Zwitterionic Hydrogel Activates Autophagy to Promote Extracellular Matrix Remodeling for Improved Pressure Ulcer Healing.

Yuan Li,Huacheng He,Junwen Zhang,Jiang Wu,Zhe Yao,Liping Jiang,Shishuang Jiang,Kangning Wang,Liwan Song,Cai Lin

doi:10.3389/fbioe.2021.740863

Abstract

Pressure ulcer (PU) is a worldwide problem that is hard to heal because of its prolonged inflammatory response and impaired ECM deposition caused by local hypoxia and repeated ischemia/reperfusion. Our previous study discovered that the non-fouling zwitterionic sulfated poly (sulfobetaine methacrylate) (SBMA) hydrogel can improve PU healing with rapid ECM rebuilding. However, the mechanism of the SBMA hydrogel in promoting ECM rebuilding is unclear. Therefore, in this work, the impact of the SBMA hydrogel on ECM reconstruction is comprehensively studied, and the underlying mechanism is intensively investigated in a rat PU model. The in vivo data demonstrate that compared to the PEG hydrogel, the SBMA hydrogel enhances the ECM remolding by the upregulation of fibronectin and laminin expression as well as the inhibition of MMP-2. Further investigation reveals that the decreased MMP-2 expression of zwitterionic SBMA hydrogel treatment is due to the activation of autophagy through the inhibited PI3K/Akt/mTOR signaling pathway and reduced inflammation. The association of autophagy with ECM remodeling may provide a way in guiding the design of biomaterial-based wound dressing for chronic wound repair.

Highlights

Pressure ulcer (PU), known as pressure injury (PI), refers to localized injury of the skin and the potential subcutaneous soft tissue created by severe and/or continuous pressure or pressure combined with a shear force (Whitney et al, 2006; Edsberg et al, 2016)
The lower contact angle of the SBMA hydrogel demonstrated that its hydrophilicity is higher than that of PEG
Followed by outstanding healing efficiency of zwitterionic SBMA hydrogel on acute and chronic wounds, this study first comprehensively demonstrated that the SBMA hydrogel could significantly promote wound skin extracellular matrix (ECM) remolding by the upregulation of fibronectin and laminin expression as well as inhibition of Matrix metallopeptidase2 (MMP-2)

Summary

Introduction

Pressure ulcer (PU), known as pressure injury (PI), refers to localized injury of the skin and the potential subcutaneous soft tissue created by severe and/or continuous pressure or pressure combined with a shear force (Whitney et al, 2006; Edsberg et al, 2016). Chronic wounds like PU usually involve a delayed healing process due to the complex situation of wound microenvironment such as excessive inflammation reaction and impaired ECM deposition as well as inhibited vascularization caused by local hypoxia and repeated ischemia/reperfusion. Local administration alone is often difficult to exert the effect of the drugs fully and permanently. Advances in biomaterials such as nanoparticles (Hasan et al, 2019; Nguyen et al, 2019; Wu et al, 2021), hydrogels (Wu et al, 2018), films (Chen Y et al, 2020), scaffolds (De Angelis et al, 2019; Wang S et al, 2019), and gauzes (Li et al, 2020; Xiao et al, 2020) make it possible to synthesize effective delivery systems for PU treatment

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Conclusion