Faculty Bibliography

Impaired repair of skin defects is a major complication of diabetes; yet, the pathophysiology of diabetic (db) wound healing remains largely opaque. Here, we investigate the role of humoral factors in modulating db wound repair by generating chimeric animals through parabiotic joining of wild-type (wt) and diabetic (db/db) mice. This strategy allows wounds on healing-deficient db/db mice to be exposed to factors derived from the wt circulation at physiologically appropriate concentrations. When compared with db controls, chimeric db/db animals showed significantly improved healing of full-thickness, cutaneous wounds, with enhanced granulation tissue formation, angiogenesis, cell proliferation, and collagen deposition. Glycemic control was unaffected by parabiosis; however, the distribution of circulating leukocytes, altered in db controls, normalized in db-chimeras. Both wt and db cells were recruited from circulation into db wounds, but wt cells never exceeded 20% of total cells. Improved angiogenesis persisted in db-chimeras separated 24 hours after wounding, suggesting the existence of long-term normalizing factors. This study establishes a new model for studying db wound healing, and shows a key role for circulating factors in normalizing wound repair in diabetes.

BACKGROUND: The supraclavicular island flap has been used successfully for difficult facial reconstruction cases, providing acceptable results without using microsurgical techniques. The authors use this regional flap in reconstructing various head and neck oncologic defects that normally require traditional regional or free flaps to repair surgical wounds. METHODS: A pedicled supraclavicular artery flap was used to reconstruct head/neck oncologic defects. Complications and functional outcomes were assessed. RESULTS: Head and neck oncologic patients underwent tumor resection followed by immediate reconstruction using a supraclavicular artery island flap. Ablative defects included neck, tracheal-stomal, mandible, parotid, and pharyngeal walls. All flaps (n = 18) were harvested in less than 1 hour. All ablative wounds and donor sites were closed primarily and did not require additional surgery. Major complications included a complete flap loss when the vascular pedicle was inadvertently divided and pharyngeal leaks. The leaks resolved without surgical intervention, and both patients regained the ability to swallow using their neo-esophagus. Minor complications included donor-site wound dehiscence and cellulitis. None of the patients reported functional donor-site morbidity. CONCLUSIONS: This thin flap is easy and quick to harvest, has a reliable pedicle, and has minimal donor-site morbidity. It is now the authors' flap of choice for many common head and neck reconstructive problems. Early experience using the supraclavicular artery island flap suggests that it is an excellent flap option for head and neck oncologic disease patients.

Laryngopharyngeal oncologic resections produce complex reconstructive problems, requiring dependable robust flaps to restore form and function. Current options include morbid local-regional flaps or free tissue transfers. The supraclavicular artery flap (SAF) offers a great new option. Partial pharyngeal oncologic defects were reconstructed with pedicled SAFs. Handheld Doppler probes marked the pedicle preoperatively. Flaps were design based upon the dopplered vascular anatomy. Complications and functional outcomes were assessed. All flaps (n = 6) were harvested in under 1 hour with uneventful postoperative recoveries. Ablative wounds and donor sites were closed primarily. Two patients had small controlled leaks because of preoperative radiation and overly aggressive oral intakes, that subsequently resolved. There were no functional donor site morbidities. We describe a novel application of the SAF for pharyngeal reconstructions after laryngopharyngeal cancer ablation. This thin, reliable, easy to harvest, low morbidity flap is an excellent reconstructive option for pharyngeal reconstructions.

Periosteal grafts can aid in bone repair by providing bone progenitor cells and acting as a barrier to scar tissue. Unfortunately, these grafts have many of the same disadvantages as bone grafts (donor site morbidity and limited donor sites). In this article, we describe a method of synthesizing a periosteum-like material using acellular human dermis and osteoblasts or mesenchymal stem cells (MSC). We show that osteoblasts readily attach to and proliferate on the acellular human dermis in vitro. In addition, osteoblasts retained the potential for differentiation in response to bone morphogenetic protein stimulation. Cells grown on the acellular human dermis were efficiently transfected with adenoviruses with no evidence of cellular toxicity. To assess for in vivo cell delivery and bone-forming potential, the acellular human dermis was seeded with green fluorescent protein (GFP)-positive MSCs, transfected with bone morphogenetic protein 2, wrapped around the adductor muscle in syngeneic mice, and used to treat critical-sized mandibular defects in nude rats. After 3 weeks, GFP-positive cells were still present, and bone had replaced the interface between the muscle and the constructs. After 6 weeks, critical-sized bone defects had been successfully healed. In conclusion, we show that an acellular human dermis can be used to synthesize a tissue-engineered periosteum capable of delivering cells and osteoinductive proteins.

Societal changes, including the aging of the US population and the lack of routine dental service coverage under Medicare, have left many seniors unable to afford any dental care whatsoever, let alone the most advanced treatments.(1) In 2004, the Columbia University College of Dental Medicine and its partners instituted the ElderSmile program in the largely impoverished communities of Harlem and Washington Heights/Inwood in New York City. The long-term goal of this program is to improve access to and delivery of oral health care for seniors; the short-term goal is to establish and operate a network of prevention centers surrounding a limited number of treatment centers. Preliminary results indicate substantial unmet dental needs in this largely Hispanic and Black elderly population.

