Negative pressure wound therapy is associated with up‐regulation of bFGF and ERK1/2 in human diabetic foot wounds

Abstract

Chronic foot wounds are a leading cause of morbidity and hospitalization for patients with diabetes. Negative pressure wound therapy (NPWT) is known to promote healing of diabetic foot wounds, but the underlying molecular mechanisms remain elusive. We propose to gain molecular insights into the wound healing promoting signals underlying the effects of NPWT on diabetic foot wounds in humans. We assessed 30 patients with diabetic foot ulcers. Of these cases, 15 were treated with NPWT, while 15 patients were treated with traditional gauze therapy. Granulated tissue was harvested before and after treatment in both patient groups and histologically analyzed with hematoxylin & eosin as well as Masson's trichrome staining methods. Immunohistochemistry and Western blot analysis was performed to evaluate expression of basic fibroblast growth factor (bFGF) and extracellular signal-regulated kinase (ERK)1/2, previously associated with promoting cellular growth and/or wound healing. Unlike controls, the wounds in the NPWT-treated diabetic patients developed characteristic features of granulated tissue with increased collagen deposition. Immunohistochemical analysis also revealed an increase in bFGF levels in NPWT-treated patients. Western blot analysis further showed a significant up-regulation of bFGF and phosphorylated ERK1/2 protein levels in the NPWT-treated diabetic patients vs. controls. Our studies reveal that NPWT is associated with an up-regulation of bFGF and ERK1/2 signaling, which may be involved in promoting the NPWT-mediated wound healing response.

The effects of negative pressure treatment on the extracellular matrix gene expression and protein production of fibroblasts

“…Regarding the cellular behavior in response to negative pressure, studies have identified certain molecular basis in the wound, such as up-regulation of basic fibroblast growth factor (bFGF) and extracellular signal-regulated kinase (ERK) 1/2 [18]. However, it is difficult to observe independently in animal models or in clinical settings without being confounded by the host factors.…”

Using negative pressure wound therapy on microskin autograft wounds

“…First, both acute and chronic wounds were included in this study, and we found that NPWT in combination with microskin autografts had a good therapeutic effect. But the chronic wounds of diabetes were not included in this study, Yang et al [35] found that NPWT was associated with the upregulation of basic fibroblast growth factor and extracellular signal-regulated kinase1/2 in human diabetic foot wounds, which might be involved in promoting the NPWT-mediated diabetic wound healing. Guffanti [8] found that NPWT systems were shown to be more effective than standard moist wound therapy with regard to proportion of healed wounds and rate of wound closure for diabetic foot ulcers.…”

Negative pressure wound therapy use in diabetic foot syndrome—from mechanisms of action to clinical practice

“…Negative pressure wound therapy action results in two types of tissue deformations: macrodeformation (ie, wound contraction) and microdeformation that occurs at microscopic level. Both of them are thought to influence mostly early stages of wound healing, that is inflammatory and proliferative phases …”