DataVXAdvanced SciencePaper
journal article·2026-07-08Open access

Biomimetic Gradient Hydrogels Regulate Osteochondral Regeneration Microenvironment Remodeling via Spatiotemporal Programming Engineering

Xiaolian Niu, Shengzhao Xiao, Di Huang, Xuesong Wang, Yanwei Cao, Xiaodan Sun, Nicholas Dunne, Xiaoming Li

Advanced Science
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Abstract

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.
Source: crossref · Quality: baseline

Research context

PolymersNanomaterialsBiomaterialsComposites

OpenAlex topics: Osteoarthritis Treatment and Mechanisms · Bone Tissue Engineering Materials · Hydrogels: synthesis, properties, applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Key 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

Department of Biomedical Engineering Research Center for Nano‐biomaterials & Regenerative Medicine College of Artificial Intelligence Taiyuan University of Technology Taiyuan China

Department of Orthodontics Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine College of Stomatology Shanghai Jiao Tong University National Center for Stomatology National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai Research Institute of Stomatology Shanghai China

Sports Medicine Service Beijing Jishuitan Hospital Capital Medical University Beijing China

Key Laboratory of Advanced Materials of Ministry of Education Tsinghua University Beijing China

Centre For Medical Engineering Research School of Mechanical and Manufacturing Engineering Dublin City University Dublin Ireland

Funding

National Natural Science Foundation of China · Natural Science Foundation of Beijing Municipality · China Postdoctoral Science Foundation · Fok Ying Tung Education Foundation · Higher Education Discipline Innovation Project

References (54)

Show source-provided references
1. 10.1126/science.ads996010.1126/science.ads9960 ↗
2. 10.1038/s41584‐025‐01257‐210.1038/s41584‐025‐01257‐2 ↗
3. Integrated Gradient Tissue‐Engineered Osteochondral Scaffolds: Challenges, Current Efforts and Future Perspectives10.1016/j.bioactmat.2022.06.011 ↗
4. 10.1021/acsnano.4c1196010.1021/acsnano.4c11960 ↗
5. 10.1038/nrrheum.2016.14810.1038/nrrheum.2016.148 ↗
6. 10.1021/acsnano.5c1269410.1021/acsnano.5c12694 ↗
7. 10.1016/j.biomaterials.2010.07.02210.1016/j.biomaterials.2010.07.022 ↗
8. 10.1021/acsnano.4c1798910.1021/acsnano.4c17989 ↗
9. 10.1016/j.matt.2025.10236610.1016/j.matt.2025.102366 ↗
10. 10.1186/ar450610.1186/ar4506 ↗
11. 10.1038/ncomms227110.1038/ncomms2271 ↗
12. 10.1002/adma.20242039410.1002/adma.202420394 ↗
13. 10.1007/s13238‐020‐00692‐z10.1007/s13238‐020‐00692‐z ↗
14. 10.1016/j.actbio.2017.01.03610.1016/j.actbio.2017.01.036 ↗
15. 10.1038/nmat448910.1038/nmat4489 ↗
16. 10.1038/s41563‐019‐0458‐510.1038/s41563‐019‐0458‐5 ↗
17. 10.1002/adma.20160233210.1002/adma.201602332 ↗
18. 10.1002/adma.20200200810.1002/adma.202002008 ↗
19. 10.1002/anie.20150295710.1002/anie.201502957 ↗
20. 10.1002/adfm.20250394810.1002/adfm.202503948 ↗
21. 10.1016/j.tips.2014.03.00510.1016/j.tips.2014.03.005 ↗
22. Recapitulating Bone Development through Engineered Mesenchymal Condensations and Mechanical Cues for Tissue Regeneration10.1126/scitranslmed.aav7756 ↗
23. 10.1002/jor.2032910.1002/jor.20329 ↗
24. 10.1089/ten.tea.2013.004710.1089/ten.tea.2013.0047 ↗
25. 10.1126/sciadv.adc922210.1126/sciadv.adc9222 ↗
26. 10.1002/adma.20170125510.1002/adma.201701255 ↗
27. 10.1002/advs.20190339510.1002/advs.201903395 ↗
28. 10.1016/j.biomaterials.2019.11964510.1016/j.biomaterials.2019.119645 ↗
29. 10.1002/advs.20220077510.1002/advs.202200775 ↗
30. 10.1016/j.jconrel.2024.08.01110.1016/j.jconrel.2024.08.011 ↗
31. 10.1016/j.actbio.2023.03.04510.1016/j.actbio.2023.03.045 ↗
32. 10.1016/j.actbio.2021.03.05710.1016/j.actbio.2021.03.057 ↗
33. 10.1016/j.biomaterials.2018.08.04410.1016/j.biomaterials.2018.08.044 ↗
34. 10.1016/j.biomaterials.2021.12083810.1016/j.biomaterials.2021.120838 ↗
35. 10.1002/adfm.20200013010.1002/adfm.202000130 ↗
36. A Cellularized Biphasic Implant Based on a Bioactive Silk Fibroin Promotes Integration and Tissue Organization during Osteochondral Defect Repair in a Porcine Model10.3390/ijms20205145 ↗
37. 10.1002/adhm.20190142310.1002/adhm.201901423 ↗
38. 10.1002/adfm.20140082810.1002/adfm.201400828 ↗
39. 10.1126/sciadv.abd821710.1126/sciadv.abd8217 ↗
40. 10.1016/j.biomaterials.2018.02.01010.1016/j.biomaterials.2018.02.010 ↗
41. 10.1016/j.actbio.2024.06.02710.1016/j.actbio.2024.06.027 ↗
42. 10.1038/ni137310.1038/ni1373 ↗
43. 10.1002/adma.20241554310.1002/adma.202415543 ↗
44. 10.1038/nri308810.1038/nri3088 ↗
45. 10.1089/ten.tea.2017.023210.1089/ten.tea.2017.0232 ↗
46. 10.1016/j.ijbiomac.2025.14754110.1016/j.ijbiomac.2025.147541 ↗
47. 10.1038/ncomms736510.1038/ncomms7365 ↗
48. 10.1016/j.ijbiomac.2024.13760210.1016/j.ijbiomac.2024.137602 ↗
49. 10.1080/17425247.2019.163511610.1080/17425247.2019.1635116 ↗
50. Inflammation, Fracture and Bone Repair10.1016/j.bone.2016.02.020 ↗
51. 10.1038/s41467‐021‐27816‐110.1038/s41467‐021‐27816‐1 ↗
52. Repair of Osteochondral Defects: Efficacy of a Tissue‐Engineered Hybrid Implant Containing both Human MSC and Human iPSC‐Cartilaginous Particles10.1038/s41536-023-00335-x ↗
53. In‐Situ Forming Injectable GFOGER‐Conjugated BMSCs‐Laden Hydrogels for Osteochondral Regeneration10.1038/s41536-022-00274-z ↗
54. 10.1016/j.joca.2016.10.01410.1016/j.joca.2016.10.014 ↗