Hai-Guang Zhang, Department of Orthopaedics, Yantaishan Hospital, Yantaishan Hospital Affiliated to Binzhou Medical University, Yantai Key Laboratory for Repair and Reconstruction of Bone & Joint, No. 10087 Science and Technology Avenue, Laishan District, Yantai 264003, Shandong Province, China. zhg10087@163.com
Research Domain of This Article
Cell & Tissue Engineering
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Bo Cong, Feng-Hua Zhang, Hai-Guang Zhang, Department of Orthopaedics, Yantaishan Hospital, Yantaishan Hospital Affiliated to Binzhou Medical University, Yantai Key Laboratory for Repair and Reconstruction of Bone & Joint, Yantai 264003, Shandong Province, China
Author contributions: Cong B and Zhang FH designed, supervised and drafted the manuscript; Zhang HG contributed to the critical revision, writing - review & editing; All authors have read and approved the article.
Supported by Yantai Science and Technology Innovation Development Plan Project, No. 2023YD048.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hai-Guang Zhang, Department of Orthopaedics, Yantaishan Hospital, Yantaishan Hospital Affiliated to Binzhou Medical University, Yantai Key Laboratory for Repair and Reconstruction of Bone & Joint, No. 10087 Science and Technology Avenue, Laishan District, Yantai 264003, Shandong Province, China. zhg10087@163.com
Received: April 17, 2025 Revised: May 27, 2025 Accepted: July 8, 2025 Published online: September 26, 2025 Processing time: 161 Days and 2.2 Hours
Abstract
Articular cartilage damage caused by trauma or degenerative diseases such as osteoarthritis remains a major therapeutic challenge due to the tissue’s limited regenerative capacity. Traditional surgical interventions-including microfracture, autologous chondrocyte implantation, and osteochondral grafting-often result in the formation of biomechanically inferior fibrocartilage and fail to restore long-term joint function. In contrast, stem cell-based strategies have emerged as a promising approach for regenerating hyaline-like cartilage by combining the biological potential of mesenchymal stem cells and induced pluripotent stem cells with advances in tissue engineering. This review synthesizes the current understanding of cartilage structure and repair limitations, evaluates the regenerative potential of various stem cell sources, and highlights engineering innovations such as bioactive scaffolds, controlled growth factor delivery, and three-dimensional bioprinting. We also examine key preclinical studies and early-phase clinical trials demonstrating the safety and efficacy of stem cell-based therapies. Finally, we explore future directions, including gene editing, exosome-based therapeutics, and personalized regenerative strategies, that may address remaining translational barriers. Collectively, stem cell-centered approaches offer a transformative avenue toward durable, functional cartilage repair and hold strong potential for clinical application.
Core Tip: This review highlights the emerging role of stem cell-based strategies in articular cartilage regeneration. By integrating the biological potential of mesenchymal stem cells and induced pluripotent stem cells with engineering advances such as bioactive scaffolds, growth factor delivery, and three-dimensional bioprinting, these approaches aim to overcome the limitations of traditional therapies. We also discuss cutting-edge developments including gene editing and exosome-based therapeutics, offering new insights into personalized and durable cartilage repair solutions.
