Abstract

Recent studies have shown that the hydrogels formed by composite biomaterials are better choice than hydrogels formed by single biomaterial for tissue repair. We explored the feasibility of the composite hydrogel formed by silk fibroin (SF) and silk sericin (SS) in tissue repair for the excellent mechanical properties of SF, and cell adhesion and biocompatible properties of SS. In our study, the SF SS hydrogel was formed by SF and SS protein with separate extraction method (LiBr dissolution for SF and hot alkaline water dissolution for SS), while SF-SS hydrogel was formed by SF and SS protein using simultaneous extraction method (LiBr dissolution for SF and SS protein). The effects of the two composite hydrogels on the release of inflammatory cytokines from macrophages and the wound were analyzed. Moreover, two hydrogels were used to encapsulate and deliver human umbilical cord mesenchymal stem cell derived exosomes (UMSC-Exo). Both SF SS and SF-SS hydrogels promoted wound healing, angiogenesis, and reduced inflammation and TNF-α secretion by macrophages. These beneficial effects were more significant in the experimental group treated by UMSC-Exo encapsulated in SF-SS hydrogel. Our study found that SF-SS hydrogel could be used as an excellent alternative to deliver exosomes for tissue repair.

Highlights

  • As the biggest organ, skin functions as a barrier to protect the body from pathogen invasion and to prevent fluid loss

  • After 48 h of culture, exosomes were isolated from umbilical cord mesenchymal stem cells (UMSCs) culture supernatants which was centrifuged at 2,000 g for 30 min to remove dead cells and debris, and centrifuged at 10,000 g for 40 min to remove large extracellular vesicles, the medium was transferred to a new tube containing 0.5 volumes of Total Exosome Isolation reagent (Life Technology, Grand Island, NY, USA)

  • Western blot showed that Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was highly expressed in the UMSC, whereas exosomes-specific markers CD9 and CD63 were only detected in UMSC-Exo (Figure 1A)

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Summary

Introduction

Skin functions as a barrier to protect the body from pathogen invasion and to prevent fluid loss. Skin often suffers from injuries caused by burns, diabetes, and ulceration, which cause infections, as well as physical and mental pain of the individual [1]. Many ongoing research efforts have been focused on developing methods to promote wound healing. Those method should keep the wound from being infected and allow gas exchange, adsorb excrescent wound exudates and maintain the local moisture of the wound to accelerate the healing [2]. Stem cell and exosomes have emerged as promising strategies for skin repair. Exosomes are 30–100 nm extracellular vesicles that can be secreted by almost all cells, and stem cell-derived exosomes have been shown to accelerate the healing of skin wound [3].

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