These data provide profound insights into the mechanism of action of the vacuum-assisted closure device, providing an explanation for the increases in wound bed vascularity and cell proliferation based on its components. Results suggest that the vascular response is related to the polyurethane foam, whereas tissue strains induced by the vacuum-assisted closure device stimulated cell proliferation.

The incidence and prevalence of chronic and diabetic wounds are increasing and clinical treatments to tackle these epidemics are still insufficient. In this study, we tested the ability of freeze-dried platelet-rich plasma (PRP) and an allogenic micronized acellular dermal matrix alone and in combination to modulate diabetic wound healing. Therapeutic materials were applied to 1.0 cm 2 excisional wounds on genetically diabetic (db/db) mice. Wound-healing kinetics and new tissue formation were studied at 9 and 21 days posttreatment. Quantitative immunohistochemistry was used to study vascularity and cellular proliferation (days 9 and 21), and collagen deposition was evaluated 21 days postwounding. In vitro, micronized allogenic dermis, when combined with PRP, absorbed nearly 50% of original platelet-derived growth factor, transforming growth factor-b, vascular endothelial growth factor, and epidermal growth factor from platelets and stimulated fibroblast proliferation. In vivo, micronized dermis increased the formation of vascularized wound tissue by day 9. Freeze-dried PRP alone or in combination with micronized dermis increased wound tissue revascularization and proliferation compared with spontaneous healing. The increase in cell proliferation persisted until day 21 only when freeze-dried PRP was used in combination with micronized dermis. These results indicate that micronized allogenic dermis may be used to provide a dermal matrix to stimulate tissue formation and the combination with PRP may confer additional beneficial growth factors to chronic or diabetic wounds.Several strategies to stimulate diabetic wound healing have evolved over the last decade including biological approaches, such as topical recombinant platelet-derived growth factor (PDGF), 1 autologous PDGFs, 2 and devices such as the VAC.3 Despite these considerable advances in wound care, diabetic wounds have remained difficult to heal, are painful, prone to recurrence, and may lead to amputation. 4,5 Autologous platelet-rich plasma (PRP), delivering multiple growth factors, 6 has been used on a large number of patients. The results from these studies, mainly collected retrospectively, suggest that the efficacy may be limited to specific subpopulations of wounds. 7 The mixed results might relate to variability in the growth factor profiles among different patient populations and ways of delivering or activating platelets.2 Our laboratory has shown previously that reconstituted, freeze-dried PRP stimulates early angiogenesis and cell proliferation in a genetic diabetic mouse model, 8 offering a viable method for extending the shelf-life of allogenic PRP for wound healing. However, the current method of applying PRP to wounds used in most studies-including our own-is limited by thrombin activation, which simultaneously triggers the release of all platelet growth factors, including pro-and antiangiogenic factors, 6 initially having antagonistic effects.

Diabetic patients suffer from impaired wound healing, characterized by only modest angiogenesis and cell proliferation. Stem cells may stimulate healing, but little is known about the kinetics of mobilization and function of bone marrow progenitor cells (BM-PCs) during diabetic wound repair. The objective of this study was to investigate the kinetics of BM-PC mobilization and their role during early diabetic wound repair in diabetic db/db mice. After wounding, circulating hematopoietic stem cells (Lin(-)c-Kit(+)Sca-1(+)) stably increased in the periphery and lymphoid tissue of db/db mice compared to unwounded controls. Peripheral endothelial progenitor cells (CD34(+)VEGFR(+)) were 2.5- and 3.5-fold increased on days 6 and 10 after wounding, respectively. Targeting the CXCR4-CXCL12 axis induced an increased release and engraftment of endogenous BM-PCs that was paralleled by an increased expression of CXCL12/SDF-1α in the wounds. Increased levels of peripheral and engrafted BM-PCs corresponded to stimulated angiogenesis and cell proliferation, while the addition of an agonist (GM-CSF) or an antagonist (ACK2) did not further modulate wound healing. Macroscopic histological correlations showed that increased levels of stem cells corresponded to higher levels of wound reepithelialization. After wounding, a natural release of endogenous BM-PCs was shown in diabetic mice, but only low levels of these cells homed in the healing tissue. Higher levels of CXCL12/SDF-1α and circulating stem cells were required to enhance their engraftment and biological effects. Despite controversial data about the functional impairment of diabetic BM-PCs, in this model our data showed a residual capacity of these cells to trigger angiogenesis and cell proliferation.

Tension is a principal force experienced by skin and serves a critical role in growth and development. Optimal tension application regimens may be an important component for skin tissue engineering and dermatogenesis. In this study, we designed and tested a novel servo-controlled skin-stretching device to apply predetermined tension and waveforms in mice. The effects of static and cyclical stretching forces were compared in 48 mice by measuring epidermal proliferation, angiogenesis, cutaneous perfusion, and principal growth factors using immunohistochemistry, real-time reverse transcriptase-polymerase chain reaction, and hyperspectral imaging. All stretched samples had upregulated epidermal proliferation and angiogenesis. Real-time reverse transcriptase-polymerase chain reaction of epidermal growth factor, transforming growth factor beta1, and nerve growth factor demonstrated greater expression in cyclically stretched skin when compared to static stretch. Hypoxia-induced factor 1alpha was significantly upregulated in cyclically stretched skin, but poststretch analysis demonstrated well-oxygenated tissue, collectively suggesting the presence of transient hypoxia. Waveform-specific mechanical loads may accelerate tissue growth by mechanotransduction and as a result of repeated cycles of temporary hypoxia. Further analysis of mechanotransduction signaling pathways may provide additional insight to improve skin tissue engineering methods and optimize our device.

Introduction-Platelets partake in hemostasis, wound healing and tumor growth. Although platelet-rich-plasma (PRP) has been used in surgery for several years, its mechanism of action and application methods are still poorly characterized.

Residents acknowledged that additional challenges exist for female residents in becoming resuscitation team leaders. Increasing awareness in residency program leadership is key to affecting change to ensure all residents are trained in a similar manner, while also addressing gender-specific needs of residents where appropriate. We present suggestions for addressing these barriers and incorporating discussion of leadership styles into residency training.

Short vacuum-assisted closure treatment induced an extended biological response in the wound. A total of 12 hours of periodically applied vacuum-assisted closure reached a similar wound tissue response as continuously applied vacuum-assisted closure for 7 days. These findings suggest new clinical approaches for mechanical wound-healing devices.

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