Effects of Negative Pressure Wound Therapy on Mesenchymal Stem Cells Proliferation and Osteogenic Differentiation in a Fibrin Matrix

Abstract

Vacuum-assisted closure (VAC) negative pressure wound therapy (NPWT) has been proven to be an effective therapeutic method for the treatment of recalcitrant wounds. However, its role in bone healing remains to be unclear. Here, we investigated the effects of NPWT on rat periosteum-derived mesenchymal stem cells (P-MSCs) proliferation and osteoblastic differentiation in a 3D fibrin matrix. P-MSCs underwent primary culture for three passages before being used to construct cell clots. The fibrin clots were incubated with NPWT under continuous suction at −125 mmHg in a subatmospheric perfusion bioreactor. Clots exposed to atmospheric pressure served as the static control. Compared to the control group, cell proliferation significantly increased in NPWT group after incubation for 3 days. There was no statistical difference in apoptosis rate between two groups. The ALP activity and mineralization of P-MSCs all increased under continuous suction. The expressions of collagen type 1 and transcription factor Cbfa-1 were higher at the 1-, 3-, and 7-day timepoints and the expressions of osteocalcin and integrin β5 were higher at the 3-, and 7-day timepoints in the NPWT group. These results indicate that a short time treatment with NPWT, applied with continuous suction at −125 mmHg, can enhance cellular proliferation of P-MSCs and induce the differentiation toward an osteogenic phenotype. The mechanotransduction molecule integrin β5 was found to be highly expressed after NPWT treatment, which indicates that NPWT may play a positive role in fracture healing through enhance bone formation and decrease bone resorption.

Interaction of material stiffness and negative pressure to enhance differentiation of bone marrow‐derived stem cells and osteoblast proliferation

“…In addition, negative pressure induced expression of HIF1α that is responsible for upregulation of a broad range of angiogenic factors, including VEGF, SDF1, and PDGF (Rey & Semenza, ). These findings are consistent with Yang et al, who reported increased ALP activity and synthesis of type I collagen and VEGF by human MSCs with 30‐min treatments of negative pressure applied twice daily (Yang et al, ), and those of Zhu et al who reported increased ALP activity and expression of COL1A1, osteocalcin, and ALP by rat MSCs after 3 and 7 days of continuous negative pressure (Zhu et al, ).…”

“…These results are consistent with findings of Zhu et al with rat periosteum‐derived MSCs in a 3D fibrin matrix. Specifically, they observed that cells were more spread in their fibrin gels and exhibited increased cell density and ALP activity with 72 hr of continuous negative pressure (−125 mmHg; Zhu, Yu, Qi, Li, & Hu, ). Switching to human and rat MSCs, it was found that MSCs cultured on BRM exhibited increased expression of osteoblastic genes ALP, OPN , and COL1A2 under negative pressure.…”

Effect of Topical Administration of Fractions and Isolated Molecules from Plant Extracts on Skin Wound Healing: A Systematic Review of Murine Experimental Models

“…An evident example was the wide variation in wound area and time of wound closure. These considerations are important because they are directly associated with the tensile force experienced by the tissue, which profoundly affect the speed and quality of skin repair [59, 60]. Our findings show that 20% of the studies that utilized fractions neglected the analysis of wound closure, an essential piece of information to assess the ability of any intervention to stimulate the healing process.…”

“…During the formation of granulation tissue, there is predominance of sulfated molecules which attract water, facilitating the cellular migration, and also serve as a support structure for the first formed collagen (type III collagen) [65]. There are enough evidences that the synthesis and differentiation of cells and matrix components are crucial for a normal wound closure [60]. It is already known that the oxidative stress induces cell damage, lipid, protein, and nucleic acids oxidation [66, 67].…”

Results of negative pressure wound therapy in compound grade 3 tibial fractures

“…Also, with its ability to promote healing of fractures as shown by Zhu et al by stimulating mesenchymal stem cell proliferation and osteogenic differentiation NPWT may play and stimulate healing of fractures itself. 6 This study is a prospective randomised control study of 30 patients which aims to study the utility of NPWT in compound tibial fractures with respect to its impact on wound healing and soft tissue cover in a setting of a tertiary care centre. The observations of this study were subjected to comparison with the observations made by different authors.…”