Faculty Bibliography

BACKGROUND: The study of human autologous fat grafting has been primarily anecdotal. In this study, the authors aim to develop a murine model that recapitulates human fat grafting to study the fate of injected fat and the cell populations contained within. METHODS: The authors' method of fat harvesting and refinement has been described previously. The authors injected nude and tie2/lacZ mice with 2 ml of human lipoaspirate placed on the dorsal surface in a multipass, fan-like pattern. Fatty tissue was injected in small volumes of approximately 1/30 ml per withdrawal. The dorsal skin and associated fat was excised at various time points. Sections were stained with hematoxylin and eosin and cytochrome c oxidase IV. Transgenic tie2/lacZ samples were stained with X-galactosidase. At the 8-week time point, volumetric analysis was performed. RESULTS: Volumetric analysis at the 8-week time point showed 82 percent persistence of the original volume. Gross analysis showed it to be healthy, nonfibrotic, and vascularized. Hematoxylin and eosin analysis showed minimal inflammatory or capsular reaction, with viable adipocytes. Fat grafted areas were vascularized with multiple blood vessels. Cytochrome c oxidase IV human-specific stain and beta-galactosidase expression revealed these vessels to be of human origin. CONCLUSIONS: The authors have developed a murine model with which to study the fate of injected lipoaspirate. There is a high level of persistence of the grafted human fat, with minimal inflammatory reaction. The fat is viable and vascularized, demonstrating human-derived vessels in a mouse model. This model provides a platform for studying the populations of progenitor cells known to reside in lipoaspirate

BACKGROUND: Nasoalveolar molding was developed to improve dentoalveolar, septal, and lower lateral cartilage position before cleft lip repair. Previous studies have documented the long-term maintenance of columella length and nasal dome form and projection. The purpose of the present study was to determine the effect of presurgical nasoalveolar molding on long-term unilateral complete cleft nasal symmetry. METHODS: A retrospective review of 25 consecutively presenting nonsyndromic complete unilateral cleft lip-cleft palate patients was conducted. Fifteen patients were treated with presurgical nasoalveolar molding for 3 months before surgical correction, and 10 patients were treated by surgical correction alone. The average age at the time of follow-up was 9 years. Four nasal anthropometric distances and two angular relationships were measured to assess nasal symmetry. RESULTS: All six measurements demonstrated a greater degree of nasal symmetry in nasoalveolar molding patients compared with the patients treated with surgery alone. Five symmetry measurements were significantly more symmetric in the nasoalveolar molding patients and one measurement demonstrated a nonsignificant but greater degree of symmetry compared with the patients treated with surgery alone. CONCLUSIONS: The data demonstrate that the lower lateral and septal cartilages are more symmetric in the nasoalveolar molding patients compared with the surgery-alone patients. Furthermore, the improved symmetry observed in nasoalveolar molding-treated noses during the time of the primary surgery is maintained at 9 years of age

BACKGROUND: Despite technical advancement, treatment of congenital alveolar clefts has remained controversial. Currently, primary alveolar cleft repair (i.e., gingivoperiosteoplasty) has a 41 to 73 percent success rate. However, the remaining patients have persistent alveolar bone defects requiring secondary grafting procedures. Morbidity of secondary procedures includes pain, graft resorption, extrusion or infection, and graft or tooth loss. The authors present a novel rat alveolar defect model designed to facilitate investigation of therapeutics aimed at improving bone formation following primary alveolar cleft repair in humans. METHODS: Sixteen 8-week-old Sprague-Dawley rats underwent creation of a 7 x 4 x 3-mm complete alveolar defect from the maxillary incisors to the zygomatic arch. Four animals were humanely killed at each of the following time points: 0, 4, 8, and 12 weeks. Morphometric analysis of the alveolar defect was determined by means of micro-computed tomography and histology. RESULTS: Micro-computed tomography demonstrated that new bone filled 43 +/- 5.6 percent of the alveolar defect at 4 weeks, 53 +/- 8.3 percent at 8 weeks, and 48 +/- 3.5 percent at 12 weeks. Histologically, at 4 weeks, proliferating fibroblasts and polymorphonuclear cells were scattered throughout the disorganized collagen in the intercalary gap. By 8 weeks, nascent woven bone spicules extended from the edges of the defect. At 12 weeks, the woven spicules had remodeled, with scant additional bone deposition. CONCLUSION: This model creates a critical-size alveolar defect that is similar in size and location to human alveolar defects and is suitable for studying proposed therapeutics.

Large acquired intracranial defects can result from trauma or surgery. When reoperation is required because of infection or tumor recurrence, management of the intracranial dead space can be challenging. By providing well-vascularized bulky tissue, intracranial microvascular free flaps offer potential solutions to these life-threatening complications. A multi-institutional retrospective chart and radiographic review was performed of all patients who underwent microvascular free-flap surgery for salvage treatment of postoperative intracranial infections between 1998 and 2006. A total of six patients were identified with large intracranial defects and postoperative intracranial infections. Four patients had parenchymal resections for tumor or seizure and two patients had posttraumatic encephalomalacia. All patients underwent operative debridement and intracranial free-flap reconstruction using the latissimus dorsi muscle ( N = 2), rectus abdominis muscle ( N = 2), or omentum ( N = 2). All patients had titanium ( N = 4) or Medpor ( N = 2) cranioplasties. We concluded that surgery or trauma can result in significant intracranial dead space. Treatment of postoperative intracranial infection can be challenging. Vascularized free tissue transfer not only fills the void, but also provides a delivery system for immune cells, antibodies, and systemically administered antibiotics. The early use of this technique when intracranial dead space and infection coexist is beneficial

BACKGROUND: This article aims to assess the spectrum of unfavorable events or incidents encountered during mandibular distraction and to evaluate the difference in the incident rates among the following treatment groups: (1) native bone distraction using an external device, (2) native bone distraction using an internal device, and (3) grafted bone distraction using an external device. METHODS: This retrospective study examined the records of 141 patients treated by mandibular distraction over a 16-year period. Of the total 141 patients, 56 underwent unilateral mandibular distraction and 85 underwent bilateral mandibular distraction, contributing to a total of 226 sided distraction procedures. The number of procedures performed on native bone using external devices was 149, versus 41 internal devices. There were 36 distractions performed on grafted bone with external devices. Incidents were broadly classified into three groups based on a severity index. A minor incident was one that resolved satisfactorily with minimal or no invasive intervention. A moderate incident was one that resolved satisfactorily with moderate clinical intervention. A major incident was one that did not resolve or could not be resolved with surgical intervention, and compromised treatment outcome. RESULTS: The major incident rate was 5.31 percent (total of 226 distraction procedures). A higher rate of major incidents was observed when distracting grafted bone. The overall minor incident rate was 26.99 percent and the moderate incident rate was 20.35 percent. CONCLUSION: Mandibular distraction can be considered a safe and predictable procedure for lengthening/augmenting the mandible in patients with lower jaw deficiencies

BACKGROUND: Bone engineering requires thicker three-dimensional constructs than the maximum thickness supported by standard cell-culture techniques (2 mm). A flow-perfusion bioreactor was developed to provide chemotransportation to thick (6 mm) scaffolds. METHODS: Polyurethane scaffolds, seeded with murine preosteoblasts, were loaded into a novel bioreactor. Control scaffolds remained in static culture. Samples were harvested at days 2, 4, 6, and 8 and analyzed for cellular distribution, viability, metabolic activity, and density at the periphery and core. RESULTS: By day 8, static scaffolds had a periphery cell density of 67% +/- 5.0%, while in the core it was 0.3% +/- 0.3%. Flow-perfused scaffolds demonstrated peripheral cell density of 94% +/- 8.3% and core density of 76% +/- 3.1% at day 8. CONCLUSIONS: Flow perfusion provides chemotransportation to thick scaffolds. This system may permit high throughput study of 3D tissues in vitro and enable prefabrication of biological constructs large enough to solve clinical problems

BACKGROUND: Impaired diabetic wound healing is due, in part, to defects in mesenchymal progenitor cell tracking. Theoretically, these defects may be overcome by administering purified progenitor cells directly to the diabetic wound. The authors hypothesize that these progenitor cells will differentiate into endothelial cells, increase wound vascularity, and improve wound healing. METHODS: Lineage-negative progenitor cells were isolated from wild-type murine bone marrow by magnetic cell sorting, suspended in a collagen matrix, and applied topically to full-thickness excisional dorsal cutaneous wounds in diabetic mice. Application of lineage-positive hematopoietic cells or acellular collagen matrix served as comparative controls (n = 16 for each group; n = 48 total). Time to closure and percentage closure were calculated by morphometry. Wounds were harvested at 7, 14, 21, and 28 days and then processed, sectioned, stained (lectin/DiI and CD31), and vascularity was quantified. RESULTS:: Wounds treated with lineage-negative cells demonstrated a significantly decreased time to closure (14 days) compared with lineage-positive (21 days, p = 0.013) and collagen controls (28 days, p = 0.004), and a significant improvement in percentage closure at 14 days compared with the lineage-positive group (p < 0.01) and the collagen control (p < 0.01). Fluorescently tagged lineage-negative cells remained viable in the wound for 28 days, whereas lineage-positive cells were not present after 7 days. Lineage-negative, but not lineage-positive, cells differentiated into endothelial cells. Vascular density and vessel cross-sectional area were significantly higher in lineage-negative wounds. CONCLUSION: Topical progenitor-cell therapy successfully accelerates diabetic wound closure and improves wound vascularity