Human urine-derived stem cell exosomes delivered via injectable GelMA templated hydrogel accelerate bone regeneration

The key to critical bone regeneration in tissue engineering relies on an ideal bio-scaffold coated with a controlled release of growth factors. Gelatin methacrylate (GelMA) and Hyaluronic acid methacrylate (HAMA) have been a novel topic of interest in bone regeneration while introducing appropriate nano-hydroxyapatite (nHAP) to improve its mechanical properties. And the exosomes derived from human urine-derived stem cells (human USCEXOs) have also been reported to promote osteogenesis in tissue engineering. The present study aimed to design a new GelMA-HAMA/nHAP composite hydrogel as a drug delivery system. The USCEXOs were encapsulated and slow-released in the hydrogel for better osteogenesis. The characterization of the GelMA-based hydrogel showed excellent controlled release performance and appropriate mechanical properties. The in vitro studies showed that the USCEXOs/GelMA-HAMA/nHAP composite hydrogel could promote the osteogenesis of bone marrow mesenchymal stem cells (BMSCs) and the angiogenesis of endothelial progenitor cells (EPCs), respectively. Meanwhile, the in vivo results confirmed that this composite hydrogel could significantly promote the defect repair of cranial bone in the rat model. In addition, we also found that USCEXOs/GelMA-HAMA/nHAP composite hydrogel can promote the formation of H-type vessels in the bone regeneration area, enhancing the therapeutic effect. In conclusion, our findings suggested that this controllable and biocompatible USCEXOs/GelMA-HAMA/nHAP composite hydrogel may effectively promote bone regeneration by coupling osteogenesis and angiogenesis.