PURPOSE: The present study assessed damage to the inferior alveolar nerve (IAN) following nerve lateralization and implant placement surgery through optical and transmission electron microscopy (TEM). MATERIALS AND METHODS: IAN lateralization was performed in 16 adult female rabbits (Oryctolagus cuniculus). During the nerve lateralization procedure, one implant was placed through the mandibular canal, and the IAN was replaced in direct contact with the implant. The implant was placed in the right mandible, and the left side was used as a control (no surgical procedure). After 8 weeks, the animals were sacrificed and samples were prepared for optical and TEM analysis of IAN structural damage. Histomorphometric analysis was performed to determine the number and cross-sectional dimensions of nerve fascicles and myelin sheath thickness between experimental and control groups. The different parameters were compared by one-way analysis of variance at the 95% significance level. RESULTS: Alterations in the perineural and endoneural regions of the IAN, with higher degrees of vascularization, were observed in the experimental group. TEM showed that the majority of the myelinated nerve fibers were not affected in the experimental samples. No significant variation in the number of fascicles was observed, significantly larger fascicle height and width were observed in the control group, and significantly thicker myelin sheaths were observed in the experimental samples. CONCLUSION: IAN lateralization resulted in substantial degrees of tissue disorganization at the microstructural level because of the presence of edema. However, at the ultrastructural level, small amounts of fiber degeneration were observed.

The objective of this study was to physico/chemically characterize and evaluate the in vivo performance of two nanothickness ion beam assisted depositions (IBAD) of bioceramic coatings on implants in a beagle model. Alumina-blasted/acid-etched (AB/AE) Ti-6Al-4V implants were subjected to two different IBAD depositions (IBAD I and IBAD II), which were physico/chemically characterized by SEM, EDS, XPS, XPS + ion-beam milling (depth profiling), XRD, AFM, and ToF-SIMS. A beagle dog tibia model was utilized for histomorphometric and biomechanical (torque) comparison between AB/AE, IBAD I, IBAD II, and plasma-sprayed hydroxyapatite (PSHA) coated implants that remained in vivo for 3 and 5 weeks. The coatings were characterized as amorphous Ca-P with high Ca/P stoichiometries with thicknesses of an order of magnitude difference (IBAD I = 30-50 nm and IBAD II = 300-500 nm). The histomorphometric and biomechanical testing results showed that the 300-500 nm thickness deposition (IBAD II) and PSHA positively modulated bone healing at early implantation times.

The objective of this study was to evaluate the morphology and integration status of 30 human retrieved plateau root form implants. Thirty plateau design root form implants that were in function from 8 to 13 years were retrieved from patients due to prosthetic reasons. Following surgical removal, the samples remained in 10% buffered formaline for 7 days. Bone morphology was evaluated by transmitted and polarized light microscopy, and bone-to-implant contact (BIC) histomorphometric assessment was determined through computer software. Irrespective of time in vivo, lamellar bone was observed in close contact with the implant surface and between plateaus. BIC ranged from approximately 20 to approximately 80%. Polarized light microscopy showed a highly directional osteonic morphology between plateaus for most implants. A haversian-like microstructure running perpendicular to and along with the implants' long axis (between plateaus) was observed in regions of cortical and trabecular bone, revealing a unique bone microstructural evolution over time around functionally loaded plateau root form implants.

PURPOSE: The objective of this study was to evaluate the bone response to a nanothickness bioceramic ion beam-assisted deposition (IBAD) on endosteal implants in a canine model. MATERIALS AND METHODS: Alumina-blasted/acid-etched (control) and IBAD-modified (test) implants were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy + ion beam milling, thin-film mode X-ray diffraction, and atomic force microscope. The implants were surgically placed in four dogs' proximal tibiae and remained for 2 and 4 weeks in vivo. Oxytetracycline (10 mg/kg) was administered for bone labeling 48 hours prior to euthanization. Following euthanization, nondecalcified thin sections were prepared for UV and transmitted light microscopy. The amount of bone labeling was evaluated along the length and away from the implant surface by means of a computer software. The % bone-to-implant contact (BIC) was determined for each specimen. One-way analysis of variance at 95% level of significance along with Tukey's post hoc multiple comparisons were utilized for statistical evaluation. The characterization showed Ca- and P-based amorphous coatings with a 20- to 50-nm thickness. RESULTS: In vivo results showed a significant increase in general and site-specific (to 0.5 mm from the implant surface) bone activity for the 4-week test implants compared with the control implants. Bone activity levels decreased as a function of distance from the implant surface for all groups. No significant differences in BIC were observed between groups. CONCLUSIONS: This study showed that both surfaces were biocompatible and osteoconductive and that a time-dependent increase in osteoactivity occurred around the test implants.