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Updated: Jul 10, 2026

Integrated Bone Formation Through In Vivo Endochondral Ossification Using Mesenchymal Stem Cells
Published on: July 14, 2023
Biomimetic Gradient Hydrogels Regulate Osteochondral Regeneration Microenvironment Remodeling via Spatiotemporal
Xiaolian Niu1,2, Shengzhao Xiao3, Di Huang2
1Key Laboratory For Biomechanics and Mechanobiology of Ministry of Education, Key Laboratory of Innovation and Transformation of Advanced Medical Devices of Ministry of Industry and Information Technology, National Medical Innovation Platform for Industry-Education Integration in Advanced Medical Devices (Interdiscipline of Medicine and Engineering), Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
Abstract:
Osteochondral repair remains a critical challenge owing to conventional scaffolds' inadequate dynamic mechanical adaptability, poor interfacial integration, inefficient cell recruitment, and lack of spatiotemporal regulation of bioactive cues. Inspired by native tissue hierarchical gradients and endogenous healing mechanisms, we developed an electric field-driven continuous gradient hydrogel (GHZF4) via spatiotemporal programming. Integrating nanofiber-reinforced self-adaptive matrix, electric field-induced nanofiber alignment, and ZIF-8 nanocarrier-mediated bioactive release, GHZF4 constructs compositional/structural/mechanical gradients. Its bone-mimetic zone achieves burst release of PDGF-BB and sustained release of BMP-2 for vascularized osteogenesis, while the cartilage-mimetic zone sustains TGF-β3 release for chondrogenesis. In vitro, GHZF4 enhances macrophage M2 polarization, autologous stem cell recruitment, angiogenesis, and osteochondral differentiation. In rat/rabbit defect models, it enables seamless integration and functional repair, validated by micro-CT, nanoindentation and histology. Transcriptomic analysis reveals the potential upregulation of signaling pathways associated with immunomodulation, angiogenesis, and osteochondral differentiation, which shows strong consistency with our in vitro functional outcomes and in vivo regenerative phenotypes. This nanofunctionalized gradient scaffold spatiotemporally couples key repair processes, providing a promising proof-of-concept strategy for cell-free functional osteochondral repair.

