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

Wei Lu; Min Zeng; Wenbin Liu; Tianliang Ma; Xiaolei Fan; Hui Li; Yinan Wang; Haoyi Wang; Yihe Hu; Jie Xie

doi:10.1016/j.mtbio.2023.100569

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

Mater Today Bio. 2023 Feb 1:19:100569. doi: 10.1016/j.mtbio.2023.100569. eCollection 2023 Apr.

Authors

Wei Lu^{1

2}, Min Zeng^{1

2}, Wenbin Liu^{1

2}, Tianliang Ma^{1

2}, Xiaolei Fan³, Hui Li⁴, Yinan Wang^{1

2}, Haoyi Wang^{1

2}, Yihe Hu^{1

4}, Jie Xie^{1

4}

Affiliations

¹ Department of Orthopedic Surgery, National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
² Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Changsha, China.
³ Department of Orthopedics, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.
⁴ Department of Orthopedics, The First Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China.

Abstract

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.

Keywords: Bone regeneration; Exosomes; GelMA; H-type vessels; HAMA.