Multifaceted Catalytic Glucose Depletion and Reactive Oxygen Species-Scavenging Nanoenzyme Composite Hydrogel for Facilitating Diabetic Bone Regeneration
Abstract
Regeneration of diabetic bone defects remains a formidable challenge due to the chronic hyperglycemic state, which triggers the accumulation of advanced glycation end products (AGEs) and reactive oxygen species (ROS). To address this issue, we have engineered a bimetallic metal–organic framework-derived Mn@Co 3 O 4 @Pt nanoenzyme loaded with alendronate and Mg 2+ ions (termed MCPtA) to regulate the hyperglycemic microenvironment and recover the osteogenesis/osteoclast homeostasis. Notably, the Mn atom substitution in the Co 3 O 4 nanocrystalline structure could modulate the electronic structure and significantly improve the SOD/CAT catalytic activity for ROS scavenging. By integration with GOx-like Pt nanoparticles, the MCPtA achieved effective multiple cascade catalytic performance that facilitated the clearance of glucose and ROS. Furthermore, the MCPtA was encapsulated within a glucose-responsive hydrogel cross-linked via a borate ester bond, termed PAM, to evaluate the potential of the composite hydrogel for cranial defect repair in diabetic rats. The in vitro/vivo experiments as well as the RNA sequencing analysis demonstrated that the nanoenzyme composite hydrogel could disrupt the glucose-ROS-induced inflammation and promoted osteogenesis and angiogenesis, in consequence, improving the therapeutic effects for diabetic bone regeneration. This study provided crucial insights into nanoenzyme-mediated microenvironmental regulation for diabetic bone regeneration.
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The imbalance between osteoblast and osteoclast activity complicates bone defect repair in DM.
“The imbalance between osteoblast and osteoclast activity further complicates bone defect repair in DM9,10.”
From Microenvironment-responsive multifunctional enzyme-linked hydrogel for diabetic bone defect regeneration. (2025) · cites this paper as [10]
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Fu, X., Luo, Z., Guo, Y., Meng, W., Jin, S., Chen, J., Cai, Y., Luo, Z., Huang, C., Chen, A., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-65165-5 · Cited by 44 · see citing works
“The imbalance between osteoblast and osteoclast activity further complicates bone defect repair in DM 9,10 .”
- Authors
- Liu, S., Lu, M., Zhang, M., Sun, X., Luo, B., & Wu, Y.
- Affiliations
- Sichuan University (CN)
- Corresponding author
- Luo, Bin
- Wu, Yao
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2025-01-09
- Volume
- 19
- Issue
- 2
- Pages
- 2677-2694
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- OpenAlex
- W4406220530
- Cited by
- 90
- References
- 49
- Citations by year
- 2026: 47 · 2025: 43
- FWCI
- 21.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Nano (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundamental Research Funds for the Central Universities
- Major State Basic Research Development Program of China (2022YFC2406102)
- National Natural Science Foundation of China (32271394)
- Sichuan Province Innovative Talent Funding Project for Postdoctoral Fellows
- Sichuan International Science and Technology Innovation Cooperation (2024YFHZ0352)
- Hong Kong Macao Taiwan Science and Technology Innovation Cooperation Project (2024YFHZ0352)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Physical Sciences › Materials Science › Materials Chemistry › Advanced Nanomaterials in Catalysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- nanozymes, glucose depletion, reactive oxygen species scavenging, advanced glycation end products, hyperglycemia, metal-organic frameworks, alendronate, Mg2+ ions, glucose-responsive hydrogels, cranial defect repair, bone formation, angiogenesis, inflammation, bone microenvironment
- MeSH terms
- RAW 264.7 Cells, Metal-Organic Frameworks, Animals, Bone Regeneration, Catalysis, Diabetes Mellitus, Experimental, Glucose, Male, Osteogenesis, Free Radical Scavengers, Rats, Sprague-Dawley, Reactive Oxygen Species, Alendronate, Hydrogels, Mice, Rats
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