AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB026130117
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RESEARCH ARTICLE

CGA–Eu nanozyme-functionalized 3D-printed scaffolds accelerate osteoporotic bone regeneration via ROS scavenging and angio-osteogenic modulation

Wenjie Zhao1,2† ,  Xinyu Ding1† ,  Shuai Chen1† ,  Jiachen Zhang1 ,  Yuqing Zhou1 ,  Miaochao Qin1 ,  Peng Ma1 ,  Pengfei Sun1 ,  Hao Chen1* ,  Wen Min1* ,  Junwu Wang1*
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1 Department of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
2 Department of Orthopedics, Northern Jiangsu People’s Hospital, Nanjing University, Yangzhou, Jiangsu, China
†These authors contributed equally to this work.
IJB, 026130117 https://doi.org/10.36922/IJB026130117
Received: 26 March 2026 | Revised: 5 May 2026 | Accepted: 7 May 2026 | Published online: 7 May 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Impaired bone regeneration in osteoporosis primarily stems from a local pathological microenvironment characterized by high levels of reactive oxygen species (ROS), which severely inhibits osteogenic differentiation and angiogenesis. To address this challenge, this study engineered a 3D-printed multifunctional composite scaffold consisting of an α-tricalcium phosphate/zinc oxide (α-TCP/ZnO) matrix loaded with chlorogenic acid–europium (CGA–Eu) metal-phenolic network nanoparticles. The incorporation of ZnO effectively buffered the acidity generated by α-TCP degradation, thereby maintaining a physiological pH environment favorable for regeneration. Furthermore, CGA–Eu endowed the scaffold with potent antioxidant capacity, enabling it to efficiently scavenge excessive ROS and significantly alleviate oxidative damage in vitro. Biological evaluations confirmed that the sustained release of Eu3+, Zn2+, and CGA cooperatively promoted osteogenic differentiation of bone marrow mesenchymal stem cells and angiogenic activity in human umbilical vein endothelial cells. In an ovariectomized rat cranial defect model, the composite scaffold effectively accelerated bone mass accumulation and enhanced angiogenesis. In conclusion, this dual microenvironment-regulating strategy, which integrates pH buffering, ROS scavenging, and sustained osteo-angiogenic ion delivery, offers a promising scaffold design for osteoporotic bone defect repair.

Graphical abstract
Keywords
3D bioprinting
Bone regeneration
Chlorogenic acid
Europium
Microenvironment remodeling
Funding
This research was supported by the third batch of Jiangsu Province Traditional Chinese Medicine Leading Talent Training Program (Jiangsu Traditional Chinese Medicine Science and Education [2023] No. 17).
Conflict of interest
The authors declare no conflicts of interest.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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