Page 12 - v11i4

International

Journal of Bioprinting

REVIEW ARTICLE
Hierarchical 3D-printed scaffolds for

osteochondral regeneration: From biomimetic
design to functional integration

Qi Wang , Wei Zhu , Ruoying Wang , and Xisheng Weng* id
id
id
id
Department of Orthopedics, Peking Union Medical College Hospital, Chinese Academy of Medical
Sciences & Peking Union Medical College, 100730 Beijing, China
(This article belongs to the Special Issue: Advances in Bioprinting and Organ-on-a-chip and Applications for
Precision Medicine)

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
*Corresponding author: following four scaffold design paradigms: composite gradients, microarchitectural
Xisheng Weng patterning, biochemical gradients, and cellular heterogeneity. Moreover,
(xshweng@medmail.com.cn)
key properties of multilayered scaffolds are discussed, including mechanical
Citation: Weng X, Wang R, Zhu W, performance, interfacial strength, and degradation behavior. In addition, several
Wang Q. Hierarchical 3D-printed obstacles associated with the in vivo scaffold application are discussed, providing
scaffolds for osteochondral
regeneration: From biomimetic insights to guide future clinical translation in osteochondral defects treatment.
design to functional integration.
Int J Bioprint. 2025;11(4):4-31.
doi: 10.36922/IJB025120100 Keywords: 3D-printed scaffold; Biomaterials; Osteoarthritis; Osteochondral
Received: March 22, 2025 regeneration; Regenerative medicine; Tissue engineering
Revised: April 16, 2025
Accepted: April 28, 2025
Published online: April 28, 2025
Copyright: © 2025 Author(s). 1. Introduction
This is an Open Access article
distributed under the terms of the Osteochondral defect, caused by injury or various forms of arthritis including
Creative Commons Attribution osteoarthritis (OA), imposes a growing global health burden. Over 500 million
1,2
License, permitting distribution, 3
and reproduction in any medium, individuals worldwide are suffering from OA, making it the seventh leading cause of
4
provided the original work is disability. Notably, early-onset OA (diagnosed before the age of 55) accounts for over
properly cited. 50% of new cases, indicating a growing trend of osteochondral injuries occurring in
5
Publisher’s Note: AccScience younger populations. Unfortunately, osteochondral tissue has limited self-healing
Publishing remains neutral with capability due to cartilage avascularity. Current therapeutic approaches include the
6
regard to jurisdictional claims in
published maps and institutional following: (1) palliative treatment, such as topical or oral administration of non-steroidal
affiliations. anti-inflammatory drugs (NSAIDs), corticosteroid intra-articular injections, or physical

Volume 11 Issue 4 (2025) 4 doi: 10.36922/IJB025120100