Faculty Bibliography

BACKGROUND: Since their first review of microsurgical correction of facial contour deformities in 19 patients with craniofacial malformations, the authors have treated an additional 74 patients (n = 93). The authors review indications, choices, safety, efficacy, complications, and technical refinements. A treatment algorithm is presented. METHODS: A retrospective chart review of all patients who underwent microvascular reconstruction of the face and all patients with craniofacial dysmorphology was performed. Between 1989 and 2004, a total of 93 patients with the following diagnoses were identified: craniofacial microsomia (n = 73), Treacher Collins syndrome (n = 8), and severe orbitofacial cleft (n = 12). All patients underwent microsurgical facial reconstruction with a superficial inferior epigastric, groin, or circumflex scapular flap. Flap revisions, complications, and non-free flap related surgery were reviewed. RESULTS: The mean age at microvascular reconstruction was 11 years (range, 4 to 27 years). Flap choices included the following: superficial inferior epigastric (n = 4), groin (n = 3), and circumflex scapular (n = 105). Seventy-six patients underwent unilateral and 17 patients underwent bilateral (one of 17 simultaneous) reconstructions. Postoperative complications included partial flap loss (n = 1), reexploration (n = 1), hematoma (n = 5), and cellulitis (n = 5). All patients had subjective improvement in facial contour, symmetry, skin tone, and color. Most patients underwent additional non-free flap procedures including mandibular distraction and ear reconstruction. CONCLUSIONS: Microsurgical flaps have markedly improved the authors' ability to restore craniofacial contour in patients with craniofacial malformations. In selected patients, the authors choose primary midface augmentation with free vascularized tissue to restore form and function. Microsurgical flaps in patients with craniofacial malformations are safe, effective, and reliable

BACKGROUND: Endothelial progenitor cells play an important role in neovascularization of ischemic flaps, a process that is significantly impaired in diabetes. This is the first investigation into the effects of flap ischemia on circulating and bone marrow-derived endothelial progenitor cells. Potential mechanisms for impaired vasculogenesis in diabetes are also investigated. METHODS: Circulating and bone marrow-derived endothelial progenitor cells were isolated from wild-type (n = 24) and diabetic mice (n = 24) with ischemic flaps (days 0, 1, 3, and 7). The number and vasculogenic function of primitive and definitive endothelial progenitor cells were determined by fluorescence-activated cell sorting analysis, culture assay, and vasculogenic colony-forming assay. RESULTS: Ischemia mobilized endothelial progenitor cells (25 +/- 0.5 cells per high-power field at day 7 versus 9.0 +/- 0.6 cells per high-power field, p < 0.01) and enhanced the vasculogenic potential of circulating primitive endothelial progenitor cells (23 +/- 3.2 at day 3 versus 14 +/- 0.8, p < 0.01) relative to baseline. In the bone marrow, endothelial progenitor cell number and vasculogenic potential peaked at day 3 (2.1 +/- 0.3 x 10(5) cells versus 1.3 +/- 0.1 x 10(5) cells, p < 0.05; 36 +/- 1.9 versus 27 +/- 1.6, p < 0.05, respectively). In diabetes, circulating endothelial progenitor cell mobilization (5.8 +/- 0.4 cells per high-power field versus 9.0 +/- 0.6 cells per high-power field, p < 0.01) and vasculogenic potential (36 +/- 1.7 versus 43 +/- 2.6, p < 0.05) were impaired relative to the wild-type animals. Bone marrow-derived endothelial progenitor cell number was normal in diabetic animals, but the vasculogenic potential of these cells was significantly impaired (5.7 +/- 0.8 day 1 versus 13.4 +/- 2.5, p < 0.05). CONCLUSIONS: Flap ischemia induces phenotypic changes in bone marrow-derived endothelial progenitor cells that subsequently traffic through the circulation. The vasculogenic potential of endothelial progenitor cells at various stages of differentiation is impaired in diabetes and thus may account for impaired ischemia-induced vasculogenesis observed clinically

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