Faculty Bibliography

BACKGROUND: Since their first review of microsurgical correction of facial contour deformities in 19 patients with craniofacial malformations, the authors have treated an additional 74 patients (n = 93). The authors review indications, choices, safety, efficacy, complications, and technical refinements. A treatment algorithm is presented. METHODS: A retrospective chart review of all patients who underwent microvascular reconstruction of the face and all patients with craniofacial dysmorphology was performed. Between 1989 and 2004, a total of 93 patients with the following diagnoses were identified: craniofacial microsomia (n = 73), Treacher Collins syndrome (n = 8), and severe orbitofacial cleft (n = 12). All patients underwent microsurgical facial reconstruction with a superficial inferior epigastric, groin, or circumflex scapular flap. Flap revisions, complications, and non-free flap related surgery were reviewed. RESULTS: The mean age at microvascular reconstruction was 11 years (range, 4 to 27 years). Flap choices included the following: superficial inferior epigastric (n = 4), groin (n = 3), and circumflex scapular (n = 105). Seventy-six patients underwent unilateral and 17 patients underwent bilateral (one of 17 simultaneous) reconstructions. Postoperative complications included partial flap loss (n = 1), reexploration (n = 1), hematoma (n = 5), and cellulitis (n = 5). All patients had subjective improvement in facial contour, symmetry, skin tone, and color. Most patients underwent additional non-free flap procedures including mandibular distraction and ear reconstruction. CONCLUSIONS: Microsurgical flaps have markedly improved the authors' ability to restore craniofacial contour in patients with craniofacial malformations. In selected patients, the authors choose primary midface augmentation with free vascularized tissue to restore form and function. Microsurgical flaps in patients with craniofacial malformations are safe, effective, and reliable

The vertical rectus abdominus myocutaneous (VRAM) flap is a valuable option for tongue reconstruction. However, the traditional inset (skin to remaining oral mucosa) obviates a more anatomic reconstruction. Eight patients underwent total or subtotal glossectomy with VRAM reconstruction. The muscle inset was supported at the inferior mandibular border attached to the remaining lingual mucosa or gingiva. The neotongue, consisting of skin and subcutaneous fat, was sutured posteriorly to the remaining tongue base, and the other surfaces were trimmed and left unsutured. Reconstruction was successful in all patients. The neotongue assumed palatal configuration, and within 2 weeks uniform granulation tissue followed by mucosalization occurred. One year postoperatively, all patients tolerated ad lib diets, spoke intelligibly, were gastrostomy tube and tracheotomy free and had no evidence of aspiration. This neotongue sits on the mandible under voluntary control, permitting effective obturation against the hard palate and providing successful speech and swallowing

The hedgehog family of morphogens (sonic [Shh], Indian, and desert hedgehog) are central regulators of embryologic growth and tissue patterning. Although recent work implicates Shh in postnatal tissue repair and development, conclusive evidence is lacking. Here, we demonstrated the importance of Shh in wound repair, by examining the effects of cyclopamine, a specific inhibitor of the Shh signaling cascade, on tissue repair. Using a murine-splinted excisional wound model, which attenuates wound contraction in this loose-skinned rodent, we established that, by all measures (wound closure, epithelialization, granulation formation, vascularity, and proliferation), wound healing was profoundly impaired when Shh signaling was disrupted. Because embryonic disruption of Shh is associated with distinct phenotypic defects, our findings invite investigation of the potential role of Shh signaling under postnatal conditions associated with disregulated wound healing

The ability to affect gene expression via topical therapy has profound therapeutic implications for conditions characterized by open wounds including cutaneous neoplasms, thermal injury, skin disorders and dysfunctional wound healing. Specifically targeting local gene expression avoids systemic toxicity and simplifies treatment. We have developed a new method of topical matrix-based short interfering RNA application to precisely and effectively silence local gene expression in nondelimited wounds

BACKGROUND: The adaptive response of bone to mechanical strain, for which angiogenesis is required, is underscored during fracture healing. Vascular endothelial growth factor (VEGF) and transforming growth factor beta-1 (TGF-beta1) are critical regulators of angiogenesis. The purpose of this study was to examine the effect of strain on the production of VEGF and TGF-beta1. STUDY DESIGN: MC3T3-E1 mouse osteoblasts underwent cyclic strain (low, 0.1 Hz, or high, 0.2 Hz) for 24 or 48 hours. VEGF and TGF-beta1 protein levels were determined by ELISA, and Northern blot analysis was performed for VEGF mRNA. Alkaline phosphatase (an osteoblast differentiation marker) activity was determined by functional enzymatic assay. All measurements were standardized for cell number by crystal violet colorimetric assay. Statistical significance was determined by t-test, ANOVA, and the Tukey-Kramer test. RESULTS: Protein production of VEGF and TGF-beta1 was dose-dependently elevated by strain (p < 0.05); alkaline phosphatase did not rise significantly. Northern blot analysis of strained osteoblast cells demonstrated increased VEGF mRNA. Cyclic strain was found to be progressively destructive in a dose-dependent manner, causing 51% and 70% decreases in cell number under low and high strain, respectively (p < 0.01). CONCLUSIONS: We demonstrated simultaneous, dose-dependent increases in VEGF and TGF-beta1 protein production by osteoblastic cells in response to increasing strain. VEGF mRNA also increased in response to strain. This strain-induced increase in angiogenic cytokines suggests a potential mechanism by which injured bone may recruit a new blood supply. But we also found increasing strain to increase cellular toxicity, suggesting that cyclic mechanical strain may select for a subpopulation of osteoblasts