Faculty Bibliography

Healthcare systems should be transparent and easy to use and considered a joint venture between the various stakeholders with the goal of improving the diagnosis, treatment and clinical outcomes to control nations' rising costs of healthcare. The stakeholders are many including an educational component, practitioners, payers, government and industry providing the treatment and medications. All of these variables and more contribute to cost escalation. Within this complex framework is the nations' abiliy to provide some level of basic care for public health assurance of its populace possibly through the concept of 'person-centricity'. The Practitioners Engaged in Applied Learning & Research (PEARL) Network was conceived through government funding and has evolved into a not-for-profit private enterprise. The PEARL Network is a hybrid network incorporating the benefits of an academic practice based research network into a practice based translational network with the principles of conducting pharmaceutical level clinical studies for regulatory submission. PEARL incorporates the philosophy of 'person-centricity' and operationalizes it conducting 'person-centric clinical trials.&rsqu

A person-centric clinical trial is inclusive of both the investigator and the person and as such represents point-of-use data generated at the practice level and encompasses both health and disease. Raising the clinical encounter to a research encounter and providing an infrastructure to support a level of quality assurance creates a synergy for efficiency for healthcare delivery. The interface of translational studies and clinical research poses an opportunity, whereby person-centricity can support transparency, facilitate informed consent, improve safety, enhance recruitment and compliance, improve dissemination of results, implement change and help close the translational gap. The model represents robust clinical data from persons of record allowing for improved interpretation of drug/device side-effects and for regulatory reviewers to expedite the approval process.

Detailed methods are provided for the preparation and confocal imaging of cardiac myocyte development and differentiation. Examples include protocols for the analysis of cultured myocytes as well as vibratome sections of hearts from embryonic and adult tissue. Techniques include routine labeling of F-actin with phalloidin as well as multiple labeling protocols for colocalization studies and cell volume analysis.

New methods of teaching gross anatomy are being evaluated as medical and dental schools attempt to find time in their curricula for new content without sacrificing essential anatomical knowledge. This article reports on an innovative method of teaching anatomy at New York University College of Dentistry. In 2005, the instructors completely replaced the dissection of wet cadavers with the study of dissected and sliced plastinated specimens. The shift from cadaver dissection to the study of plastinated specimens was accompanied by other changes in the anatomy course: students study in small, consistent groups; frequent, low-impact quizzes are administered; and the role of the computer is increased as a tool for self-directed study. To assess the course, this study considered students' long-term understanding of anatomy as demonstrated by performance on the National Board Dental Examination (NBDE) Part I, hours of instruction, and student evaluation. The results show that, since 2005, students have had higher NBDE Part I scores, their overall performance has been above the national mean while hours of instruction were 60 percent of the national mean, and student satisfaction increased.

In 2005, the National Institute of Dental and Craniofacial Research / National Institute of Health (NIDCR/NIH) funded the largest initiative to date to affect change in the delivery of oral care. This commentary provides the background for the first study related to periodontics in a Practice Based Research Network (PBRN). It was conducted in the PEARL (Practitioners Engaged in Applied Research & Learning) Network. The PEARL Network is headquartered at New York University College of Dentistry. The basic tenet of the PBRN initiative is to engage clinicians to participate in clinical studies, where they will be more likely to accept the clinical results and to incorporate the findings into their practice. This process may reduce the translational gap that exists between new findings and the time it takes for those findings to be incorporated into clinical practice. The cornerstone of the PBRN studies is to conduct comparative effectiveness research studies to disseminate findings to the profession and improve care. This is particularly important as the majority of dentists practice independently. Having practitioners generate clinical data allows them to contribute in the process of knowledge development and incorporate the results in their practice to assist in closing the translational gap. With the advent of electronic health systems on the horizon dentistry may be brought into the mainstream health care paradigm and the PBRN concept can serve as the skeletal framework for advancing the profession provided there is consensus on the terminology used.

Data from clinical studies generated by Practice Based Research Networks should be generalizable to the profession. For nationally representative data a broad recruitment of practitioners may pose added risks to IRB's. Infrastructure must assure data integrity while minimizing risk to assure that the clinical results are generalizable. The PEARL Network is an interdisciplinary dental/medical PBRN conducting a broad range of clinical studies. The infrastructure is designed to support the principles of Good Clinical Practice (GCP) and create a data audit trail to ensure data integrity for generalizability. As the PBRN concept becomes of greater interest, membership may expand beyond the local community, and the issue of geography versus risk management becomes of concern to the IRB. The PEARL Network describes how it resolves many of the issues related to recruiting on a National basis while maintaining study compliance to ensure patient safety and minimize risk to the IRB.

