Faculty Bibliography

BACKGROUND: The free fibula osteocutaneous flap has become the criterion standard for reconstruction of complex mandibular defects. The authors present their institutional experience with optimization of flap contouring and inset using virtual planning and prefabricated cutting jigs. METHODS: All free fibula-based mandible reconstructions performed at the authors' institution using virtual planning technology between 2009 and 2012 were retrospectively analyzed. The authors evaluated a variety of patient and procedural variables and outcomes. A series of cases performed before virtual planning was reviewed for comparison purposes. RESULTS: Fifty-four reconstructions were performed in 52 patients. Patients were divided evenly between a private university-affiliated medical center and a large county hospital. The most common indications were malignancy (43 percent), ameloblastoma (26 percent), and osteonecrosis/osteomyelitis (23 percent). Thirty percent of patients had irradiation of the recipient site and 38 percent had previous surgery. Sixty-three percent of patients received dental implants, with 47 percent achieving functional dentition. Twenty-five percent of patients had immediate dental implant placement, and 9 percent had immediate dental restoration. Postoperative imaging demonstrated excellent precision and accuracy of flap positioning. Comparison with cases performed before virtual planning demonstrated increased complexity of flap design along with reduced operative time in the virtually planned group. CONCLUSIONS: Preoperative virtual planning along with use of prefabricated cutting jigs allows for precise contouring and positioning of microvascular fibula free flaps in mandibular reconstruction. Using this technique, the authors have achieved unprecedented rates of dental rehabilitation along with reduced operative times. The authors believe that virtual planning technologies are an emerging criterion standard in mandible reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

BACKGROUND: : Tumors of the mandible are complex, often requiring replacement of bone, soft tissue, and teeth. The fibula flap has become a routine procedure in large tumors of the jaw, providing bone and soft tissue at the time of the resection. In current practice, dental reconstruction is delayed for 3 to 6 months, leaving the patient without teeth in the interim. This can be disfiguring and anxiety provoking for the patient. METHODS: : In this article, the authors present three patients with benign tumors of the mandible who underwent virtually guided resection, fibula reconstruction, and insertion of an implant-retained dental prosthesis in one operation. In addition, the authors report their early experience using this technique in the maxilla. RESULTS: : The authors present a case series of three patients with benign mandibular tumors and one patient with a benign maxillary tumor who underwent total reconstruction using computer-aided design and computer-aided manufacturing technology in a single stage. CONCLUSIONS: : In the right situation, total mandibular reconstruction is possible in a single stage. This is demonstrated by the successful outcomes of these patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: : Therapeutic, V.

Background The authors describe our current practice of computer-aided virtual planned and pre-executed surgeries using microvascular free tissue transfer with immediate placement of implants and dental prosthetics.Methods All patients with ameloblastomas treated at New York University (NYU) Medical Center during a 10-year period from September 2001 to December 2011 were identified. Of the 38 (36 mandible/2 maxilla) patients that were treated in this time period, 20 were identified with advanced disease (giant ameloblastoma) requiring aggressive resection. Reconstruction of the resultant defects utilized microvascular free tissue transfer with an osseocutaneous fibular flap in all 20 of these patients.Results Of the patients reconstructed with free vascularized tissue transfer, 35% (7/20) developed complications. There were two complete flap failures with consequent contralateral fibula flap placement. Sixteen patients to date have undergone placement of endosteal implants for complete dental rehabilitation, nine of which received immediate placement of the implants at the time of the free flap reconstruction. The three most recent patients received immediate placement of dental implants at the time of microvascular free tissue transfer as well as concurrent placement of dental prosthesis.Conclusions To our knowledge, this patient cohort represents the largest series of comprehensive computer aided free-flap reconstruction with dental restoration for giant type ameloblastoma.

Craniofacial vascularized composite allotransplantation is especially challenging when bony components are required. Matching the complex three-dimensional anatomy of the donor and recipient craniofacial skeletons to optimize bony contact and dental occlusion is a time-consuming step in the operating room. Currently, few tools exist to facilitate this process. The authors describe the development of a virtual planning protocol and patient-specific device design to efficiently match the donor and recipient skeletal elements in craniofacial vascularized composite allotransplantation. The protocol was validated in a cadaveric transplant. This innovative planning method allows a "snap-fit" reconstruction using custom surgical guides while maintaining facial height and width and functional occlusion. Postoperative overlay technology in the virtual environment provides an objective outcome analysis.

