Faculty Bibliography

BACKGROUND: Autogenous fat grafting has been observed to alleviate the sequelae of chronic radiodermatitis. To date, no study has replicated this finding in an animal model. METHODS: The dorsa of adult wild-type FVB mice were shaved and depilitated. The dorsal skin was then distracted away from the body and radiated (45Gy) using a Varian 2300 Linear Accelerator. Four weeks following radiation, 1.5cc fat or sham grafts were placed in the dorsal subcutaneous space. Gross results were analyzed photometrically. The animals were sacrificed at 4 and 8 weeks following fat or sham grafting and their dorsal skin was processed for histologic analysis. Inflammation was assessed by epidermal thickness measurements on H&E stained sections. Vascular density was assessed using CD31 staining. Fibrosis was assessed using Smad-3 and Picrosirius Red staining. RESULTS: Hyperpigmentation and ulceration were grossly improved in fat-grafted mice compared to sham-grafted controls. Epidermal thickness measurements demonstrated decreased thickness in fat-grafted animals at both timepoints (20.6+/-1.5mum vs 55.2+/-5.6mum, p=0.004; 17.6+/-1.1mum vs 36.3+/-6.1mum, p=0.039). Vascular density was decreased in fat-grafted mice compared to sham-grafted at both timepoints (17.5+/-1.3 vessels/hpf vs 29+/-3.5, p=0.055; 13.25+/-1.4 vs 17.0+/-1.6, p=0.003). Intensity of Smad3 staining was significantly decreased in fat-grafted animals at both timepoints (2.77+/-0.3% vs 4.98+/-0.9%, p=0.004; 3.05+/-0.2% vs 5.81+/-0.3%, p=0.011). Picrosirius red staining demonstrated a diminished scar-index in fat-treated animals at both timepoints (.54+/-0.05 vs .74+/-0.07, p=0.034; .55+/-0.06 vs .93+/-.07, p=0.001). CONCLUSIONS: Fat grafting attenuates inflammation in acute radiodermatitis and slows the progression of fibrosis in chronic radiodermatitis

We present the deep femoral artery perforator (DFAP) flap, a new perforator flap for breast reconstruction, with a detailed description of operative technique and four clinical examples. The DFAP flap allows harvest of tissue from the lower buttock and lateral thigh with similar territory to an in-the-crease inferior gluteal artery perforator (IGAP) flap but based on a different perforator. When present, the DFAP is the largest vessel supplying this territory and is often septocutaneous, facilitating dissection when compared with the IGAP flap. We used preoperative imaging with magnetic resonance angiography to assist in accurate flap planning which also permitted precise determination of perforator origin. In patients with either a contraindication to abdominal wall-based perforator flaps or weight distribution below the waist, the DFAP flap provides an alternative to the IGAP flap with an excellent pedicle and a favorable location on the lateral thigh

Prolyl hydroxylase domain 2 (PHD2) has been implicated in several pathways of cell signaling, most notably in its regulation of hypoxia-inducible factor (HIF)-1alpha stability. In normoxia, PHD2 hydroxylates proline residues on HIF-1alpha, rendering it inactive. However, in hypoxia, PHD2 is inactive, HIF-1alpha is stabilized and downstream effectors such as vascular endothelial growth factor and fibroblast growth factor-2 are produced to promote angiogenesis. In the present study we utilize RNA interference to PHD2 to promote therapeutic angiogenesis in a diabetic wound model, presumably by the stabilization of HIF-1alpha. Stented wounds were created on the dorsum of diabetic Lepr db/db mice. Mice were treated with PHD2 small interfering RNA (siRNA) or nonsense siRNA. Wounds were measured photometrically on days 0-28. Wounds were harvested for histology, protein, and RNA analysis. Diabetic wounds treated with siRNA closed within 21+/-1.2 days; sham-treated closed in 28+/-1.5 days. By day 7, Western blot revealed near complete suppression of PHD protein and corresponding increased HIF-1alpha. Angiogenic mediators vascular endothelial growth factor and fibroblast growth factor-2 were elevated, corresponding to increased CD31 staining in the treated groups. siRNA-mediated silencing of PHD2 increases HIF-1alpha and several mediators of angiogenesis. This corresponded to improved time to closure in diabetic wounds compared with sham-treated wounds. These findings suggest that impaired wound healing in diabetes can be ameliorated with therapeutic angiogenesis

