Advancements in chondrocyte 3-dimensional embedded culture: Implications for tissue engineering and regenerative medicine

Cartilage repair necessitates regenerative medicine because of the unreliable healing mechanism of cartilage. To yield a sufficient number of cells for transplantation, chondrocytes must be expanded in culture. However, in 2D culture, chondrocytes tend to lose their distinctive phenotypes and functi...

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Main Authors: Yu-Ying Chu, Atsuhiko Hikita, Yukiyo Asawa, Kazuto Hoshi
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Biomedical Journal
Online Access:http://www.sciencedirect.com/science/article/pii/S2319417024000891
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author Yu-Ying Chu
Atsuhiko Hikita
Yukiyo Asawa
Kazuto Hoshi
author_facet Yu-Ying Chu
Atsuhiko Hikita
Yukiyo Asawa
Kazuto Hoshi
author_sort Yu-Ying Chu
collection DOAJ
description Cartilage repair necessitates regenerative medicine because of the unreliable healing mechanism of cartilage. To yield a sufficient number of cells for transplantation, chondrocytes must be expanded in culture. However, in 2D culture, chondrocytes tend to lose their distinctive phenotypes and functionalities after serial passage, thereby limiting their efficacy for tissue engineering purposes.The mechanism of dedifferentiation in 2D culture can be attributed to various factors, including abnormal nuclear strength, stress-induced mitochondrial impairment, chromatin remodeling, ERK-1/2 and the p38/mitogen-activated protein kinase (MAPK) signaling pathway. These mechanisms collectively contribute to the loss of chondrocyte phenotype and reduced production of cartilage-specific extracellular matrix (ECM) components.Chondrocyte 3D culture methods have emerged as promising solutions to prevent dedifferentiation. Techniques, such as scaffold-based culture and scaffold-free approaches, provide chondrocytes with a more physiologically relevant environment, promoting their differentiation and matrix synthesis. These methods have been used in cartilage tissue engineering to create engineered cartilage constructs for transplantation and joint repair.However, chondrocyte 3D culture still has limitations, such as low viability and proliferation rate, and also difficulties in passage under 3D condition. These indicate challenges of obtaining a sufficient number of chondrocytes for large-scale tissue production. To address these issues, ongoing studies of many research groups have been focusing on refining culture conditions, optimizing scaffold materials, and exploring novel cell sources such as stem cells to enhance the quality and quantity of engineered cartilage tissues.Although obstacles remain, continuous endeavors to enhance culture techniques and overcome limitations offer a promising outlook for the advancement of more efficient strategies for cartilage regeneration.
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spelling doaj-art-ab1f8ec3dd6e440dbab1735e4ed5f0952025-08-20T03:25:04ZengElsevierBiomedical Journal2319-41702025-04-0148210078610.1016/j.bj.2024.100786Advancements in chondrocyte 3-dimensional embedded culture: Implications for tissue engineering and regenerative medicineYu-Ying Chu0Atsuhiko Hikita1Yukiyo Asawa2Kazuto Hoshi3Department of Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Plastic and Reconstructive Surgery, Craniofacial Research Centre, Chang Gung Memorial Hospital at Linko, College of Medicine, Chang Gung University, Taoyuan, TaiwanDepartment of Tissue Engineering, The University of Tokyo Hospital, Tokyo, JapanDepartment of Tissue Engineering, The University of Tokyo Hospital, Tokyo, JapanDepartment of Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Tissue Engineering, The University of Tokyo Hospital, Tokyo, Japan; Corresponding author. Department of Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, Department of Oral-maxillofacial Surgery, Dentistry and Orthodontics Division of Tissue Engineering, The University of Tokyo Hospital, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan.Cartilage repair necessitates regenerative medicine because of the unreliable healing mechanism of cartilage. To yield a sufficient number of cells for transplantation, chondrocytes must be expanded in culture. However, in 2D culture, chondrocytes tend to lose their distinctive phenotypes and functionalities after serial passage, thereby limiting their efficacy for tissue engineering purposes.The mechanism of dedifferentiation in 2D culture can be attributed to various factors, including abnormal nuclear strength, stress-induced mitochondrial impairment, chromatin remodeling, ERK-1/2 and the p38/mitogen-activated protein kinase (MAPK) signaling pathway. These mechanisms collectively contribute to the loss of chondrocyte phenotype and reduced production of cartilage-specific extracellular matrix (ECM) components.Chondrocyte 3D culture methods have emerged as promising solutions to prevent dedifferentiation. Techniques, such as scaffold-based culture and scaffold-free approaches, provide chondrocytes with a more physiologically relevant environment, promoting their differentiation and matrix synthesis. These methods have been used in cartilage tissue engineering to create engineered cartilage constructs for transplantation and joint repair.However, chondrocyte 3D culture still has limitations, such as low viability and proliferation rate, and also difficulties in passage under 3D condition. These indicate challenges of obtaining a sufficient number of chondrocytes for large-scale tissue production. To address these issues, ongoing studies of many research groups have been focusing on refining culture conditions, optimizing scaffold materials, and exploring novel cell sources such as stem cells to enhance the quality and quantity of engineered cartilage tissues.Although obstacles remain, continuous endeavors to enhance culture techniques and overcome limitations offer a promising outlook for the advancement of more efficient strategies for cartilage regeneration.http://www.sciencedirect.com/science/article/pii/S2319417024000891
spellingShingle Yu-Ying Chu
Atsuhiko Hikita
Yukiyo Asawa
Kazuto Hoshi
Advancements in chondrocyte 3-dimensional embedded culture: Implications for tissue engineering and regenerative medicine
Biomedical Journal
title Advancements in chondrocyte 3-dimensional embedded culture: Implications for tissue engineering and regenerative medicine
title_full Advancements in chondrocyte 3-dimensional embedded culture: Implications for tissue engineering and regenerative medicine
title_fullStr Advancements in chondrocyte 3-dimensional embedded culture: Implications for tissue engineering and regenerative medicine
title_full_unstemmed Advancements in chondrocyte 3-dimensional embedded culture: Implications for tissue engineering and regenerative medicine
title_short Advancements in chondrocyte 3-dimensional embedded culture: Implications for tissue engineering and regenerative medicine
title_sort advancements in chondrocyte 3 dimensional embedded culture implications for tissue engineering and regenerative medicine
url http://www.sciencedirect.com/science/article/pii/S2319417024000891
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AT yukiyoasawa advancementsinchondrocyte3dimensionalembeddedcultureimplicationsfortissueengineeringandregenerativemedicine
AT kazutohoshi advancementsinchondrocyte3dimensionalembeddedcultureimplicationsfortissueengineeringandregenerativemedicine