Faculty Bibliography

PURPOSE:: To investigate the bone regenerative effect of polymer and collagen incorporation to synthetic bone graft materials. MATERIALS AND METHODS:: The bone ingrowth of biphasic graft materials was tested in a rabbit calvaria defect model after chemical characterization: HA/TCP (25%/75%) with collagen, HA/TCP (25%/75%) without collagen, (HA/TCP)/PLGA (85%/15%) with collagen, (HA/TCP)/PLGA (65%/35%) with collagen and a commercially available (HA/TCP)/PLGA (50%/50%) was used as control. After 4 and 8 weeks, the retrieved samples were subjected to histomorphometrical analysis. RESULTS:: Histomorphometry presented no significant differences concerning the bone formation between the different groups at both 4 and 8 weeks. Evidently, the (HA/TCP)/PLGA (65%/35%) with collagen presented the least amount of soft tissue incorporation within the defect. The same group possessed higher amounts of bone graft material within the defect throughout the 8-week observation period, whereas the other groups seemed to decrease in volume from 4 to 8 weeks. CONCLUSION:: Increase of the PLGA percentage within the biphasic graft material seemed to maintain its volume and prevented soft tissue migration, which could be clinically beneficial.

Introduction: Lymphedema, a common complication of cancer treatment, is characterized by inflammation, fibrosis, and adipose deposition. We previously have shown that macrophage infiltration is increased in mouse models of lymphedema. Because macrophages are regulators of lymphangiogenesis and fibrosis, this study aimed to determine the role of these cells in lymphedema using depletion experiments. Methods: Matched biopsy specimens of normal and lymphedema tissues were obtained from patients with unilateral upper extremity breast cancer-related lymphedema and macrophage accumulation was assessed using immunohistochemistry. In addition, we used a mouse tail model of lymphedema to quantify macrophage accumulation and analyze outcomes of conditional macrophage depletion. Results: Histological analysis of clinical lymphedema biopsies revealed significantly increased macrophage infiltration. Similarly, in the mouse tail model, lymphatic injury increased the number of macrophages and favored M2 differentiation. Chronic macrophage depletion using lethally irradiated wild-type mice reconstituted with CD11b-DTR mouse bone marrow did not decrease swelling, adipose deposition, or overall inflammation. Macrophage depletion after lymphedema had become established significantly increased fibrosis, accumulation of CD4+ cells, and promoted Th2 differentiation while decreasing lymphatic transport capacity and VEGF-C expression. Conclusion: Our findings suggest that macrophages home to lymphedematous tissues and differentiate into the M2 phenotype. In addition, our findings suggest that macrophages have an anti-fibrotic role in lymphedema and either directly or indirectly regulate CD4+ cell accumulation and Th2 differentiation. Finally our findings suggest that lymphedema associated macrophages are a major source of VEGF-C and that impaired macrophage responses after lymphatic injury results in decreased lymphatic function.

BACKGROUND: Although bone repair is often a relatively rapid and efficient process, many bone defects do not heal. Because an adequate blood supply is essential for new bone formation, we hypothesized that augmenting new blood vessel formation by increasing the number of circulating vasculogenic progenitor cells (PCs) with AMD3100 and enhancing their trafficking to the site of injury with recombinant human parathyroid hormone (rhPTH) will improve healing. METHODS: Critical-sized 3-mm cranial defects were trephined into the right parietal bone of C57BLKS/J 6 mice (N = 120). The mice were divided into 4 equal groups (n = 30 for each). The first group received daily subcutaneous injections of AMD3100 (5 mg/kg). The second group received daily subcutaneous injections of rhPTH (5 mg/kg). The third group received both AMD3100 and rhPTH. The fourth group received subcutaneous injections of saline. Circulating vasculogenic PC numbers, new blood vessel formation, and bony regeneration were assessed. Progenitor cell adhesion, migration, and tubule formation were assessed in the presence of rhPTH and AMD3100. RESULTS: Flow cytometry demonstrated that combination therapy significantly increased the number of circulating PCs compared with all other groups. In vitro, AMD3100-treated PCs had significantly increased adhesion migration, and tubule formation was assessed in the presence of rhPTH. Combination therapy significantly improved new blood vessel formation in those with cranial defect compared with all other groups. Finally, bony regeneration was significantly increased in the combination therapy group compared with all other groups. CONCLUSIONS: The combination of a PC-mobilizing and traffic-enhancing agent improved bony regeneration of calvarial defects in mice.