Fifty-seven adult patients with facial paralysis, who underwent direct muscle neurotisation, were reviewed and divided into three categories depending on the function that direct neurotisation was aiming to augment. Group 1 included 30 patients who underwent direct neurotisation for eye closure and blink, group 2 consisted of 23 patients for smile augmentation, and group 3 comprised 31 patients for depressor. The age of the patients ranged from 21 to 74 years. Denervation time (Dt) ranged from 8 months to 42 years. Eight patients had partial facial paralysis, and 49 patients had complete facial paralysis. The results were based on the functional and electromyography (EMG) scoring of the neurotised muscles showing an overall EMG mean improvement of 26.56% in eye closure, 34.47% in smile restoration and 32.67% in depressor function by the procedure. Median improvement in all facial functions was one grade (25%) in theTerzis grading systems regarding the respective facial functions. The prerequisites are Dt less than 6 months and a functional contralateral facial nerve. In cases where Dt is more than 27 months and preoperative EMG's are silent, a free or pedicled muscle should be used to substitute the denervated native facial muscle. Promoting expressivity and augmenting facial muscle function using direct muscle neurotisation are important components in facial reanimation

Melanocyte stem cells (McSCs) intimately interact with epithelial stem cells (EpSCs) in the hair follicle bulge and secondary hair germ (sHG). Together, they undergo activation and differentiation to regenerate pigmented hair. However, the mechanisms behind this coordinated stem cell behavior have not been elucidated. Here, we identified Wnt signaling as a key pathway that couples the behavior of the two stem cells. EpSCs and McSCs coordinately activate Wnt signaling at the onset of hair follicle regeneration within the sHG. Using genetic mouse models that specifically target either EpSCs or McSCs, we show that Wnt activation in McSCs drives their differentiation into pigment-producing melanocytes, while EpSC Wnt signaling not only dictates hair follicle formation but also regulates McSC proliferation during hair regeneration. Our data define a role for Wnt signaling in the regulation of McSCs and also illustrate a mechanism for regeneration of complex organs through collaboration between heterotypic stem cell populations. PAPERFLICK:

The proximal interphalangeal joint (PIP) joint is the most crucial joint for the functionality of a finger. For a child with complex injury of the hand every effort should be exercised to maximize function restoration. If the PIP joint is irreparably damaged, its reconstruction is indicated. The technique of autogenic heterotopic vascularized toe joint transplantation provides unique advantage of a composite transfer of skin, tendons, bone and joint alone with growth plate and its efficacy has been affirmed in children. It has been suggested that such transfers require intact flexor tendon to achieve satisfactory results, our experience however indicates quite the contrary. As evidenced by this report of a 7-year-old boy with abrasion and avulsion injury to his dominant right hand resulting in a complex defect with skin lose, extensor, flexor avulsion along with cominution of the PIP joint of his long finger. A surgical formulation of staged reconstruction scheme including an autogenic heterotopic vascularized toe joint transplantation led to complete functional restoration to his right hand. (c) 2011 Wiley-Liss, Inc. Microsurgery 2011

INTRODUCTION: : A cervicofacial flap remains the principal method to close defects of the posterior cheek. Schrudde described a variant of this technique, termed the angle-rotation flap, which allowed primary closure of the donor site. This flap has been elevated in the deep plane for the more medial defects. We extend this technique for upper lip reconstruction. METHODS: : Two cases were reviewed that underwent upper lip reconstruction with the deep-plane Schrudde flap. RESULTS: : Two cases are presented to describe the use of the deep-plane angle-rotation flap. The first patient sustained a burn to his upper lip and the second patient had a partially grafted defect following a Mohs excision. DISCUSSION: : In patients with insignificant nasolabial folds, the deep-plane Schrudde flap is a good option to reconstruct perioral defects. The utilization of the deep plane improves the blood supply and allows improved contour for reconstruction of deeper defects

This study tested the hypothesis that all-ceramic core-veneer system crown reliability is improved by modification of the core design. We modeled a tooth preparation by reducing the height of proximal walls by 1.5 mm and the occlusal surface by 2.0 mm. The CAD-based tooth preparation was replicated and positioned in a dental articulator for core and veneer fabrication. Standard (0.5 mm uniform thickness) and modified (2.5 mm height lingual and proximal cervical areas) core designs were produced, followed by the application of veneer porcelain for a total thickness of 1.5 mm. The crowns were cemented to 30-day-aged composite dies and were either single-load-to-failure or step-stress-accelerated fatigue-tested. Use of level probability plots showed significantly higher reliability for the modified core design group. The fatigue fracture modes were veneer chipping not exposing the core for the standard group, and exposing the veneer core interface for the modified group