<br>具有 ROS 清除和响应性降解功能的无因子水凝胶，可增强糖尿病骨愈合,Small

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具有 ROS 清除和响应性降解功能的无因子水凝胶，可增强糖尿病骨愈合
Small ( IF 13.0 ) Pub Date : 2024-01-02 , DOI: 10.1002/smll.202306389
Qin Zhang _{1,

2,

3} , Weikai Chen ₄ , Guangfeng Li ₅ , 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 Lu ₆ , Wencai Zhang ₇ , Yan Wu _{1,

2,

3} , Zhongmin Shi _{8,

9} , Jiacan Su _{1,

2,

3,

10}

Affiliation

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

鉴于活性氧（ROS）水平升高会干扰骨髓间充质干细胞（BMSC）的成骨分化，糖尿病骨缺损的修复仍然是一个巨大的挑战。本文报道了一种无因子水凝胶，其具有 ROS 清除和响应性降解特性，可增强糖尿病骨愈合。这些水凝胶含有 ROS 可裂解的硫缩酮 (TK) 连接体和与 8 臂 PEG 大分子偶联的紫外线 (UV) 响应性降冰片烯 (NB) 基团，这些基团是通过紫外线交联介导的凝胶化形成的。与骨缺损微环境中高水平的 ROS 发生反应后，ROS 可裂解的 TK 连接子被破坏，从而使水凝胶发生响应性降解，从而促进 BMSC 的迁移。此外，通过水凝胶介导的ROS清除来降低ROS水平，从而逆转BMSC从成脂表型向成骨表型的分化。因此，在同时进行ROS清除和水凝胶降解后，会产生有利的微环境，从而即使不添加生长因子，也能有效修复糖尿病小鼠模型中的骨缺损。因此，本研究提出了一种响应性水凝胶平台，可调节骨工程中的 ROS 清除和基质降解。

"点击查看英文标题和摘要"

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

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.

更新日期：2024-01-02

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