AccScience Publishing / IJB / Volume 11 / Issue 1 / DOI: 10.36922/ijb.5104
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RESEARCH ARTICLE

Biomimetically hierarchical scaffolds drive critical-sized osteochondral tissue regeneration

Farnaz Ghorbani1,2,3* ,  Joaquim Miguel Oliveira4,5* ,  Zhi Qian1,6 ,  Chongjing Zhang2 ,  Yi Zhang7 ,  Behafarid Ghalandari8 ,  Dejian Li2 ,  Zeyuan Zhong2,9 ,  Zichen Liu2,10 ,  Yuanyuan Liu7,11,12 ,  Baoqing Yu1*
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1 Department of Orthopaedics, Seventh People’s Hospital of Shanghai, University of Traditional Chinese Medicine, Shanghai, China
2 Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
3 Department of Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
4 3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, Guimarães, Portugal
5 ICVS/3B’s–PT Government Associate Laboratory, Braga, Guimarães, Portugal
6 Department of Orthopaedics, Institute of Bone and Joint Disease, Zhangye People’s Hospital affiliated to Hexi University, Gansu, China
7 School of Mechatronic Engineering and Automation, Shanghai University, Shanghai, China
8 Division of Surgery and Interventional Science, Department of Surgical Biotechnology, University College London, London, United Kingdom
9 Department of Orthopedics, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
10 Department of Materials Science and Engineering, School of Materials Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
11 National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, China
12 Wenzhou Institute of Shanghai University, Wenzhou, Zhejiang, China
IJB 2025, 11(1), 573–597; https://doi.org/10.36922/ijb.5104
Submitted: 9 October 2024 | Accepted: 7 January 2025 | Published: 7 January 2025
(This article belongs to the Special Issue Bioprinting of in Vitro Tissue and Disease Models)
© 2025 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

This study presents a pioneering approach utilizing hierarchically functionalized scaffolds to foster anisotropic osteochondral tissue regeneration, leveraging the integration of distinct yet interconnected layers. We developed 3D-printed polydopamine-modified polycaprolactone (PCL) scaffolds, which were subsequently covered with a layer of electrospun PCL-gelatin fibers, and then functionalized with gelatin-bone morphogenetic protein-2 (BMP-2) following oxygen plasma surface treatments, creating a hierarchically organized multi-phasic architecture. This interconnected porous microstructure enabled controllable degradation while maintaining mechanical integrity and hydroxyapatite mineralization. In vitro assessments demonstrated that the scaffolds provided superior support for rat bone marrow mesenchymal stem cells, marked by their enhanced adhesion, viability, and proliferation. Increased alkaline phosphatase activity and osteocalcin expression over 14 days indicated that the scaffolds enhanced osteogenic performance, likely due to BMP-2 interaction with serum proteins, as supported by simulation studies, augmenting growth factor bioavailability. In vivo investigations in rabbit critical- sized osteochondral defects at 4- and 12-week post-implantation demonstrated that the multi-phasic scaffolds notably promoted secretion of type I and II collagen, neo-tissue formation, and integration with surrounding tissue, with significant results observed at 12 weeks. These findings indicate the potential of multi-phasic scaffolds for osteochondral tissue regeneration.

Graphical abstract
Keywords
3D printing
Biomimetic scaffolds
Electrospinning
Hierarchical scaffolds
Osteochondral tissue
Tissue engineering
Funding
This work was supported by the new quality specialty program of peak plateau clinical medicine of Pudong new area health commission (2024-PWXZ-21); the Program of key medicine of Shanghai Municipal Health Commission (2024ZDXK0038); the Demonstration pilot project of central financial support for the inheritance and innovation of traditional Chinese medicine (YC-2023-0202).
Conflict of interest
Joaquim Miguel Oliveira serves as the Editorial Board Member of the journal and the guest editor of the special issue: Bioprinting of In Vitro Tissue and Disease Models, but did not in any way involve in the editorial and peer-review process conducted for this paper, directly or indirectly. The authors have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript. The authors declare they have no competing interests.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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