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Updated: Jun 9, 2025
The Synthesis of RGD-functionalized Hydrogels as a Tool for Therapeutic Applications
Published on: October 7, 2016
A Single-Cell RNA Sequencing Guided Multienzymatic Hydrogel Design for Self-Regenerative Repair in Diabetic
Peihua Lin1,2, Zhouyang Qian3, Shanbiao Liu4
1Frontiers 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.
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.
