Integration of Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomes with Hydroxyapatite-Embedded Hyaluronic Acid-Alginate Hydrogel for Bone Regeneration

Abstract

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-derived exosomes could effectively promote the proliferation, migration, and osteogenic differentiation of a murine calvariae preosteoblast cell line 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 provides a new strategy for exosome-based therapy, which shows great potential in future tissue and organ repair.