Classic tissue engineering paradigms are limited by the incorporation of a functional vasculature and a reliable means for reimplantation into the host circulation. We have developed a novel approach to overcome these obstacles using autologous explanted microcirculatory beds (EMBs) as bioscaffolds for engineering complex three-dimensional constructs. In this study, EMBs consisting of an afferent artery, capillary beds, efferent vein, and surrounding parenchymal tissue are explanted and maintained for 24 h ex vivo in a bioreactor that preserves EMB viability and function. Given the rapidly advancing field of stem cell biology, EMBs were subsequently seeded with three distinct stem cell populations, multipotent adult progenitor cells (MAPCs), and bone marrow and adipose tissue-derived mesenchymal stem cells (MSCs). We demonstrate MAPCs, as well as MSCs, are able to egress from the microcirculation into the parenchymal space, forming proliferative clusters. Likewise, human adipose tissue-derived MSCs were also found to egress from the vasculature and seed into the EMBs, suggesting feasibility of this technology for clinical applications. We further demonstrate that MSCs can be transfected to express a luciferase protein and continue to remain viable and maintain luciferase expression in vivo. By using the vascular network of EMBs, EMBs can be perfused ex vivo and seeded with stem cells, which can potentially be directed to differentiate into neo-organs or transfected to replace failing organs and deficient proteins

Breast cancer often leads to significant alteration of body image and disfigurement of the breast. Reconstruction for breast cancer defects can provide the patient with a restored breast contour. The potential benefit of breast cancer reconstructive surgery is to increase the patient's post-surgical quality of life and alleviate the posttraumatic psychological sequelae of breast cancer surgery. Time of breast cancer diagnosis is an important point of access for patients to receive information on breast reconstruction. Access to this information and plastic surgeons in the early phases of diagnosis is critical to a patient's decision to undergo reconstructive surgery, but is currently underutilized in the United States. Breast cancer reconstruction is a complex process that should be treated in a multidisciplinary fashion. This process must begin with the identification and treatment of psychological issues preceding or accompanying breast cancer diagnosis. These psychological problems should be addressed immediately and can significantly influence a patient's decision toward and level of satisfaction with breast cancer reconstruction. Breast reconstruction continues to be an essential element in helping patients recover from the diagnosis and treatment for breast cancer.

Tissue ischemia promotes vasculogenesis through chemokine-induced recruitment of bone marrow-derived endothelial progenitor cells (EPCs). Diabetes significantly impairs this process. Because hyperglycemia increases reactive oxygen species in a number of cell types, and because many of the defects responsible for impaired vasculogenesis involve HIF1-regulated genes, we hypothesized that HIF1 function is impaired in diabetes because of reactive oxygen species-induced modification of HIF1alpha by the glyoxalase 1 (GLO1) substrate methylglyoxal. Decreasing superoxide in diabetic mice by either transgenic expression of manganese superoxide dismutase or by administration of an superoxide dismutase mimetic corrected post-ischemic defects in neovascularization, oxygen delivery, and chemokine expression, and normalized tissue survival. In hypoxic fibroblasts cultured in high glucose, overexpression of GLO1 prevented reduced expression of both the EPC mobilizing chemokine stromal cell-derived factor-1 (SDF-1) and of vascular epidermal growth factor, which modulates growth and differentiation of recruited EPCs. In hypoxic EPCs cultured in high glucose, overexpression of GLO1 prevented reduced expression of both the SDF-1 receptor CXCR4, and endothelial nitric-oxide synthase, an enzyme essential for EPC mobilization. HIF1alpha modification by methylglyoxal reduced heterodimer formation and HIF1alpha binding to all relevant promoters. These results provide a basis for the rational design of new therapeutics to normalize impaired ischemia-induced vasculogenesis in patients with diabetes

BACKGROUND: Diabetics suffer from vascular dysfunction with increased risks of coronary artery disease and peripheral vascular disease secondary to an impaired ability to respond to tissue ischemia. Because endothelial progenitor cells are known to home to sites of ischemia and participate in new blood vessel growth, the authors examined the effects of diabetes on human endothelial progenitor cell function and peripheral tissue signaling in hypoxia, and determined whether these cells might be a useful cell-based therapy for diabetic vascular complications. METHODS: Circulating human endothelial progenitor cells from type 2 diabetic patients and controls were isolated and subjected to in vitro adhesion, migration, and proliferation assays (n = 5). Cell mobilization and recruitment were studied in vivo in diabetic and nondiabetic environments (n = 6). Exogenous human diabetic and normal cells were analyzed for therapeutic efficacy in a murine ischemia model (n = 6). RESULTS: Adhesion, migration, and proliferation of human diabetic endothelial progenitor cells in response to hypoxia was significantly reduced compared with controls. In diabetic mice, cell mobilization from the bone marrow and recruitment into ischemic tissue was significantly reduced compared with controls. Normal cells injected systemically as replacement therapy in a diabetic mouse increased but did not normalize ischemic tissue survival. CONCLUSIONS: These findings suggest that diabetes causes defects in both the endothelial progenitor cell and peripheral tissue responses to hypoxia. These changes in endothelial progenitor cell function and signaling offer a novel explanation for the poor clinical outcome of type 2 diabetics following ischemic events. Based on these findings, it is unlikely that endothelial progenitor cell-based cellular therapies will be able to prevent diabetic complications