Exosome-loaded extracellular matrix-mimic hydrogel with anti-inflammatory property Facilitates/promotes growth plate injury repair

Pengfei Guan; Can Liu; Denghui Xie; Shichao Mao; Yuelun Ji; Yongchang Lin; Zheng Chen; Qiyou Wang; Lei Fan; Yongjian Sun

doi:10.1016/j.bioactmat.2021.09.010

Exosome-loaded extracellular matrix-mimic hydrogel with anti-inflammatory property Facilitates/promotes growth plate injury repair

Bioact Mater. 2021 Sep 16:10:145-158. doi: 10.1016/j.bioactmat.2021.09.010. eCollection 2022 Apr.

Authors

Pengfei Guan¹, Can Liu², Denghui Xie³, Shichao Mao¹, Yuelun Ji¹, Yongchang Lin¹, Zheng Chen⁴, Qiyou Wang⁵, Lei Fan⁶, Yongjian Sun¹

Affiliations

¹ Department of Pediatric Orthopedic, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510515, China.
² Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
³ Department of Joint Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510515, China.
⁴ Department of Stomatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
⁵ Department of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, 510515, China.
⁶ Department of Orthopedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

Abstract

Growth plate cartilage has limited self-repair ability, leading to poor bone bridge formation post-injury and ultimately limb growth defects in children. The current corrective surgeries are highly invasive, and outcomes can be unpredictable. Following growth plate injury, the direct loss of extracellular matrix (ECM) coupled with further ECM depletion due to the inhibitory effects of inflammation on the cartilage matrix protein greatly hinder chondrocyte regeneration. We designed an exosome (Exo) derived from bone marrow mesenchymal stem cells (BMSCs) loaded ECM-mimic hydrogel to promote cartilage repair by directly supplementing ECM and anti-inflammatory properties. Aldehyde-functionalized chondroitin sulfate (OCS) was introduced into gelatin methacryloyl (GM) to form GMOCS hydrogel. Our results uncovered that GMOCS hydrogel could significantly promote the synthesis of ECM due to the doping of OCS. In addition, the GMOCS-Exos hydrogel could further promote the anabolism of chondrocytes by inhibiting inflammation and ultimately promote growth plate injury repair through ECM remodeling.

Keywords: Exosomes; Extracellular matrix deposition; Extracellular matrix-mimic hydrogel; Growth plate injury repair; Immunomodulatory.