Impaired wound healing in diabetic patients is associated with deficiencies in the production of factors involved in cell proliferation and migration, such as vascular endothelial growth factor. However, it remains unclear how the transcriptional regulation of the genes encoding these factors is affected by the diabetic environment. Hypoxia-inducible factor-1alpha (Hif-1alpha), the regulatory subunit of the Hif-1 transcription factor, plays an important role in activating many of these genes. Therefore, we tested whether Hif-1alpha function is impaired in the diabetic wound environment and whether restoring Hif-1 function improves wound healing. Here, we show that Hif-1alpha protein levels are dramatically reduced in wounds of leptin receptor-deficient diabetic mice compared with nondiabetic littermates. Reduction in Hif-1alpha levels results in decreased DNA-binding activity and in decreased expression of several Hif-1 target genes, including vascular endothelial growth factor, heme oxygenase-1, and inducible nitric oxide synthase. Furthermore, we demonstrate that sustained expression of Hif-1alpha in leptin receptor-deficient diabetic wounds restores expression of these factors, enhances angiogenesis, and significantly accelerates wound healing. Taken together, these results suggest that Hif-1alpha function plays a significant role in wound healing and reduced levels of Hif-1alpha may contribute to impaired healing.

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Peripheral nerve injuries are a serious health concern and leave many patients with lifelong disabilities. There is little information about incidences, current practice, outcomes, and type of research that may help delineate new strategies. A questionnaire was designed to determine characteristics of peripheral nerve injuries and the need for alternative strategies and sent to 889 plastic, hand, trauma, and orthopedic surgeons in 49 countries; 324 completed surveys were collected and analyzed (total response rate of 36.45%). The majority of institutions treat more than 3000 patients annually. Trauma was the leading cause of injury with the majority located on the upper extremity. In most cases, a primary repair was achieved, but 2.52% were unrepairable. The overall outcome was linked to their Sunderland classification (SCL). A grade 1 nerve injury (SCL-1) reached a maximum outcome after 7.15 months. SCL-2, -3, -4, and -5 needed 10.69, 14.08, 17.66, and 19.03 months, respectively. Tissue engineering was considered the most important research field, resulting in a visual analogue scale of 8.6. Despite marked advances in the treatment of peripheral nerve injuries, clinical outcomes still appear unsatisfactory. The importance of research in the field of tissue engineering should be emphasized as a pathway toward improving these outcomes.

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Since its introduction 20 years ago for the treatment of chronic wounds, negative pressure wound therapy use has expanded to a variety of other wound types. Various mechanisms of action for its efficacy in wound healing have been postulated, but no unifying theory exists. Proposed mechanisms include induction of perfusion changes, microdeformation, macrodeformation, exudate control and decreasing the bacterial load in the wound. We surmise that these different mechanisms have varying levels of dominance in each wound type. Specifically, negative pressure wound therapy is beneficial to acute open wounds because it induces perfusion changes and formation of granulation tissue. Post-surgical incisional wounds are positively affected by perfusion changes and exudate control. In the context of chronic wounds, negative pressure wound therapy removes harmful and corrosive substances within the wounds to affect healing. When skin grafts and dermal substitutes are used to close a wound, negative pressure wound therapy is effective in promoting granulation tissue formation, controlling exudate and decreasing the bacterial load in the wound. In this review, we elucidate some of the mechanisms behind the positive wound healing effects of negative pressure wound therapy, providing possible explanations for these effects in different wound types.