Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration

Abstract

The regeneration of articular cartilage, which scarcely shows innate self-healing ability, is a great challenge in clinical treatment. Stem cell-derived exosomes (SC-Exos), an important type of extracellular nanovesicle, exhibit great potential for cartilage regeneration to replace stem cell-based therapy. Cartilage regeneration often takes a relatively long time and there is currently no effective administration method to durably retain exosomes at cartilage defect sites to effectively exert their reparative effect. Therefore, in this study, we exploited a photoinduced imine crosslinking hydrogel glue, which presents excellent operation ability, biocompatibility and most importantly, cartilage-integration, as an exosome scaffold to prepare an acellular tissue patch (EHG) for cartilage regeneration. It was found that EHG can retain SC-Exos and positively regulate both chondrocytes and hBMSCs in vitro. Furthermore, EHG can integrate with native cartilage matrix and promote cell deposition at cartilage defect sites, finally resulting in the promotion of cartilage defect repair. The EHG tissue patch therefore provides a novel, cell-free scaffold material for wound repair.

Exosomes in osteoarthritis and cartilage injury: advanced development and potential therapeutic strategies

“…They suggested that the ability of diffusing through the hydrogel of smaller exosomes contributed to the results. Liu et al exploited a photoinduced imine crosslinking hydrogel glue as an exosome scaffold to prepare an acellular tissue patch for cartilage regeneration [71] . They found that most of the encapsulated exosomes were retained inside the hydrogel (>90%) after immersing in PBS for 14 days.…”

Extracellular vesicle and mesenchymal stem cells in bone regeneration: recent progress and perspectives

“…Meanwhile, Zhang et al reported that exosomes combining tricalcium phosphate‐modified scaffolds boosted osteogenesis in rat calvarial bone defects, and promoted MSCs' osteoghenic differentiation in vitro. Liu et al further utilized MSCs‐derived exosomes‐modified hydrogel glue scaffolds to promote cartilage healing seamlessly of cartilage defects in a rabbit model In conclusion, EVs are promising for clinical application with biomaterials. However, more experimentation will be needed.…”

Exosomes: biology, therapeutic potential, and emerging role in musculoskeletal repair and regeneration

“…84 The EHG integrated with native cartilage matrix and promoted cell deposition at cartilage defect sites, resulting in the repair of the cartilage defect, suggesting that MSC-derived exosomes embedded in a scaffold material might be a promising strategy for the repair of connective tissues, such as cartilage. 84 Stem cell-derived exosomes have been reported to enhance bone healing. Exosomes secreted by MSCs derived from human-induced pluripotent stem cells were carried by a scaffold and implanted into calvarial defects in rats.…”