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On-line Access: 2025-10-27

Received: 2025-05-14

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Journal of Zhejiang University SCIENCE B

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Single-cell RNA sequencing guided reactive oxygen species scavenging hydrogel design for regeneration of osteoporotic bone


Author(s):  Wei HU1*, Tianyi FEI2*, Zhichao LIU2, Yude DING1, Mengfei YU2, Fan YANG1, Feiya ZHAO1

Affiliation(s):  1Center for Plastic & Reconstructive Surgery, Department of Stomatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China 2Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310017, China

Corresponding email(s):  Feiya ZHAO, zhaofeiya@hmc.edu.cn Fan YANG, yangfan@hmc.edu.cn

Key Words:  Osteoporosis; Single-cell RNA sequencing; Reactive oxygen species (ROS); Curcumin (CCM); Bone regeneration


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Wei HU1*, Tianyi FEI2*, Zhichao LIU2, Yude DING1, Mengfei YU2, Fan YANG1, Feiya ZHAO1. Single-cell RNA sequencing guided reactive oxygen species scavenging hydrogel design for regeneration of osteoporotic bone[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2500254

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author="Wei HU1*, Tianyi FEI2*, Zhichao LIU2, Yude DING1, Mengfei YU2, Fan YANG1, Feiya ZHAO1",
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doi="https://doi.org/10.1631/jzus.B2500254"
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Abstract: 
The pathological microenvironment of osteoporosis poses a substantial clinical challenge for bone defect regeneration. Through single-cell RNA sequencing (scRNA-seq) analysis, we identified a reactive oxygen species (ROS)-overloading osteoblast subpopulation as a critical pathological feature of osteoporotic niches. Guided by scRNA-seq analysis, we engineered a microenvironment-adaptive hydrogel system through precise integration of antioxidant curcumin-encapsulated zeolitic imidazolate framework-8 nanoparticles (CCM@ZIF-8 NPs) within photo-crosslinkable alginate methacrylate (AlgMA) hydrogel (AlgMA/CCM@ZIF-8). This engineered design exhibited dual functions: effectively scavenging ROS in bone marrow-derived mesenchymal stem cells (BMSCs) while simultaneously suppressing osteoclast differentiation. The osteo-regenerative superiority of the AlgMA/CCM@ZIF-8 nanocomposite hydrogel was conclusively demonstrated in bone defect models of osteoporotic mice. This scRNA-seq-informed engineering strategy offers a promising approach for developing pathophysiology-adapted biomaterials to promote regenerative repair in osteoporotic bone defects.

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