Developmental biology and genetics of craniofacial tissues
Morphogenesis and stem cell-mediated tissue engineering
Craniofacial birth defects, including cleft lip and palate, craniosynotosis, tooth agenesis and other syndromes involving the facial structures, occur in approximately 1 per 500 live births in the United States.
Our investigators are studying the role of genes and proteins, including the signaling molecules involved in palate, cranial sutures, tooth and bone development; genetic etiology of tooth agenesis; molecular control of odontoblast differentiation, and the use of tooth-derived stem cells for the regeneration of the dentin-pulp complex.
- Groppe (BMP structure, function & signaling)
- Svoboda (Palate development; cell-matrix communication)
Temporomandibular joint (TMJ) development and response to pain
TMJ disorders are reported more frequently in females than in males, implying that the different concentrations and patterns of sex hormones are a potential cause for this observed gender disparity. The aim of the studies is to provide new targets for drugs that would be efficacious in treating female patients with TMJ disorders involving inflammation.
Studies are being conducted in the areas of hormonal influence on pain and inflammation in the TMJ and feeding behavior as a model for studying TMJ pain. The research focuses on the development and regulation of the inflammatory responses, particularly crosstalk between the nervous and immune systems; identification of potential targets for therapeutic intervention in the treatment of inflammation and pain; characterization of age, gender and ethnic differences in the pathogenesis of acute and chronic inflammation; elucidation of signal transduction mechanisms during inflammatory joint diseases.
Another research group is concentrating on the unique structural and growth properties of the TMJ cartilage; influence of growth hormone on the growth of the craniofacial skeleton; interaction of growth hormone and mandibular posture in the regulation of condylar cartilage proliferation and mandibular growth.
The figure shows the following:
(A) Fluorescent staining for ERα (red) and Gabrα6 (green) indicated that a few cells contain both ERα and Gabrα6 (yellow arrows); representative image of three proestrus rats. Cell nuclei are stained blue with Hoeschst dye.
(B) No fluorescent signal was observed with the addition of primary antibodies. Bar = 20 μM
- Bellinger/Kramer (Influence of sex hormones on TMJ pain &inflammation)
- Tao (Mechanisms underlying oralfacial pain including TMJ Pain)
Mineralized tissue biology, bioengineering and regeneration
Mutations in a protein expressed in bones and teeth, dentin matrix protein 1 (DMP1), cause hypophosphatemic rickets. This discovery led to a current research project examining the function of this protein in normal and abnormal conditions through different animal models. Another project examines the causes of osteoarthritis, a common disease that affects 60% of the aging population, by generating mice that lack a potent growth factor, GEP. These animals develop severe defects in early cartilage development and display signs of osteoarthritis. Studies using this animal model may provide us with naturally-occurring novel therapeutics for the treatment of arthritic diseases.
Other ongoing studies at the dental school are examining the structural properties, biomechanics and modeling of the craniofacial skeleton, specifically to understand the mechanical and elastic properties of craniofacial bone; the evolution of craniofacial form in humans and other primates; the use of digital imaging and biostatistics to illuminate the growth and development of the facial skeleton, particularly in cleft patients.
Knowledge about the structural biology and biomechanics of dental tissues, particularly dentin and bone, can be applied to the design of new dental materials, bioengineered scaffolds, and delivery vehicles needed for tissue regeneration. Projects in this area of study include the testing of novel scaffolds that are conducive for the vascularization and regeneration of dentin and bone matrices.
- Dechow (Biomechanical properties of craniofacial bone; evolution of hominid facial skeleton)
- Feng (Role of dentin matrix protein-1, Bmp receptor 1A, β catenin, periostin & loading during development)
- Qin (Role of DSPP and DMP1 in dentinogenesis and osteogenesis)
- Liu (Biomimetic materials and scaffold design, synthesis, and application for tissue regeneration; biomedical devices with controlled drug delivery)
- Varanasi (Tissue engineering and nano-scale fabrication of bioactive glasses and ceramics)
Development of biomedical devices for dentistry
Implant use in dentistry
The use of implants in high-risk patients such as diabetics and smokers is controversial. Several groups at the college are testing new implant surfaces and thread designs to improve the success rate of placing implants in this hard-to-treat group of patients. These studies include sponsored research agreements with outside companies, as well as studies testing new patented inventions devised by college faculty members.
Another controversial subject is whether implant placement is more efficient and produces better treatment outcomes than conventional root canal treatment. A large ongoing clinical study is evaluating the amount of time it takes patients to recover full chewing function after receiving an implant versus regular endodontic treatment of single teeth. Patient satisfaction is also being gauged.
Mini-implants (or miniscrews) are increasingly being used as orthodontic anchoring devices rather than teeth. Current orthopedic appliances require patient compliance, making treatment outcomes unpredictable. The use of miniscrews as orthodontic anchoring devices is now being tested in both clinical and animal studies focusing on whether miniscrews provide more stable anchorage, more consistent forces, and therefore, better treatment outcomes and shorter treatment times than conventional orthopedic devices.
Bone augmentation options in the craniofacial region
The repair of craniofacial defects often requires more bone than is available from the patients themselves. College faculty are partnering with medical centers and with industry to test new bone substitute materials and new carriers of growth factors known to stimulate new bone formation
The repair of full-thickness bone defects in the mandible after resection of cancerous bone tissue is a lengthy procedure with a high risk of the loss of the full function of the jaw (such as the ability to place implants or dentures on the repaired bone). Dental school faculty and students have invented, patented and tested a new new device capable of using the body's own bone repair mechanisms to fully heal these defects, which will allow full rehabilitation of the patient's normal chewing function. Commercialization options are currently being explored.
- Opperman (Design of distraction devices for mandibular & sutural growth; Miniscrews as anchoring devices in orthodontics).