A Factor-Free Hydrogel with ROS Scavenging and Responsive Degradation for Enhanced Diabetic Bone Healing

Qin Zhang; Weikai Chen; Guangfeng Li; Zhixin Ma; Mengru Zhu; Qianmin Gao; Ke Xu; Xinru Liu; Wenyi Lu; Wencai Zhang; Yan Wu; Zhongmin Shi; Jiacan Su

doi:10.1002/smll.202306389

A Factor-Free Hydrogel with ROS Scavenging and Responsive Degradation for Enhanced Diabetic Bone Healing

Small. 2024 Jan 2:e2306389. doi: 10.1002/smll.202306389. Online ahead of print.

Authors

Qin Zhang^{1

2

3}, Weikai Chen⁴, Guangfeng Li⁵, Zhixin Ma^{1

2

3}, Mengru Zhu^{1

2

3}, Qianmin Gao^{1

2

3}, Ke Xu^{1

2

3}, Xinru Liu^{1

2

3}, Wenyi Lu⁶, Wencai Zhang⁷, Yan Wu^{1

2

3}, Zhongmin Shi^{8

9}, Jiacan Su^{1

2

3

10}

Affiliations

¹ Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
² Organoid Research Center, Shanghai University, Shanghai, 200444, China.
³ National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China.
⁴ Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hosptial of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
⁵ Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai, 200941, China.
⁶ Binzhou Institute of Technology, Binzhou, Shandong, 256606, China.
⁷ Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510630, China.
⁸ National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, 200233, China.
⁹ Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai, 200233, China.
¹⁰ Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

PMID: 38168513
DOI: 10.1002/smll.202306389

Abstract

In view of the increased levels of reactive oxygen species (ROS) that disturb the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), the repair of diabetic bone defects remains a great challenge. Herein, a factor-free hydrogel is reported with ROS scavenging and responsive degradation properties for enhanced diabetic bone healing. These hydrogels contain ROS-cleavable thioketal (TK) linkers and ultraviolet (UV)-responsive norbornene (NB) groups conjugated with 8-arm PEG macromers, which are formed via UV crosslinking-mediated gelation. Upon reacting with high levels of ROS in the bone defect microenvironment, ROS-cleavable TK linkers are destroyed, allowing the responsive degradation of hydrogels, which promotes the migration of BMSCs. Moreover, ROS levels are reduced through hydrogel-mediated ROS scavenging to reverse BMSC differentiation from adipogenic to osteogenic phenotype. As such, a favorable microenvironment is created after simultaneous ROS scavenging and hydrogel degradation, leading to the effective repair of bone defects in diabetic mouse models, even without the addition of growth factors. Thus, this study presents a responsive hydrogel platform that regulates ROS scavenging and stromal degradation in bone engineering.

Keywords: bone marrow mesenchymal stem cells; diabetic bone healing; hydrogels; osteogenic differentiation; reactive oxygen species.

Abstract

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