They have been rinsed and incubated for 48 h in serum-free medium. The collected conditioned medium was ultracentriand incubated for 48 h in serum-free medium. The collected conditioned medium was ultracenfuged and ultrafiltered to acquire exosomes. The RIG-I-like Receptor Proteins supplier exosomes have been mixed with AD/CS/RSF pre-gel sotrifuged and ultrafiltered to obtain exosomes. The exosomes have been mixed with AD/CS/RSF pre-gel lution, and after that H2O2 and HRP were added to induce gelation. Subsequently, the cartilage defect resolution, and then H2 O and HRP had been added exosomes released by the hydrogels was filled using the exosome-containing2adhesive hydrogel. Theto induce gelation. Subsequently, the cartilage defect was filled with and infiltrated the hydrogel and promoted BMSC proliferation and recruited BMSCs that migratedthe exosome-containing adhesive hydrogel. The exosomes released by the hydrogels differentiation into chondrocytes. By migrated and infiltrated the and neo-cartilage formation, the recruited BMSCs that inducing ECM production hydrogel and promoted BMSC proliferation and hydrogel facilitated the regeneration of cartilage defect in situ. ECM production and neo-cartilage formation, the differentiation into chondrocytes. By inducing hydrogel facilitated the regeneration of cartilage defect in situ.4. In Vivo Efficacy of Exosomes for OA Therapy Considerable Caspase-8 Proteins supplier advances in exosome-based therapies have already been demonstrated in a number of illness models [16]. Nonetheless, exosomes haven’t been utilized in OA-related studies till current years. Therapeutic effects, for example pain relief [34], cartilage defect repair [155], subchondral bone protection [35], and synovitis amelioration [30], happen to be observed in OA analysis. The delivery system of exosomes for in vivo OA therapy reported thus far has only been intra-articular injection.Bioengineering 2022, 9,16 of4. In Vivo Efficacy of Exosomes for OA Therapy Considerable advances in exosome-based therapies happen to be demonstrated in numerous disease models [16]. Having said that, exosomes have not been utilized in OA-related studies till recent years. Therapeutic effects, which include pain relief [34], cartilage defect repair [155], subchondral bone protection [35], and synovitis amelioration [30], happen to be observed in OA study. The delivery technique of exosomes for in vivo OA remedy reported thus far has only been intra-articular injection. Exosomes derived from MSCs and also other sources happen to be tested in vivo to evaluate their therapeutic effects in OA treatment. Utilized in an MIA-induced rat OA model, exosomes obtained from BM-MSCs proficiently enhanced cartilage repair, ECM synthesis, and joint pain relief [34]. IPFP-MSC-derived exosomes also prevented cartilage damage and alleviated gait abnormality inside a mouse OA model by preserving cartilage homeostasis [44]. PRP-Exos decreased the apoptotic rate of OA chondrocytes and decreased the OARSI (Osteoarthritis Study Society International) score of cartilage samples from OA joints of rabbit models [17]. SFBs overexpressing miR-126-3p generated exosomes that suppressed cartilage degeneration and inflammation in an OA rat model [50]. CPC-derived, exosome-containing EVs enhanced the repair of articular cartilage within a surgically induced mouse OA model and stimulated chondrocyte migration and proliferation in vitro by means of upregulating miRNA 221-3p [48]. Such helpful effects happen to be attributed for the function of exosomes in regulating unique signaling pathways, including mTOR, Wnt/-catenin, YAP, and no.