Faculty Bibliography

BACKGROUND: Although the condition is rare, some children are born with cervical clefts or masses that require repair during infancy. The scarring in the submental region can tether the developing mandible at the menton, producing a developmental microgenia or 'tethered chin.' METHODS: A retrospective review of the senior author's (B.M.Z.) patient records was performed; three cases of tethered chin were identified. In each case, a staged surgical approach was used. RESULTS: In two cases, previous unsuccessful surgery complicated the initial presentation. In all cases, the underlying soft-tissue anomalies were addressed and the microgenia was corrected. Satisfactory aesthetic and functional results were obtained. CONCLUSIONS: The tethered chin represents a rare entity. Correction of the tethered chin requires a comprehensive understanding of the underlying abnormality and an appreciation of the multiple factors that contribute to chin function and aesthetics

BACKGROUND: Patients with craniofacial anomalies can have hard and soft tissue deficiencies. In some cases, distraction osteogenesis can restore the bony deficiencies, but the soft tissue contour defect remains problematic. For these patients, the union of distraction osteogenesis and microvascular free flaps (MVFF) can restore bone and soft tissue form and function. PATIENTS AND METHODS: A retrospective review of all patients treated with mandibular distraction osteogenesis between 1989 and 2005 was performed. A similar review of all patients treated with MVFFs was performed. These 2 cohorts were cross-referenced to identify all patients treated with both procedures. The indications, choices, safety, and efficacy of MVFF reconstruction of facial soft tissues following mandibular reconstruction are reviewed. RESULTS: Over a 16-year period, 141 patients underwent mandibular distraction osteogenesis; 8 patients treated with mandibular distraction osteogenesis subsequently underwent 12 MVFFs. Patient diagnoses included unilateral craniofacial microsomia (n = 2), bilateral craniofacial microsomia (n = 3), Goldenhar syndrome (n = 1), Nager syndrome (n = 1), and Treacher-Collins syndrome (n = 1). Free flap choices included 10 parascapular fasciocutaneous, 1 parascapular osteofasciocutaneous, and 1 fibular osteocutaneous flap. Four patients underwent staged bilateral free flaps. A single case of partial flap loss was the only complication. In all cases, facial contour was improved following MVFF transfer. CONCLUSIONS: In certain circumstances, facial rehabilitation may require the marriage of craniofacial and microsurgical techniques to restore both form and function. In these cases, mandibular distraction osteogenesis and MVFFs can be safely and effectively combined

A 60-year-old male with lumbosacral multiple myeloma received 5100 cGy of external-beam radiation, thalidomide, and Decadron. He subsequently underwent excision of the epidural tumor, decompressive L4, L5, and S1 laminectomies, and bilateral L4-5 and L5-S1 medial facetectomies. The patient developed osteoradionecrosis, cerebrospinal fluid leak, wound infection, and sepsis. Debridement and bilateral V-Y fasciocutaneous advancement flaps failed. Pedicled omental transposition flap through a Petit triangle tunnel was successfully performed. Omental transposition provides a safe option for salvage treatment of irradiated, infected lumbosacral wounds. The plastic and trophic qualities of the omentum make it an excellent choice to fill poorly vascularized wounds. In addition to its immunologic and neoangiogenic properties, the omentum has a dense lymphatic network with tremendous absorptive potential. Its biologic advantages must be weighed against the need for celiotomy and available local options according to circumstances

To shorten the reconstructive process, improve results, and provide additional options for women seeking mastectomy, we used an acellular cryopreserved dermal matrix (AlloDerm) sling to reestablish the lower pole of the pectoralis major muscle. This technique creates a subpectoral-sub-AlloDerm pocket that completely encloses the breast implant. By tailoring the width of the AlloDerm, we can precisely control the degree of lower-pole fullness. This technique shortens or eliminates the need for tissue expansion and provides an additional option for single-stage breast reconstruction with implants. We have selectively used this technique as a reconstructive option for 10 women undergoing bilateral mastectomy (20 breasts)

Although many theories have attempted to explain the etiopathogenesis of premature cranial suture fusion, which results in craniosynostosis, recent studies have focused on the role of growth factors and receptors. Using a well-established model of cranial suture biology, the authors developed a novel approach to quantitatively analyze the gene expression profiles of candidate cranial suture growth factors and their receptors. We collected suture mesenchyme and adjacent osteogenic fronts from Sprague-Dawley rats at postnatal days 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 35. RNA was extracted from posterior frontal (PF) and sagittal (SAG) sutures, and reverse transcription-polymerase chain reaction (RT-PCR) was performed for cranial suture candidate cytokines BMP2, BMP3, BMP4, FGF-2, FGFR1, FGFR2, FGFR4, TGF-betaRI, TGF-betaRII, and TGF-betaRIII. The authors confirmed quantitative RT-PCR results with Southern and dot blot analyses. Suture growth factor and receptor expression levels changed significantly with time. Expression levels decreased toward baseline in the SAG suture by day 35. There was a marked difference in FGFR1, FGF-2, TGF-betaRI, and TGF-betaRII expression levels when comparing the fusing PF and nonfusing SAG sutures. Although FGF-2 ligand expression was low, FGF receptor 1 (FGFR1) levels were markedly elevated with a bimodal expression pattern in both PF and SAG similar to that of BMP2, BMP3, and BMP4. Although there were statistically significant differences in TGF-betaRI and TGF-betaRII expression in the PF and SAG sutures, TGF-betaRIII levels were unchanged. The authors report a novel approach to cranial suture growth factor/receptor profiling and confirm their results with standard analytic tools. The data confirm, quantify, and extend the results of previously published studies. By quantifying the gene expression profiles of normal cranial suture biology, we may begin to understand the aberrant growth factor cascades of craniosynostosis and devise targeted therapeutic interventions that can alter the course of this malady

