miR‐23a‐3p‐abundant small extracellular vesicles released from Gelma/nanoclay hydrogel for cartilage regeneration

Abstract

Articular cartilage has limited self-regenerative capacity and the therapeutic methods for cartilage defects are still dissatisfactory in clinic. Recent studies showed that exosomes derived from mesenchymal stem cells promoted chondrogenesis by delivering bioactive substances to the recipient cells, indicating exosomes might be a novel method for repairing cartilage defect. Herein, we investigated the role and mechanism of human umbilical cord mesenchymal stem cells derived small extracellular vesicles (hUC-MSCs-sEVs) on cartilage regeneration. In vitro results showed that hUC-MSCs-sEVs promoted the migration, proliferation and differentiation of chondrocytes and human bone marrow mesenchymal stem cells (hBMSCs). MiRNA microarray showed that miR-23a-3p was the most highly expressed among the various miRNAs contained in hUC-MSCs-sEVs. Our data revealed that hUC-MSCs-sEVs promoted cartilage regeneration by transferring miR-23a-3p to suppress the level of PTEN and elevate expression of AKT. Moreover, we fabricated Gelatin methacrylate (Gelma)/nanoclay hydrogel (Gel-nano) for sustained release of sEVs, which was biocompatible and exhibited excellent mechanical property. In vivo results showed that hUC-MSCs-sEVs containing Gelma/nanoclay hydrogel (Gel-nano-sEVs) effectively promoted cartilage regeneration. These results indicated that Gel-nano-sEVs have a promising capacity to stimulate chondrogenesis and heal cartilage defects, and also provided valuable data for understanding the role and mechanism of hUC-MSCs-sEVs in cartilage regeneration.

Enhancement of acellular cartilage matrix scaffold by Wharton's jelly mesenchymal stem cell-derived exosomes to promote osteochondral regeneration

“…Liu X confirmed that the imine cross-linked hydrogel containing MSC-Exos has the ability to promote cartilage regeneration [ 55 ], but the mechanism and role of MSC-Exos in the process of cartilage regeneration are still unclear. Our study confirms that hWJMSC-Exos can promote the migration and proliferation of BMSCs in vitro and can promote the proliferation of chondrocytes, which is consistent with the results of Hu H's research [ 62 ]. Studies by Zhang S [ 63 ] and Woo CH [ 47 ] confirmed that Exos derived from human embryonic stem cell-derived MSCs and human adipose-derived MSCs have similar biological functions.…”

Adipose-derived Mesenchymal Stem Cell-derived Exosomes Promote Tendon Healing by Activating Both SMAD1/5/9 and SMAD2/3

“…For instance, Aubin et al attempted to change the proliferative arrangement of different cells using micropatterned GelMA to provide a theoretical basis for constructing functional tissues in vitro [43]. Zou et al used GelMA to construct biomimetic bone with a trabecular bone structure and Hu et al used GelMA microspheres loaded with small extracellular vesicles to promote cartilage regeneration [44,45]. In the current study, GelMA was used as a carrier of ADSC-Exos to provide a good microenvironment for exosome storage and their gradual absorption.…”

Extracellular Vesicles in Musculoskeletal Pathologies and Regeneration

“…As EVs maybe cleared rapidly from joint space, they have been used as therapeutic substances encapsulated and embedded in drug-delivery systems consisting of different matrices, which help to achieve sustained effects. These biomaterials are photo-induced imine crosslinking hydrogel glue, gelatin methacrylate/nanoclay hydrogel or solid 3D printed cartilage ECM/gelatine methacrylate (GelMA) scaffolds (Liu et al, 2017b ; Chen et al, 2019 ; Hu et al, 2020 ). Liu et al implanted an acellular tissue patch (EHG) consisting of a hydrogel glue blended with human iPSC-MSC-EVs into a rabbit articular cartilage defect.…”