Faculty Bibliography

ABSTRACT: The goal of this article was to illustrate the ease in which virtual surgery and computer-aided design and manufacturing can be used by the craniomaxillofacial surgeon to create tremendously accurate postoperative results and provide confidence with even the most complex three-dimensional bony reconstructions. With advancements in software technology and three-dimensional printing, our ability to plan and execute precise bony reconstruction has become a reality. With this technology, guides can be made to ensure exact bony repositioning or replacement. These guides can help guide cutting of the bone and can act as splints to precisely reposition the bone and direct plate placement. With use of these computer-aided design and manufacturing guides and the addition of guidance technology, the position of the bone can be guaranteed intraoperatively. We review our unique and advanced method in approaching some of these problems and illustrate the application of these techniques in mandibular reconstruction, orthognathic surgery, maxillofacial trauma, and temporomandibular joint reconstruction. This technology continues to evolve, and our indications for its application continue to grow. This article represents only a small portion of the types of cases in which these techniques have already been applied.

BACKGROUND: Fat grafting has been shown clinically to improve the quality of burn scars. To date, no study has explored the mechanism of this effect. We aimed to do so by combining our murine model of fat grafting with a previously described murine model of thermal injury. METHODS: Wild-type FVB mice (n=20) were anaesthetised, shaved and depilitated. Brass rods were heated to 100 degrees C in a hot water bath before being applied to the dorsum of the mice for 10s, yielding a full-thickness injury. Following a 2-week recovery period, the mice underwent Doppler scanning before being fat/sham grafted with 1.5cc of human fat/saline. Half were sacrificed 4 weeks following grafting, and half were sacrificed 8 weeks following grafting. Both groups underwent repeat Doppler scanning immediately prior to sacrifice. Burn scar samples were taken following sacrifice at both time points for protein quantification, CD31 staining and Picrosirius red staining. RESULTS: Doppler scanning demonstrated significantly greater flux in fat-grafted animals than saline-grafted animals at 4 weeks (fat=305+/-15.77mV, saline=242+/-15.83mV; p=0.026). Enzyme-linked immunosorbent assay (ELISA) analysis in fat-grafted animals demonstrated significant increase in vasculogenic proteins at 4 weeks (vascular endothelial growth factor (VEGF): fat=74.3+/-4.39ngml(-1), saline=34.3+/-5.23ngml(-1); p=0.004) (stromal cell-derived factor-1 (SDF-1): fat=51.8+/-1.23ngml(-1), saline grafted=10.2+/-3.22ngml(-1); p<0.001) and significant decreases in fibrotic markers at 8 weeks (transforming growth factor-ss1(TGF-ss): saline=9.30+/-0.93, fat=4.63+/-0.38ngml(-1); p=0.002) (matrix metallopeptidase 9 (MMP9): saline=13.05+/-1.21ngml(-1), fat=6.83+/-1.39ngml(-1); p=0.010). CD31 staining demonstrated significantly up-regulated vascularity at 4 weeks in fat-grafted animals (fat=30.8+/-3.39 vessels per high power field (hpf), saline=20.0+/-0.91 vessels per high power field (hpf); p=0.029). Sirius red staining demonstrated significantly reduced scar index in fat-grafted animals at 8 weeks (fat=0.69+/-0.10, saline=2.03+/-0.53; p=0.046). CONCLUSIONS: Fat grafting resulted in more rapid revascularisation at the burn site as measured by laser Doppler flow, CD31 staining and chemical markers of angiogenesis. In turn, this resulted in decreased fibrosis as measured by Sirius red staining and chemical markers

BACKGROUND: Although different cranioplasty storage methods are currently in use, no study has prospectively compared these methods. The authors compare freezing and subcutaneous storage methods in a rat model. METHODS: Trephine defects (10 mm) were created in 45 Sprague-Dawley rats. The cranial bone grafts were stored in an autologous subcutaneous pocket (n = 15), frozen at -80 degrees C (n = 15), immediately analyzed (n = 12), or immediately replanted into the defect (n = 3). After 10 days of storage, the subcutaneous or frozen grafts were either replanted (subcutaneous, n = 3; frozen, n = 3) or analyzed (subcutaneous, n = 12; frozen, n = 12). Grafts underwent histologic analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, alkaline phosphatase assay, mechanical testing, and micro-computed tomographic imaging. RESULTS: After 10 days of storage, physiologic assays demonstrated a significant decrease in cellular functionality (e.g., alkaline phosphatase assay concentration: fresh, 18.8 +/- 0.77 mM/mg; subcutaneous, 12.2 +/- 0.63 mM/mg; frozen, 8.07 +/- 1.1 mM/mg; p < 0.012 for all comparisons). Mechanical integrity (maximal load) of fresh grafts was greatest (fresh, 9.26 +/- 0.29 N; subcutaneous, 6.27 +/- 0.64 N; frozen, 4.65 +/- 0.29 N; fresh compared with frozen, p < 0.001; fresh compared with subcutaneous, p = 0.006). Replantation of subcutaneously stored and frozen grafts resulted in limited bony union and considerable resorption after 12 weeks; in contrast, replanted fresh grafts demonstrated bony union and little resorption. CONCLUSIONS: Current preservation methods for interval cranioplasty do not maintain bone graft viability. Subcutaneous storage appears to provide a small advantage compared with freezing.

