Functional meniscus reconstruction with biological and biomechanical heterogeneities through topological self-induction of stem cells

Meniscus injury is one of the most common sports injuries within the knee joint, which is also a crucial pathogenic factor for osteoarthritis (OA). The current meniscus substitution products are far from able to restore meniscal biofunctions due to the inability to reconstruct the gradient heterogen...

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Main Authors: Mingze Du, Kangze Liu, Huinan Lai, Jin Qian, Liya Ai, Jiying Zhang, Jun Yin, Dong Jiang
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2024-06-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X24000860
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author Mingze Du
Kangze Liu
Huinan Lai
Jin Qian
Liya Ai
Jiying Zhang
Jun Yin
Dong Jiang
author_facet Mingze Du
Kangze Liu
Huinan Lai
Jin Qian
Liya Ai
Jiying Zhang
Jun Yin
Dong Jiang
author_sort Mingze Du
collection DOAJ
description Meniscus injury is one of the most common sports injuries within the knee joint, which is also a crucial pathogenic factor for osteoarthritis (OA). The current meniscus substitution products are far from able to restore meniscal biofunctions due to the inability to reconstruct the gradient heterogeneity of natural meniscus from biological and biomechanical perspectives. Here, inspired by the topology self-induced effect and native meniscus microstructure, we present an innovative tissue-engineered meniscus (TEM) with a unique gradient-sized diamond-pored microstructure (GSDP-TEM) through dual-stage temperature control 3D-printing system based on the mechanical/biocompatibility compatible high Mw poly(ε-caprolactone) (PCL). Biologically, the unique gradient microtopology allows the seeded mesenchymal stem cells with spatially heterogeneous differentiation, triggering gradient transition of the extracellular matrix (ECM) from the inside out. Biomechanically, GSDP-TEM presents excellent circumferential tensile modulus and load transmission ability similar to the natural meniscus. After implantation in rabbit knee, GSDP-TEM induces the regeneration of biomimetic heterogeneous neomeniscus and efficiently alleviates joint degeneration. This study provides an innovative strategy for functional meniscus reconstruction. Topological self-induced cell differentiation and biomechanical property also provides a simple and effective solution for other complex heterogeneous structure reconstructions in the human body and possesses high clinical translational potential.
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spelling doaj.art-11e63bb13b9b429599e48f9bccd351ed2024-03-13T04:46:14ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2024-06-0136358375Functional meniscus reconstruction with biological and biomechanical heterogeneities through topological self-induction of stem cellsMingze Du0Kangze Liu1Huinan Lai2Jin Qian3Liya Ai4Jiying Zhang5Jun Yin6Dong Jiang7Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing Key Laboratory of Sports Injuries, Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing, ChinaSchool of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 639798, SingaporeDepartment of Engineering Mechanics, Key Laboratory of Soft Machines and Smart Devices of Zhejiang Province, Zhejiang University, Zhejiang, 310058, ChinaDepartment of Engineering Mechanics, Key Laboratory of Soft Machines and Smart Devices of Zhejiang Province, Zhejiang University, Zhejiang, 310058, ChinaDepartment of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing Key Laboratory of Sports Injuries, Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing, ChinaDepartment of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing Key Laboratory of Sports Injuries, Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing, ChinaThe State Key Laboratory of Fluid Power Transmission and Control Systems, Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Zhejiang, 310058, China; Corresponding author. The State Key Laboratory of Fluid Power Transmission and Control Systems, Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Zhejiang, 310058, China.Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing Key Laboratory of Sports Injuries, Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing, China; Corresponding author. Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing Key Laboratory of Sports Injuries, Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing, China.Meniscus injury is one of the most common sports injuries within the knee joint, which is also a crucial pathogenic factor for osteoarthritis (OA). The current meniscus substitution products are far from able to restore meniscal biofunctions due to the inability to reconstruct the gradient heterogeneity of natural meniscus from biological and biomechanical perspectives. Here, inspired by the topology self-induced effect and native meniscus microstructure, we present an innovative tissue-engineered meniscus (TEM) with a unique gradient-sized diamond-pored microstructure (GSDP-TEM) through dual-stage temperature control 3D-printing system based on the mechanical/biocompatibility compatible high Mw poly(ε-caprolactone) (PCL). Biologically, the unique gradient microtopology allows the seeded mesenchymal stem cells with spatially heterogeneous differentiation, triggering gradient transition of the extracellular matrix (ECM) from the inside out. Biomechanically, GSDP-TEM presents excellent circumferential tensile modulus and load transmission ability similar to the natural meniscus. After implantation in rabbit knee, GSDP-TEM induces the regeneration of biomimetic heterogeneous neomeniscus and efficiently alleviates joint degeneration. This study provides an innovative strategy for functional meniscus reconstruction. Topological self-induced cell differentiation and biomechanical property also provides a simple and effective solution for other complex heterogeneous structure reconstructions in the human body and possesses high clinical translational potential.http://www.sciencedirect.com/science/article/pii/S2452199X24000860Tissue-engineered meniscusFunctional reconstructionMesenchymal stem cellsHeterogeneityTopology structure
spellingShingle Mingze Du
Kangze Liu
Huinan Lai
Jin Qian
Liya Ai
Jiying Zhang
Jun Yin
Dong Jiang
Functional meniscus reconstruction with biological and biomechanical heterogeneities through topological self-induction of stem cells
Bioactive Materials
Tissue-engineered meniscus
Functional reconstruction
Mesenchymal stem cells
Heterogeneity
Topology structure
title Functional meniscus reconstruction with biological and biomechanical heterogeneities through topological self-induction of stem cells
title_full Functional meniscus reconstruction with biological and biomechanical heterogeneities through topological self-induction of stem cells
title_fullStr Functional meniscus reconstruction with biological and biomechanical heterogeneities through topological self-induction of stem cells
title_full_unstemmed Functional meniscus reconstruction with biological and biomechanical heterogeneities through topological self-induction of stem cells
title_short Functional meniscus reconstruction with biological and biomechanical heterogeneities through topological self-induction of stem cells
title_sort functional meniscus reconstruction with biological and biomechanical heterogeneities through topological self induction of stem cells
topic Tissue-engineered meniscus
Functional reconstruction
Mesenchymal stem cells
Heterogeneity
Topology structure
url http://www.sciencedirect.com/science/article/pii/S2452199X24000860
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