Integration of human umbilical cord mesenchymal stem cells-derived exosomes with hydroxyapatite embedded hyaluronic acid-alginate hydrogel for bone regeneration

The treatment of bone defects has plagued clinicians. Exosomes, the naturally secreted nanovesicles by cells, exhibit great potential in bone defect regeneration to realize cell-free therapy. In this work, we successfully revealed that human umbilical cord mesenchymal stem cells (hUCMSCs)-derived exosomes could effectively promote the proliferation, migration and osteogenic differentiation of a murine calvariae preosteoblast cell line (MC3T3-E1) in vitro. Considering the long period of bone regeneration, to effectively exert the reparative effect of exosomes, we synthesized an injectable hydroxyapatite (HAP) embedded in situ cross-linked hyaluronic acid-alginate (HA-ALG) hydrogel system to durably retain exosomes at the defect sites. Then, we combined the exosomes with the HAP embedded in situ cross-linked HA-ALG hydrogel system to repair bone defects in rats in vivo. The results showed that the combination of exosomes and composite hydrogel could significantly enhance bone regeneration. Our experiment pr...