BACKGROUND: : Distraction osteogenesis has revolutionized the treatment of craniofacial deformities, but it is limited by lengthy consolidation periods and tenuous healing in certain clinical settings, such as irradiated tissue. In this study, the authors aim to investigate whether increasing neovascularization by progenitor cell mobilization accelerates bone formation during distraction. METHODS: : Sprague-Dawley rats aged 8 weeks (n = 36) were subjected to unilateral mandibular distraction with 3-day latency, 7-day activation (0.25 mm twice daily), and 21-day consolidation periods. From the beginning of the consolidation period, animals received daily injections of either AMD3100 (bone marrow progenitor cell mobilizing agent) or sterile saline. Animals were euthanized on postoperative day 31; mandibles were harvested; and bone regeneration was assessed using micro-computed tomography, immunohistochemistry, bone morphogenetic protein-2 enzyme-linked immunosorbent assay, and mechanical testing. RESULTS: : Immunohistochemistry demonstrated that AMD3100 treatment increased vascular density and bone formation. Micro-computed tomography and dual-emission x-ray absorptiometry demonstrated that AMD3100-treated animals had improved bone generation compared with sham-treated controls. Greater force was required on three-point testing to break AMD3100-treated bone. Bone morphogenetic protein-2 expression was up-regulated with AMD3100. Interestingly, the nondistracted contralateral hemimandibles treated with AMD3100 were also stronger than sham-treated counterparts. CONCLUSIONS: : Progenitor cell mobilization improves bone regeneration in a rat distraction model. Furthermore, because this effect is seen in healthy bone and in ischemic bone healing during distraction, the mechanism is not merely related to oxygenation, but could be a phenomenon of fluid flow

BACKGROUND: : Although bone repair is a relatively efficient process, a significant portion of patients fail to heal their fractures. Because adequate blood supply is essential to osteogenesis, the authors hypothesize that augmenting neovascularization by increasing the number of circulating progenitor cells will improve bony healing. METHODS: : Bilateral full-thickness defects were created in the parietal bones of C57 wild-type mice. Intraperitoneal AMD3100 (n = 33) or sterile saline (n = 33) was administered daily beginning on postoperative day 3 and continuing through day 18. Circulating progenitor cell number was quantified by fluorescence-activated cell sorting. Bone regeneration was assessed with micro-computed tomography. Immunofluorescent CD31 and osteocalcin staining was performed to assess for vascularity and osteoblast density. RESULTS: : AMD3100 treatment increased circulating progenitor cell levels and significantly improved bone regeneration. Calvarial defects of AMD3100-treated mice demonstrated increased vascularity and osteoblast density. CONCLUSIONS: : Improved bone regeneration in this model was associated with elevated circulating progenitor cell number and subsequently improved neovascularization and osteogenesis. These findings highlight the importance of circulating progenitor cells in bone healing and may provide a novel therapy for bone regeneration

Cases in subdisciplines of craniomaxillofacial surgery-corrective jaw surgery, maxillofacial trauma, temporomandibular joint/skull base, jaw reconstruction, and postablative reconstruction-illustrate the ease of use, cost effectiveness, and superior results that can be achieved when using computer-assisted design and 3D volumetric analysis in preoperative surgical planning. This article discusses the materials and methods needed to plan cases, illustrates implementation of guides and implants, and describes postoperative analysis in relation to the virtually planned surgery

Traumatic craniofacial injuries often present as difficult reconstructive challenges for maxillofacial surgeons. Reconstruction is often complicated by significant soft tissue loss, comminuted bony fragments, a tenuous blood supply, and wound contamination. For panfacial injuries, restoration of normal facial width, facial height, and sagittal projection may be difficult to achieve. Marked swelling may limit the surgeons' ability to palpate and recognize subtle bony defects and malunion. Furthermore, a true 3-dimensional assessment of bony alignment may not be possible with traditional surgical exposures to the craniofacial skeleton. This article builds on previous work that introduced the use of 3-dimensionally guided surgery for microvascular free-flap reconstruction of the craniofacial skeleton. Use of this technology improves the planning, timing, and overall precision of microvascular reconstructive surgery. Based on this experience, a similar approach to reconstructing patients with significant craniofacial trauma has been adopted

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