Faculty Bibliography

Delayed diabetic wound healing is, in part, the result of inadequate endothelial progenitor cell (EPC) proliferation, mobilization, and trafficking. Recently, we developed a serum-free functional culture system called the quality and quantity culture (QQc) system that enhances the number and vasculogenic potential of EPCs. We hypothesize that QQc restoration of diabetic EPC function will improve wound closure. To test this hypothesis, we measured diabetic c-kit(+)Sca-1(+)lin(-) (KSL) cell activity in vitro as well as the effect of KSL cell-adoptive transfer on the rate of euglycemic wound closure before and after QQc. KSL cells were magnetically sorted from control and streptozotocin-induced type I diabetic C57BL6J bone marrow. Freshly isolated control and diabetic KSL cells were cultured in QQc for 7 days and pre-QQc and post-QQc KSL function testing. The number of KSL cells significantly increased after QQc for both diabetic subjects and controls, and diabetic KSL increased vasculogenic potential above the fresh control KSL level. Similarly, fresh diabetic cells form fewer tubules, but QQc increases diabetic tubule formation to levels greater than that of fresh control cells (P < 0.05). Adoptive transfer of post-QQc diabetic KSL cells significantly enhances wound closure compared with fresh diabetic KSL cells and equaled wound closure of post-QQc control KSL cells. Post-QQc diabetic KSL enhancement of wound closure is mediated, in part, via a vasculogenic mechanism. This study demonstrates that QQc can reverse diabetic EPC dysfunction and achieve control levels of EPC function. Finally, post-QQc diabetic EPC therapy effectively improved euglycemic wound closure and may improve diabetic wound healing.

The mechanotransduction mechanisms linking distraction device activation to new bone formation remain unknown. We hypothesize that the tension stress of activation during distraction osteogenesis is transmitted through lacunocanalicular fluid flow to initiate the osteogenic signaling cascade. Adult Sprague-Dawley rats (N = 24) were subjected to mandibular osteotomy and application of an external distraction device. After a 3-day latency period, half the animals (n = 12) underwent device activation at 0.25 mm twice daily for 6 days (total activation, 3 mm), and the other half (n = 12) had no activation. On day 10, the animals were injected with fluorescent reactive red lacunocanalicular tracer before killing. Mandibles were harvested, embedded, and sectioned, and reactive red epifluorescence lacunocanalicular flow was measured. Protein was harvested for focal adhesion kinase 1 (FAK1), NESPRIN1, SUN1, LAMIN A/C, and SMAD1 Western blotting as well as for bone morphogenetic protein (BMP)-2 enzyme-linked immunosorbent assay and alkaline phosphatase assay. Lacunocanalicular fluid flow was significantly greater in the distracted samples (60.5 +/- 14 vs 10.3 +/- 4 molecules of equivalent soluble fluorochrome per megapixel, P = 0.01). Flow distribution demonstrated the highest lacunocanalicular flow near the center of the distraction gap. Increased lacunocanalicular flow resulted in increased FAK1 (P = 0.009), NESPRIN1 (P = 0.01), SUN1 (P = 0.01), and LAMIN A/C (P = 0.008) expression. Focal adhesion kinase 1 activation in the presence of BMP-2 protein expression (P = 0.001) resulted in increased intranuclear SMAD1 phosphorylation (P = 0.04) and alkaline phosphatase activity (P < 0.0001). These findings suggest that activation of the distraction osteogenesis device affects cellular response through changes in lacunocanalicular fluid flow.

Statement of the Problem: The use of free osseous flaps has become the gold standard for reconstruction of complex mandibular defects. Popularized by Hidalgo1 in 1989, the free fibula transfer has become the operation of choice for these indications. While this operation has become routine; contouring of the flap using wedge osteotomies, as well as its inset remain operator dependent and imprecise. At our institution we have attempted to make this process more uniform and reproducible through the use of virtual planning and pre-fabricated cutting jigs. We have previously reported our experience on computer-aided design and manufacturing;2 however the purpose of this study was to review our series of free fibula mandibular reconstructions using these adjunctive technologies. Methods: Prior to surgery all patients underwent CT scanning of the face and bilateral lower extremities. These images were then transmitted to an outside vendor. In consultation with both the ablative and reconstructive teams, a surgical plan was devised and performed virtually, cutting jigs for both creation of the mandibular defect and for fibular osteotomies were fabricated, and a stereolithicmodel that allows for precise pre-surgical bending of a reconstruction platewas created. The rest of the surgical procedure was performed in standard fashion. Following IRB approval, all cases between 2009 and 2012 were identified and retrospectively reviewed. In addition to patient demographics, the charts were reviewed for surgical indications, microvascular anastomoses, use of a skin paddle, use of a "double barrel", timing of dental implant placement (immediate versus delayed), and timing of dental prosthetic rehabilitation (immediate versus delayed). Methods of Data Analysis: This was a retrospective chart review from 2009 to the present. Fifty-four reconstructionswere identified as having undergone presurgical virtual planning and subsequent surgery for mandibular reconstruction with microvascular free fibula transfer. Patient!

The aim of this study was to present our experience with reanimation of facial palsy (FP) following tumor extirpation in pediatric patients and to analyze the functional outcomes based on different types of procedures performed considering demographic and electrophysiological data of the patients. Sixteen patients with FP post-tumor extirpation who underwent facial reanimation were reviewed. Three independent assessors evaluated the preoperative and postoperative videos using the Terzis' grading scale for eye closure, smile, depressor and overall esthetic and functional outcomes. Preoperative and postoperative electromyographic interpretations and the effect of demographic variables were also evaluated. There was significant improvement in all the patients regarding overall esthetic and functional outcomes (p < 0.0001). Good and excellent overall esthetic and functional outcomes were observed in 62.50% of the patients (n = 10). The difference between preoperative and postoperative EMG results was of statistical significance (p < 0.0001 for each target re-innervated). Better results were observed in younger patients (