An abundance of genetic and experimental data have suggested that fibroblast growth factor (FGF) signaling plays a central role in physiological and pathological cranial suture fusion. Although alterations in the differentiation and proliferation of sutural osteoblasts may be a key mediator of this process, the mechanisms by which FGF signaling regulates osteoblast differentiation remain incompletely understood. In the current study, the authors show that recombinant human FGF-2 alters osteoblastic expression of bone morphogenetic protein-2 and Msx-2 in vitro to favor cellular differentiation and osteoinduction. The ERK1/2 intracellular signaling cascade was shown to be necessary for recombinant human FGF-2-mediated bone morphogenetic protein-2 transcriptional changes. Furthermore, the cellular production of an intermediate transcriptional modifier was found to be necessary for the recombinant human FGF-2-mediated gene expression changes in bone morphogenetic protein-2 and Msx-2. Together, these findings offer new insight into the mechanisms by which FGF-2 modulates osteoblast biology

Three-dimensional finite element (FE) analyses were performed to characterize the local mechanical environment created within the tissue regenerate during mandibular distraction osteogenesis (DO) in a rat model. Finite element models were created from three-dimensional computed tomography image data of rat hemi-mandibles at four different time points during an optimal distraction osteogenesis protocol (i.e., most successful protocol for bone formation): end latency (post-operative day (POD) 5), distraction day 2 (POD 7), distraction day 5 (POD 10), and distraction day 8 (POD 13). A 0.25 mm distraction was simulated and the resulting hydrostatic stresses and maximum principal tensile strains were determined within the tissue regenerate. When compared to previous histological findings, finite element analyses showed that tensile strains up to 13% corresponded to regions of new bone formation and regions of periosteal hydrostatic pressure with magnitudes less than 17 kPa corresponded to locations of cartilage formation. Tensile strains within the center of the gap were much higher, leading us to conclude that tissue damage would occur there if the tissue was not compliant enough to withstand such high strains, and that this damage would trigger formation of new mesenchymal tissue. These data were consistent with histological evidence showing mesenchymal tissue present in the center of the gap throughout distraction. Finite element analyses performed at different time points during distraction were instrumental in determining the changes in hydrostatic stress and tensile strain fields throughout distraction, providing a mechanical environment rationale for the different levels of bone formation in end latency, and distraction day 2, 5, and 8 specimens

Craniosynostosis, the premature fusion of cranial sutures, is one of the most common craniofacial anomalies, with a reported incidence of up to one in 2500 live births. Despite its prevalence, the cause of craniosynostosis remains unknown. Previously, apoptosis has been postulated to be a contributing factor in the pathogenesis of craniosynostosis, although the role of programmed cell death in cranial sutures is poorly understood. To address this problem, the authors used an established rodent model of posterior-frontal suture fusion and sagittal suture patency to globally examine apoptosis in cranial sutures. Apoptosis was evaluated by systemically coinjecting Sprague-Dawley rats with both fluorescent and technetium-99m-labeled annexin V at time points before, during, and after the period of predicted posterior-frontal suture fusion to determine the magnitude and time course of overall apoptotic activity in both fusing and patent sutures. Using these novel in situ imaging techniques, the authors observed a significant increase in the overall levels of apoptosis in both the posterior-frontal and sagittal suture complexes during the period of predicted posterior-frontal suture fusion. To further explore this increase in apoptotic activity, they used microarray technology to study apoptosis-related genes within the suture complex. Interestingly, there was activation of distinct apoptotic pathways in the posterior-frontal and sagittal sutures during the period of predicted posterior-frontal suture fusion. Whereas increased transcription of genes associated with the mitochondria-mediated apoptotic pathway occurred in the posterior-frontal suture during fusion, activation of genes associated with the death receptor-mediated apoptotic pathway predominated in the patent sagittal suture during the same time period. These data suggest that although overall apoptotic activity in rat patent and fusing sutures is similar, the pathways mediating apoptosis within each suture are distinct

While the histological and ultrastructural changes associated with distraction osteogenesis have been extensively characterized using various animal models, the molecular mechanisms governing this technique remain poorly understood. In the current study, for the first time, we describe a mouse mandibular distraction osteogenesis model. Development of this model will allow assessment of factors involved in normal vs. abnormal healing (especially in non-unions) of craniofacial skeletal elements. Complete osteotomies were created on the right hemimandibles of 51 adult male CD-1 mice and customized distraction devices attached. Thirty-three animals underwent gradual distraction (5 days latency, distraction at 0.2 mm BID x 8 days, 28 days consolidation), while the remaining 18 mice underwent acute lengthening (immediate distraction to 3.2 mm) at the time of surgery. Mandibles were harvested at time points corresponding to the latent (POD 5), distraction (POD 9, 13), and consolidation (POD 28, 41) periods and processed for histological or quantitative real-time RT-PCR analysis. Specimens from each group were processed for microCT analysis. Histological and radiological data demonstrated that all mandibles undergoing gradual distraction achieved complete bony union by the end of consolidation, while those undergoing acute lengthening formed a fibrous non-union. Quantitative real-time RT-PCR demonstrated upregulation of mRNA for VEGF, FGF-2, collagen I, and osteopontin during gradual distraction but not during acute lengthening. These data validate our novel mouse mandibular distraction model and demonstrate its utility in elucidating the molecular mechanisms regulating bone formation during distraction osteogenesis as compared to those that are expressed during the formation of fibrous non-unions