of pain and determining treatments effective for several conditions at once.
NIDCR supports a wide range of basic research investigating how pain begins as well as studies focused on determining novel ways to treat pain, including non-opioid analgesics that control inflammation. NIDCR also collaborates extensively with the NIH community to tackle the problem of chronic pain by co-funding a range of multidisciplinary and interdisciplinary basic and clinical research approaches. The seven-year Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA I) study aimed to identify causes of first-onset TMD. The results, published in 2013, indicate that a broad range of factors such as sociodemographics, health status, clinical orofacial factors, psychological function, and pain sensitivity influence the course of TMD.49 The follow-up study, OPPERA II, will identify risk factors that predict whether acute TMD will transition into a chronic condition. OPPERA II will also identify genetic aspects and other risk factors that determine whether acute TMD will develop as a single condition or in conjunction with other chronic pain conditions, including headache, low back pain, irritable bowel syndrome, and widespread body pain.50