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  3. A Single-Cell RNA Sequencing Guided Multienzymatic Hydrogel Design for Self-Regenerative Repair in Diabetic Mandibular Defects

A Single-Cell RNA Sequencing Guided Multienzymatic Hydrogel Design for Self-Regenerative Repair in Diabetic Mandibular Defects

  • Adv Mater. 2024 Dec;36(50):e2410962. doi: 10.1002/adma.202410962.
Peihua Lin 1 2,  Zhouyang Qian 3,  Shanbiao Liu 4,  Xin Ye 3,  Pengpeng Xue 4,  Yangjie Shao 3,  Jing Zhao 4,  Yunan Guan 4,  Zhichao Liu 3,  Yuhua Chen 3,  Qiyue Wang 1,  Zhigao Yi 5,  Mingjian Zhu 4,  Mengfei Yu 3,  Daishun Ling 1,  Fangyuan Li 2
Affiliations

Affiliations

  • 1 Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, School of Biomedical Engineering, National Center for Translational Medicine, Zhang Jiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • 2 Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders (LEAD), Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, China.
  • 3 Key Laboratory of Oral Biomedical Research of Zhejiang Province, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, China.
  • 4 Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
  • 5 Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science (CAS), Suzhou, 215163, China.
PMID: 39436107 DOI: 10.1002/adma.202410962
Abstract

Conventional bone tissue engineering Materials struggle to reinstate physiological bone remodeling in a diabetic context, primarily due to the compromised repolarization of proinflammatory macrophages to anti-inflammatory macrophages. Here, leveraging single-cell RNA Sequencing (scRNA-seq) technology, the pivotal role of nitric oxide (NO) and Reactive Oxygen Species (ROS) is unveiled in impeding macrophage repolarization during physiological bone remodeling amidst diabetes. Guided by scRNA-seq analysis, we engineer a multienzymatic bone tissue engineering hydrogel scaffold (MEBTHS) composed is engineered of methylpropenylated gelatin hydrogel integrated with ruthenium nanozymes, possessing both Ru0 and Ru4+ components. This design facilitates efficient NO elimination via Ru0 while simultaneously exhibiting ROS scavenging properties through Ru4+. Consequently, MEBTHS orchestrates macrophage reprogramming by neutralizing ROS and reversing NO-mediated Mitochondrial Metabolism, thereby rejuvenating bone marrow-derived mesenchymal stem cells and endothelial cells within diabetic mandibular defects, producing newly formed bone with quality comparable to that of normal bone. The scRNA-seq guided multienzymatic hydrogel design fosters the restoration of self-regenerative repair, marking a significant advancement in bone tissue engineering.

Keywords

Ru nanozyme; diabetic mandibular defects; multienzymatic hydrogel; self‐regenerative repair; single‐cell RNA sequencing.

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