Abstract

Multilayer composite membrane of biomaterials can increase the function of adipose stem cells or osteoprogenitor cells. Recent evidence indicates endothelial progenitor cells (EPCs) and EPCs released microvesicles (MVs) play important roles in angiogenesis and vascular repair. Here, we investigated the effects of biomaterial multilayer membranes of hyaluronic acid (HA) or chondroitin sulfate (CS) and Collagen I (Col I) on the functions and MVs release of EPCs. Layer-by-layer (LBL) technology was applied to construct the multilayer composite membranes. Four types of the membranes constructed by adsorbing either HA or CS and Col I alternatively with different top layers were studied. The results showed that all four types of multilayer composite membranes could promote EPCs proliferation and migration and inhibit cell senility, apoptosis, and the expression of activated caspase-3. Interestingly, these biomaterials increased the release and the miR-126 level of EPCs-MVs. Moreover, the CS-Col I membrane with CS on the top layer showed the most effects on promoting EPCs proliferation, EPCs-MV release, and miR-126 level in EPCs-MVs. In conclusion, HA/CS and Collagen I composed multilayer composite membranes can promote EPCs functions and release of miR-126 riched EPCs-MVs, which provides a novel strategy for tissue repair treatment.

Highlights

  • Medical biomaterials for the repair or replacement of tissue or organs are polymeric substances

  • We investigated the effects of different multilayer membranes (HA-Col I or chondroitin sulfate (CS)-Col I) with different top layers (HA, CS, or Col I) on endothelial progenitor cells (EPCs) cell proliferation, migration, apoptosis, senescence, and MV release and miR126 carry

  • Western blot data showed that the cleaved caspase3 level, which was associated with induction of apoptosis, was inhibited by multilayer composite membranes (versus vehicle; Figure 1(c))

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Summary

Introduction

Medical biomaterials for the repair or replacement of tissue or organs are polymeric substances. Biomaterials like hyaluronic acid (HA), chondroitin sulfate (CS), and Collagen (Col) have biological activities on stem cells [1]. Fibril-forming Col I (Col I) as one of the most abundant matrix proteins can affect the growth, spread, and differentiation of stem cells [2,3,4]. Glycosaminoglycans like HA and CS, as the extracellular matrix (ECM) components cooperating with numerous cell surface adhesive proteins (e.g., fibronectin) and cytokines (growth factors), can impinge on cell biological processes such as growth and differentiation [5, 6]. CS can promote the organization of soluble Col I precursors into fibrillar form which is essential for ECM structure and function, affecting the activity of adipose stem cells [7]. The LBL multilayer film with HA-Col I or CS-Col I as raw materials could modulate fibroblast cell and osteoprogenitor stem cell functions (proliferation, migration, and regeneration) and

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