Negative pressure wound therapy enhances bone regeneration compared with conventional therapy in a rabbit radius gap‑healing model

Abstract

Negative pressure wound therapy (NPWT) has been recognized as an effective method for the treatment of intractable wounds. However, its effects on bone healing remain to be elucidated. Our previous study demonstrated that NPWT induced cell proliferation and osteoblastic differentiation of rat periosteum-derived mesenchymal stem cells (P-MSCs). It was reported that following NPWT treatment, the expression of the mechanotransduction molecule integrin β5 is increased, indicating that NPWT may serve an active role in fracture healing by enhancing bone formation and reducing bone resorption. The present study sought to further investigate the efficacy of NPWT on the bone regeneration process in a rabbit radial gap-healing model. All rabbits with radial defects were randomly divided into two groups: NPWT and control groups. Continuous negative pressure at-125 mmHg was applied to all rabbits. Furthermore, X-ray imaging and scoring on day 7, 14, 21 and 28 postoperatively were performed to evaluate new bone formation. Histological changes were determined via hematoxylin and eosin and Masson's trichrome staining at 2-and 4-weeks following surgery. In addition, vimentin-positive cells located in the periosteum were detected via immunohistochemical examination on day 3 post operation. Finally, protein expression levels of vascular endothelial growth factor (VEGF), bone morphogenetic protein (BMP)-2 and osteopontin (OPN) were evaluated using western blot analysis on the 2nd and 4th week following NPWT. X-ray and histological examination revealed that the bone-healing processes in the NPWT group were faster compared with the control group. Additionally, compared with the control group, the NPWT group exhibited higher X-ray scores, increased percentage of positive vimentin-stained cells and upregulated expression of VEGF, BMP-2 and OPN proteins. The aforementioned findings suggest that NPWT, under a continuous negative pressure of-125 mmHg, may accelerate bone regeneration by enhancing MSC proliferation, osteoblastic differentiation and VEGF, BMP-2 and OPN expression.

Combined computational analysis and cytology show limited depth osteogenic effect on bone defects in negative pressure wound therapy

“…Further, we conducted the verification of proliferation and osteogenic differentiation of BMSCs, and the results confirm that −120 mmHg NP demonstrated the optimal osteogenic effect compare with other NP scales ( Figure 14 ). This osteogenic differentiation was also verified by clinical practice and experimental findings ( Kim and Lee, 2019 ; Zhu et al, 2021 ). One would argue that osteogenesis is a combined effect of fluid shear stress and NP within the marrow cavity; however, studies have shown that hydrodynamic shear stress induces prostaglandin synthesis, activation of kinases ERK and JNK, and mRNA expression of Runx2, ALP, COL1A1, VEGF, BMP-2, BMP -7 and TGF-β1, but does not stimulate cell proliferation in osteoblasts and MSCs ( Kreke et al, 2008 ; Sharp et al, 2009 ; Yu et al, 2014 ).…”

“…NPWT promotes angiogenesis and granulation in part by the strain-induced production of growth factors and cytokines, and most of these findings were recognized under an NP of −120 or −125 mmHg ( Glass et al, 2014 ), which is most effective for soft-tissue wounds ( Argenta and Morykwas, 1997 ; Morykwas et al, 1997 ; Morykwas et al, 2001 ; Chen et al, 2017 ; Liu et al, 2018b ; Wu et al, 2022 ). In a bone tissue, which is a hard tissue, BMSCs osteogenesis activation and osteoclasts inhibition were also found under a short time continuous NP of −125 mmHg via kinds of osteogenic factors, such as vascular endothelial growth factor, bone morphogenetic protein-2, osteopontin, mechanotransduction molecule integrin β5, alkaline phosphatase, collagen1α2 and hypoxia-inducible factor-1α( Zhu et al, 2014 ; Wang et al, 2020 ; Zhu et al, 2021 ). The mechanisms by which NP activates mechanotransductive signaling pathways and stimulates the osteoblastic phenotype have not been elucidated.…”

“…Extrinsic mechanical cues and suitable stiffness can promote osteoblast differentiation in vitro and endochondral ossification of MSCs ( Pelaez et al, 2012 ; Steward and Kelly, 2015 ). A few in vitro and in vivo studies have suggested that under suitable continuous or intermittent NPWT, bone regeneration may be accelerated by enhancing MSC proliferation, osteoblastic differentiation, and osteogenesis-related cytokine expression ( Zhang et al, 2013 ; Yang et al, 2014 ; Zhu et al, 2021 ). Another study identified a novel autophagy axis by which negative pressure promotes osteoblast differentiation of MSCs and bone regeneration ( Zhang et al, 2022 ).…”

The role of integrin family in bone metabolism and tumor bone metastasis

“…Depolarization and hyperpolarization after mechanical stimulation were inhibited by integrin α v , α 5 , β 1 , and β 5 blockers [104]. Negative pressure wound therapy (NPWT) has been recognized as an effective method for healing bone injury [105][106][107]. Cell experiments demonstrated that NPWT promoted the proliferation and osteogenic differentiation of periosteum-derived MSCs.…”

Roles of negative pressure wound therapy for scar revision

“…Vascular endothelial growth factor and angiopoietin-2 (Ang-2) levels in the wound are much higher in NPWT, which may be caused by the closed and hypoxic environment ( Ma et al, 2016 ; Yang et al, 2021 ; Zhu et al, 2021 ). Negative pressure provides effective and continuous power to the local circulation of the wound, reducing the seroma and hematoma, as compared with traditional dressing ( Nagata et al, 2018 ; Mangelsdorff et al, 2019 ; Zwanenburg et al, 2020 ; Bueno-Lledo et al, 2021 ).…”