AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB025120100
REVIEW ARTICLE

Hierarchical 3D-printed scaffolds for osteochondral regeneration: From biomimetic design to functional integration

Qi Wang1 Wei Zhu1 Ruoying Wang1 Xisheng Weng1*
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1 Department of Orthopedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100730 Beijing, China
Received: 22 March 2025 | Accepted: 28 April 2025 | Published online: 28 April 2025
© 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/ )
Abstract

Osteochondral defects, characterized by the structural and functional disruption of articular cartilage and subchondral bone, present significant clinical challenges due to the tissue’s limited intrinsic regenerative capacity. Scaffold-based tissue engineering has paved the way for osteochondral defect treatment; however, fully restoring the complex structure and composition of native osteochondral tissue remains challenging. Recent advances in three-dimensional (3D) printing have enabled the fabrication of layered, anisotropic scaffolds designed to biomimetically recapitulate the native tissue’s zonal properties through precise hierarchical design. High-resolution fabrication techniques facilitate the construction of delicate microarchitectures, while advanced bioprinting methods allow for the incorporation of bioactive factors and cells into the scaffold matrix. This review emphasizes the following four scaffold design paradigms: composite gradients, microarchitectural patterning, biochemical gradients, and cellular heterogeneity. Moreover, key properties of multilayered scaffolds are discussed, including mechanical performance, interfacial strength, and degradation behavior. In addition, several obstacles associated with the in vivo scaffold application are discussed, providing insights to guide future clinical translation in osteochondral defects treatment.  

Graphical abstract
Keywords
3D-printed scaffold
Biomaterials
Osteoarthritis
Osteochondral regeneration
Regenerative medicine
Tissue engineering
Funding
This work was supported by the Natural Science Foundation of Beijing, China (Grant No. 7232119), the Beijing Natural Science Foundation (Grant No. L232006), Peking Union Medical College Hospital Talent Cultivation Program (Grant No. UHB11847), the National High Level Hospital Clinical Research Funding (No. 2022-PUMCH-C-036), and the National Natural Science Foundation Youth Fund (Grant No. 82102582).
Conflict of interest
The authors declare no competing interests.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing