Faculty Bibliography

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

The inflammatory response to ionizing radiation (IR) includes a proangiogenic effect that could be counterproductive in cancer but can be exploited for treating impaired wound healing. We demonstrate for the first time that IR stimulates hypoxia-inducible factor-1alpha (HIF-1alpha) up-regulation in endothelial cells (ECs), a HIF-1alpha-independent up-regulation of stromal cell-derived factor-1 (SDF-1), as well as endothelial migration, all of which are essential for angiogenesis. 5 Gray IR-induced EC HIF-1alpha and SDF-1 expression was greater when combined with hypoxia suggesting an additive effect. While small interfering RNA silencing of HIF-1alpha mRNA and abolition of HIF-1alpha protein induction down-regulated SDF-1 induction by hypoxia alone, it had little effect on SDF-1 induction by IR, demonstrating an independent pathway. SDF-1-mediated EC migration in hypoxic and/or radiation-treated media showed IR induced strong SDF-1-dependent migration of ECs, augmented by hypoxia. IR activates a novel pathway stimulating EC migration directly through the expression of SDF-1 independent of HIF-1alpha induction. These observations might be exploited for stimulation of wound healing or controlling tumor angiogenesis

Diabetes is characterized by several poorly understood phenomena including dysfunctional wound healing and impaired vasculogenesis. p53, a master cell cycle regulator, is upregulated in diabetic wounds and has recently been shown to play a regulatory roles in vasculogenic pathways. We have previously described a novel method to topically silence target genes in a wound bed with small interfering (si)RNA. We hypothesized that silencing p53 results in improved diabetic wound healing and augmentation of vasculogenic mediators. Paired 4-mm stented wounds were created on diabetic db/db mice. Topically applied p53 siRNA, evenly distributed in an agarose matrix, was applied to wounds at postwound day 1 and 7 (matrix alone and nonsense siRNA served as controls). Animals were sacrificed at postwound days 10 and 24. Wound time to closure was photometrically assessed, and wounds were harvested for histology, immunohistochemistry, and immunofluorescence. Vasculogenic cytokine expression was evaluated via Western blot, reverse transcription-polymerase chain reaction, and enzyme-linked immunosorbent assay. The ANOVA/t-test was used to determine significance (p</= 0.05). Local p53 silencing resulted in faster wound healing with wound closure at 18+/-1.3 d in the treated group vs. 28+/-1.0 d in controls. The treated group demonstrated improved wound architecture at each time point while demonstrating near-complete local p53 knockdown. Moreover, treated wounds showed a 1.92-fold increase in CD31 endothelial cell staining over controls. Western blot analysis confirmed near-complete p53 knockdown in treated wounds. At day 10, VEGF secretion (enzyme-linked immunosorbent assay) was significantly increased in treated wounds (109.3+/-13.9 pg/mL) vs. controls (33.0+/-3.8 pg/mL) while reverse transcription-polymerase chain reaction demonstrated a 1.86-fold increase in SDF-1 expression in treated wounds vs. controls. This profile was reversed after the treated wounds healed and before closure of controls (day 24). Augmented vasculogenic cytokine profile and endothelial cell markers are associated with improved diabetic wound healing in topical gene therapy with p53 siRNA

Great variability exists in microsurgical postoperative care in the United States. Lack of standardized postoperative monitoring protocols and appropriate training of monitoring personnel leads to inefficiency and increased cost of providing microsurgical postoperative care. A 45-question survey was sent to all plastic surgery and plastic surgery-based microsurgery program directors in the United States. Questions focused on the number and type of flaps performed, length of stay, complications, postoperative monitoring setting, training provided to monitoring personnel, and limitations in flap monitoring. The response rate was 31% with 3407 microvascular free flaps performed annually at 26 centers. A total of 1533 flaps were monitored in the intensive care unit (ICU) for an average of 3.1 days. In 45% of responding centers patients were cared for in an ICU secondary to a lack of adequately trained nurses at alternative sites. Printed postoperative protocols were provided to nurses in 39% of centers. With a comparative increase cost of $2878 to $3345 per day for ICU care, this translates into an annual increased cost of $13.7 to $15.9 million to the responding centers. Improved nursing training and the use of standardized postoperative protocols may allow patients to be monitored in non-ICU settings postoperatively, thereby reducing the costs associated with providing postoperative microsurgical care

When free tissue transfer is employed for defects of the lower third of the leg, recipient anastomoses are typically performed to major vessels. The aim of this study was to assess soleal perforators located in the distal half of the leg as potential vessels for free flap recipient vessels. Six fresh cadavers (12 limbs) were dissected. Perforators of adequate size (>or=1 mm) were documented as was the location and ease of dissection. Lower extremity magnetic resonance angiograms (MRAs) of 18 extremities were retrospectively reviewed. Two free tissue transfers to lower extremity perforators were presented. Soleal perforators most reliably matched our recipient vessel requirements. Perforators were of adequate size to support free tissue transfer, easy to dissect, and were located at mid/distal fibula level. MRA evaluation confirmed these results. One free tissue reconstruction was performed for trauma (posterior tibial perforator) and one was performed for a chronic radiation wound (peroneal perforator). The soleus muscle is easily exposed and is supplied distally by perforators from both the posterior tibial and the peroneal artery systems. These perforating branches are more accessible than the major lower extremity arteries, making the exposure and anastomosis technically easier and sparing potential iatrogenic injury to critical vessels

Medicinal leeches are used to control venous congestion. Aeromonas in the leech gut are essential for digestion of blood. This case report describes a patient who had Aeromonas bacteremia develop after leeching. He had an injury to his hand that required replantation of his thumb. Following the surgery, leech therapy was started with ampicillin-sulbactam prophylaxis. Sepsis developed. Blood cultures were positive for Aeromonas that were resistant to ampicillin-sulbactam. The antibiotic was changed to ciprofloxacin on the basis of the sensitivity profile of the organisms. Cultures from the leech bathwater confirmed it as the source of the Aeromonas. Clinicians who use leech therapy must be aware that leeches can harbor Aeromonas species resistant to accepted prophylactic antibiotics and that sepsis may occur

OBJECTIVE: Progenitor cells (PCs) contribute to postnatal neovascularization and tissue repair. Here, we explore the mechanism contributing to decreased diabetic circulating PC number and propose a novel treatment to restore circulating PC number, peripheral neovascularization, and tissue healing. RESEARCH DESIGN AND METHODS: Cutaneous wounds were created on wild-type (C57BL/J6) and diabetic (Lepr(db/db)) mice. Blood and bone marrow PCs were collected at multiple time points. RESULTS: Significantly delayed wound closure in diabetic animals was associated with diminished circulating PC number (1.9-fold increase vs. 7.6-fold increase in lin(-)/sca-1(+)/ckit(+) in wild-type mice; P < 0.01), despite adequate numbers of PCs in the bone marrow at baseline (14.4 +/- 3.2% lin(-)/ckit(+)/sca1(+) vs. 13.5 +/- 2.8% in wild-type). Normal bone marrow PC mobilization in response to peripheral wounding occurred after a necessary switch in bone marrow stromal cell-derived factor-1alpha (SDF-1alpha) expression (40% reduction, P < 0.01). In contrast, a failed switch mechanism in diabetic bone marrow SDF-1alpha expression (2.8% reduction) resulted in impaired PC mobilization. Restoring the bone marrow SDF-1alpha switch (54% reduction, P < 0.01) with plerixafor (Mozobil, formerly known as AMD3100) increased circulating diabetic PC numbers (6.8 +/- 2.0-fold increase in lin(-)/ckit(+), P < 0.05) and significantly improved diabetic wound closure compared with sham-treated controls (32.9 +/- 5.0% vs. 11.9 +/- 3% at day 7, P > 0.05; 73.0 +/- 6.4% vs. 36.5 +/- 7% at day 14, P < 0.05; and 88.0 +/- 5.7% vs. 66.7 +/- 5% at day 21, P > 0.05, respectively). CONCLUSIONS: Successful ischemia-induced bone marrow PC mobilization is mediated by a switch in bone marrow SDF-1alpha levels. In diabetes, this switch fails to occur. Plerixafor represents a potential therapeutic agent for improving ischemia-mediated pathology associated with diabetes by reducing bone marrow SDF-1alpha, restoring normal PC mobilization and tissue healing