Background Selection of a vascular pedicle for autologous breast reconstruction is time consuming and depends on visual evaluation during the surgery. Preoperative imaging of donor site for mapping the perforator artery anatomy greatly improves the efficiency of perforator selection and significantly reduces the operative time. In this article, we present our experience with magnetic resonance angiography (MRA) for perforator vessel mapping including MRA technique and interpretation. Methods We have performed over 400 MRA examinations from August 2008 to August 2013 at our institution for preoperative imaging of donor site for mapping the perforator vessel anatomy. Using our optimized imaging protocol with blood pool magnetic resonance imaging contrast agents, multiple donor sites can be imaged in a single MRA examination. Following imaging using the postprocessing and reporting tool, we estimated incidence of commonly used perforators for autologous breast reconstruction. Results In our practice, anterior abdominal wall tissue is the most commonly used donor site for perforator flap breast reconstruction and deep inferior epigastric artery perforators are the most commonly used vascular pedicle. A thigh flap, based on the profunda femoral artery perforator has become the second most used flap at our institution. In addition, MRA imaging also showed evidence of metastatic disease in 4% of our patient subset. Conclusion Our MRA technique allows the surgeons to confidently assess multiple donor sites for the best perforator and flap design. In conclusion, a well-performed MRA with specific postprocessing provides an accurate method for mapping perforator vessel, at the same time avoiding ionizing radiation.

BACKGROUND: Fat grafting is limited by unpredictable long-term graft retention. The authors postulate that injury to the donor-derived microvasculature during harvest and subsequent ischemia may account for this clinical variability. They examined the use of the U.S. Food and Drug Administration-approved phosphodiesterase-5 inhibitor sildenafil citrate to protect graft microvasculature and its role in revascularization and survival. METHODS: Inguinal fat of donor Tie2/LacZ mice was infiltrated with sildenafil or saline, harvested, and transplanted onto the dorsa of recipient FVB mice. Additional donor mice were perfused with intraarterial trypsin to inactivate the fat graft microvasculature before harvest and transplantation. Differences in graft revascularization, perfusion, volume of retention, and biochemical changes were assessed. RESULTS: Surviving fat grafts were characterized by exclusively donor-derived vasculature inosculating with the recipient circulation at the graft periphery. Inactivation of donor-derived microvasculature decreased early graft perfusion and led to nearly total graft loss by 8 weeks. Sildenafil attenuated vascular ischemic injury, consistent with reductions in VCAM-1 and SDF1alpha expression at 48 hours and 4-fold increases in microvasculature survival by 2 weeks over controls. Compared with controls, targeted sildenafil treatment improved early graft perfusion, doubled graft retention at 12 weeks (83 percent versus 39 percent; p < 0.05), ultimately retaining 64 percent of the original graft volume by 24 weeks (compared to 4 percent; p < 0.05) with superior histologic features. CONCLUSIONS: Fat graft vascularization is critically dependent on maintenance of the donor microvasculature. Sildenafil protects the donor microvasculature during transfer and revascularization, increasing long-term volume retention. These data demonstrate a rapidly translatable method of increasing predictability and durability of fat grafting in clinical practice.

PURPOSE: This study evaluated the effect of the platform-switching phenomenon, the use of a smaller diameter abutment on a larger diameter implant platform. Clinical and histological outcomes of the periimplant mucosa around titanium abutments in a nonsubmerged implant were evaluated. MATERIALS AND METHODS: Ten healthy adult patients, ranging from 27 to 65 years, participated in the study. A minimum of 2 endosseous implants with immediate abutment connection was placed per patient, 1 conventional and 1 platform-switched abutment. All sites for implant placement had an adequate zone of keratinized mucosa before surgical intervention. RESULTS: No clinical signs of inflammation were observed in the periimplant soft tissue mucosa, and healing was uneventful throughout the study period. Histological findings showed abnormally thick stratified squamous epithelium for both groups with few inflammatory cells in the connective tissue and none on the surface of the epithelium. CONCLUSION: Histological findings for both conventional and platform-switched implant-abutment configurations showed a similar composition of the soft tissue. These findings were in direct agreement with previous studies.