Negative Pressure Wound Therapy Promotes Wound Healing by Suppressing Macrophage Inflammation in Diabetic Ulcers

Abstract

Aim: This work aims to explore the biological role of negative pressure wound therapy (NPWT) in the treatment of diabetic ulcer. Materials & methods: Full-thickness skin defects were created in diabetic (db/db) and non diabetic (db/m) mice to create wound models. The mice were received NPWT or rapamycin injection. Mouse macrophage cells (Raw264.7) were treated with lipopolysaccharide to induce inflammatory response, and then received negative pressure treatment. We observed the wound healing of mice and examined gene and protein expression and CD68+ macrophage levels. Results: NPWT notably enhanced the wound closure ratio, and inhibited the LC3-II/LC3-I ratio and Beclin-1 expression in diabetes mellitus (DM) mice. NPWT decreased CD68+ macrophage levels in wound tissues of DM mice. The influence conferred by NPWT was abolished by rapamycin treatment. Negative pressure repressed the LC3-II/LC3-I ratio and the expression of Beclin-1, TNF-α, IL-6 and IL-1β in the Raw264.7 cells. Conclusion: NPWT promotes wound healing by suppressing autophagy and macrophage inflammation in DM.

Characterization of Macrophage and Cytokine Interactions with Biomaterials Used in Negative-Pressure Wound Therapy

“…Previous studies have indicated the presence of lower inflammatory cytokines with NPWT [ 16 ]. In addition, vacuum has been known to cause reduced inflammation and autophagy in macrophages [ 17 ]. Much of these studies have been performed in vivo.…”

“…This can be explained by the significantly reduced CD68+ macrophages observed during NPWT therapy [ 15 ]. A recent study explored the roles of macrophages in NPWT-mediated healing, reporting lower macrophage autophagy in NPWT-treated diabetic wounds [ 17 ]. Additionally, application of vacuum on Raw264.7 macrophages in vitro resulted in lower inflammatory activation and autophagy [ 17 ], which is expected considering the immunomodulatory influences that hypoxia has long been known to exert on macrophages within tumor niches [ 18 ].…”

“…A recent study explored the roles of macrophages in NPWT-mediated healing, reporting lower macrophage autophagy in NPWT-treated diabetic wounds [ 17 ]. Additionally, application of vacuum on Raw264.7 macrophages in vitro resulted in lower inflammatory activation and autophagy [ 17 ], which is expected considering the immunomodulatory influences that hypoxia has long been known to exert on macrophages within tumor niches [ 18 ]. These data point towards NPWT modulating chronic inflammatory activation in macrophages at wound sites to advance healing.…”

Immunology of Acute and Chronic Wound Healing

“…NPWT was reported to reduce iNOS, IL-6 and TNF-α by regulating the MAPK-JNK pathway [ 173 ]. NPWT enhanced healing of full-thickness skin defects in diabetic mice by lowering the number of CD68+ macrophages, reducing the level of pro-inflammatory cytokines TNF-α, IL-6, IL-1β and suppressing autophagy [ 174 ]. These observations emphasize the role of immunomodulatory effects in the therapeutic mechanism of accelerating chronic wound healing by negative pressure wound therapy.…”

The Immune-Centric Revolution in the Diabetic Foot: Monocytes and Lymphocytes Role in Wound Healing and Tissue Regeneration—A Narrative Review

“…It has been also observed that M1 macrophages release high concentrations of TNF-α in diabetic rats, and an in vitro high glucose environment facilitates M1 polarization, which are both detrimental to keratinocyte migration [99]. It has been recently shown that negative pressure wound therapy by suppressing autophagy and macrophage inflammation in a mouse model promotes wound healing [100]. Monocytes and macrophages are known to play important roles in neovascularization during wound healing [38,101].…”