Faculty Bibliography

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

INTRODUCTION: Treacher Collins syndrome is an autosomal dominant mandibulofacial dysostosis with characteristic hard- and soft-tissue facial abnormalities. These include ocular malformations, ear malformations, and hypoplasia of the facial skeleton, especially of the malar bones and mandible. Traditionally, surgical correction of the facial abnormalities has focused on skeletal reconstruction to restore facial form and symmetry. In this report, we describe the use of customized parascapular free flaps, after standard reconstructive surgeries, for the correction of defects of facial contour in Treacher Collins patients. In most cases, bony reconstruction of the zygoma or periorbita is not required. METHODS: From June 1995 to December 2003, 8 patients with Treacher Collins syndrome underwent microsurgical correction of facial contour using 16 free flaps. In all patients, staged parascapular free flaps were used for reconstruction. The microvascular technique involved a 2-team approach with simultaneous ipsilateral parascapular flap harvest and facial pocket dissection. The flaps were contoured, revascularized (14 superficial temporal vessels, 2 facial vessels), and inset. No vein grafts were used. The patients were followed for a minimum of 1 year, and postoperative evaluation included medical photography, visual assessment, and evaluation by the patient and family. RESULTS: Seven patients had previous facial skeleton correction using craniofacial techniques. The age at operation ranged from 4-19 years. Sixteen parascapular free flaps were used in the 8 patients. Postoperative complications were limited to 1 hematoma. There were no partial or total flap losses. All of the patients had improved facial contour and symmetry. Overlying skin tone and color similarly improved. CONCLUSION: After traditional skeletal reconstruction for the complex craniofacial defects of Treacher Collins syndrome, deficiencies in facial contour and symmetry usually persist. Customized soft-tissue free flaps can be employed to differentially resurface these defects and achieve optimal esthetic results in these challenging patients

The carpometacarpal (CM) joint of the thumb is commonly affected by osteoarthritis. The strength required for a first CM ligament reconstruction depends on the forces across the joint. If these forces are rebalanced to reduce the requirements necessary to prevent subluxation, reconstructive requirements are lowered and surgical dissections reduced. A method to achieve this goal based on Landsmeer's zig-zag compression concept is presented. Fifteen consecutive patients (11 women; mean age, 63 years) with pantrapezial osteoarthritis were selected over a 2-year period to undergo this novel procedure. After standard trapezial resection, trapezoidal hemiresection was performed, allowing for medial movement of the first metacarpal base. Following the zig-zag concept, the first metacarpophalangeal joint reciprocally fell into flexion, decreasing forces causing subluxation of the first metacarpal base. A saddle-like suspension under the metacarpal base was created using the trapezial capsule. All 15 patients had excellent outcomes with elimination of pain, early recovery of mobility and power, and no recurrent subluxations. The durability of the procedure was confirmed clinically and radiologically. The medial relocation of the first metacarpal base rebalances and attenuates the normal deforming forces thereby eliminating the need for a strong CM ligament reconstruction