The potential clinical utility of engineered muscle is currently restricted by limited in vitro capacity of expanded muscle precursor cells to fuse and form mature myofibers. The purpose of this study was to use isotropic skeletal muscle sheets to explore the impact of (1) fibroblast coculture and (2) fibroblast-conditioned media (fCM) on in vitro myogenesis. Muscle sheets were prepared by seeding varying ratios of skeletal myoblasts and fibroblasts on a biomimetic substrate and culturing the resulting tissue in either control media or fCM. Muscle sheets were prepared from two cell subpopulations, (1) C2C12 and NOR-10 and (2) primary neonatal rat skeletal muscle cells (nSKM). In C2C12/Nor-10 muscle sheets fCM conferred a myogenic advantage early in culture; at D1 a statistically significant 3.12 +/- 0.8-fold increase in myofiber density was observed with fCM. A high purity satellite cell population was collected from an initially mixed population of nSKMs via cell sorting for positive alpha 7-integrin expression. On D6, tissue sheets with low fibroblast concentrations (0 & 10%) cultured in fCM had increased average myofiber density (4.8 +/- 0.2 myofibers/field) compared to tissue sheets with high fibroblast concentrations (50%) cultured in control media (1.0 +/- 0.1 myofibers/field). Additionally, fCM promoted longer, thicker myofibers with a mature phenotype.

The foreign body response to medical devices and materials implanted in the human body, including scarring, fibrous encapsulation, and potential rejection, is a longstanding and serious clinical issue. There are no widely acceptable or safe therapies for ameliorating the foreign body response. Clinical complications resulting from the response include disfigurement of silicone prostheses and loss of function of devices such as implanted pacemakers, stents, and shunts. Cellularized implants and stem cells placed in the body are also subject to the foreign body response with the added issue that the regenerative repair intended to be prompted by the graft may be inhibited. Beneficial modification of the body's reaction to implanted materials, medical devices, engineered constructs, or stem cells would be a fundamentally important therapeutic advance.As part of investigating the cellular response, we have developed a model which uses cells isolated from skeletal muscle biopsy, cultured, and proliferated in vitro. These satellite cells, which are mononucleated progenitor cells, reside between the plasma membrane of the muscle fiber and the basal membrane that encompasses the fiber. While usually quiescent, these cells become activated following muscle damage. Once activated, the satellite cells proliferate, migrate to injured muscle, and participate in repair by fusing with existing muscle fibers or by differentiating into new skeletal muscle fibers. Satellite cells have been shown to be heterogeneous populations of stem cells and progenitor cells. We have developed an explant method for isolating, sorting, enriching, and culturing these cells for use in skeletal muscle regenerative medicine to determine if the foreign body response can be inhibited by manipulating the cell-cell communication.

The NIDCR-supported Practice-based Research Network initiative presents dentistry with an unprecedented opportunity by providing a pathway for modifying and advancing the profession. It encourages practitioner participation in the transfer of science into practice for the improvement of patient care. PBRNs vary in infrastructure and design, and sustaining themselves in the long term may involve clinical trial validation by regulatory agencies. This paper discusses the PBRN concept in general and uses the New York University College of Dentistry's Practitioners Engaged in Applied Research and Learning (PEARL) Network as a model to improve patient outcomes. The PEARL Network is structured to ensure generalizability of results, data integrity, and to provide an infrastructure in which scientists can address clinical practitioner research interests. PEARL evaluates new technologies, conducts comparative effectiveness research, participates in multidisciplinary clinical studies, helps evaluate alternative models of healthcare, educates and trains future clinical faculty for academic positions, expands continuing education to include "benchmarking" as a form of continuous feedback to practitioners, adds value to dental schools' educational programs, and collaborates with the oral health care and pharmaceutical industries and medical PBRNs to advance the dental profession and further the integration of dental research and practice into contemporary healthcare (NCT00867997, NCT01268605).

Where does dentistry fit into the field of regenerative medicine? Based on the fact that the goal of regenerative medicine is to restore function to damaged organs and tissues, it is apparent that dentistry, which has long embraced the concept of restoring function of damaged teeth, has embraced this goal from the very beginning. In this brief review we present the opinion that if you take as the primary criterion the restoration of tissue and organ function, dentistry has not only been at the forefront of restorative medicine but actually predates it in practice. We illustrate the depth and breadth of dental regenerative medicine using examples of therapies or potential therapies from our laboratories. These begin with an example from a historical area of strength, dental implant design and fabrication, progress to a more high tech bone scaffold fabrication project, and finish with a stem cell-based soft tissue engineering project. In the final analysis we believe that the restorative nature of dentistry will keep it at the forefront of regenerative medicine.