Negative pressure wound therapy(NPWT) has significantly advanced wound care over the past two decades. Although NPWT continues to find new therapeutic applications, the physiological effect of NPWT on the surrounding tissues remains a subject of debate. The postulated primary mechanisms include macrodeformation, microdeformation, fluid removal, and alteration of the wound environment and secondary mechanisms include neurogenesis, angiogenesis, modulation of inflammation, and alterations in bioburden. These processes are postulated to be governed by differential gene expression at the wound bed under NPWT. We aimed to systematically review the currently available evidence on the effects of NPWT on the differential gene and cellular biomarker expression profiles in open surgical wounds.

This review was registered in the PROSPERO database(CRD42022303088) and conducted according to the PRISMA Guidelines. Medline, Embase and EBSCO databases, and Clinical trial registries were searched from inception to December 2021. Risk of Bias assessment was performed using the RoBANS tool for non-randomized studies, the COCHRANE's Risk of Bias 2(ROB-2) tool for randomized clinical studies, OHAT tool for in-vitro studies or the SYRCLE tool for animal model studies. A descriptive summary was collated and the aggregated data is presented as a narrative synthesis. Discrepancies were resolved by discussion amongst the authors and a tie-breaking vote from the authors not involved in the screening process. Clinical studies, animal models or in-vitro studies that quantitatively or semi-quantitatively evaluated the influence of NPWT on growth factors, cytokine or gene expression in the circulation or wound bed were included.

Out of 5567 potential studies, 38 studies involving 1096 subjects were included in the systematic review. This included 21 clinical studies, 14 animal models and 3 in-vitro studies. Out of the 14 animal models, 3 studies were conducted in rabbit models,5 studies were conducted in murine models and 6 studies in porcine models. 18 studies had a high risk of bias and 4 studies had an unclear risk of bias. 15 clinical studies and 12 animal studies analysed tissue samples from wounds while 5 clinical studies analysed the wound effluent. 5 clinical studies and 2 animal studies also used serum samples to correlate the effect of NPWT on wounds. 35 studies focussed on the effect of NPWT on molecular and cellular biomarkers, while 3 focussed on the effect of NPWT on differential gene expression in wound or serum samples. VEGF(Vascular Endothelial Growth Factor) was elevated in all 9 studies which studied its effects. Tumour necrosis Factor alpha(TNF α) was downregulated in 6 out of 7 studies, Transforming Growth Factor Beta(TGF β) was upregulated in 4 out of 4 studies, Fibronectin was upregulated in both studies which evaluated its effects. Equivocal results were obtained across all studies with respect to Interleukins(IL) and Matrix Metalloproteinases(MMP) including IL1β,IL 6,IL8,IL8, MMP 2,3 and 9. The effects of NPWT on 43 other molecular biomarkers and 13 different gene expressions were analysed across all studies.

NPWT stimulates modulation of numerous local and circulating cytokines and growth factor expressions to promote an anti-inflammatory profile. This is most likely achieved by downregulation of TNFα, upregulation of VEGF, TGF-β and fibronectin. This review has also identified many other biomarkers and gene expressions of interest to direct future research.