Wharton’s jelly MSC-derived extracellular vehicles-loaded hyaluronic acid-alginate adhesives for treatment of osteoarthritis

摘要

The repair of cartilage injury caused by osteoarthritis(OA)has long plagued clinicians.Mesenchymal stem cell(MSC)-derived small extracellular vesicles(sEVs)show great potential in cartilage regeneration and immunoregulation to realise cell-free therapy.However,unprotected sEVs are prone to be washed away by the flow of fluids and degraded in vivo.In this work,we successfully revealed that human Wharton’s jelly of umbilical cord-derived MSC(hWJMSC)sEVs promote proliferation,inhibit apoptosis,and attenuate the inflammation of chondrocytes in vitro.In light of the long period required for cartilage regeneration,we synthesised an injectable and adhesive aldehyded sodium alginate crosslinked acylhydrazide-modified hyaluronic acid(ALG-CHO/HHA)hydrogel loaded with sEVs to boost the reparative effect of the sEVs.The hydrogel-bearing sEVs was injected into cartilage defects where they adhered to the cartilage surface.In this configuration,the sEVs were delivered in a sustainable manner with the degradation of the hydrogel at the injury sites,thus contributing to highly efficient cartilage repair by regulating the regenerative and immune microenvironment.The ALG-CHO/HHA-sEV platform meets the clinical demand for long-lasting repair with a single injection.Thus,this work provides a new idea and theoretical basis for the clinical application of sEVs in the treatment of OA.