Biphasic biomimetic scaffolds based on a regionally decalcified bone framework and pre-chondrogenic microspheres for osteochondral defect repair

Osteochondral defects are still facing a significant challenge in clinical surgery, making post-trauma repair difficult. Tissue engineering has provided a promising approach to solving these defects. However, existing scaffolds cannot replicate the complex biphasic cartilage-bone microenvironment wi...

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Main Authors: Zhuo Liang, Qingqing Pan, Fei Xue, Jingdi Zhang, Zhenlin Fan, Weiyun Wang, Xueqiang Guo, Zhuang Qian, Yaping Shen, Wenjuan Song, Lei Wang, Guangdong Zhou, Yong He, Wenjie Ren
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Language:English
Published: Elsevier 2025-04-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425000523
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author Zhuo Liang
Qingqing Pan
Fei Xue
Jingdi Zhang
Zhenlin Fan
Weiyun Wang
Xueqiang Guo
Zhuang Qian
Yaping Shen
Wenjuan Song
Lei Wang
Guangdong Zhou
Yong He
Wenjie Ren
author_facet Zhuo Liang
Qingqing Pan
Fei Xue
Jingdi Zhang
Zhenlin Fan
Weiyun Wang
Xueqiang Guo
Zhuang Qian
Yaping Shen
Wenjuan Song
Lei Wang
Guangdong Zhou
Yong He
Wenjie Ren
author_sort Zhuo Liang
collection DOAJ
description Osteochondral defects are still facing a significant challenge in clinical surgery, making post-trauma repair difficult. Tissue engineering has provided a promising approach to solving these defects. However, existing scaffolds cannot replicate the complex biphasic cartilage-bone microenvironment with accuracy. We aimed to develop a biphasic biomimetic scaffold with regionally regulated vascularization that promoted chondrogenesis and osteogenesis through bidirectional regulation of endochondral ossification. This scaffold consisted of pre-chondrogenic microspheres (PCMs) and a decalcified bone frame prepared by decalcifying the cartilage layer and bone layer of the scaffold to varying degrees. Incorporation of PCMs into the cartilage layer created a microenvironment that promoted cartilage regeneration while axitinib was modified to inhibit vascularization and enhance cartilage regeneration. The bone layer provided a microenvironment that promoted endochondral ossification and facilitated bone repair. In vitro studies have shown that axitinib-modified cartilage layers significantly inhibit the VEGF expression of pre-chondrogenic cells, while decalcified bone powder from the bone layer significantly promotes the ossification of PCMs. In vivo experiments indicated that this decalcified bone frame controls the endochondral ossification of PCMs through regionalized angiogenesis, promoting the integrated regeneration and reconstruction of osteochondral defects in rabbit knee joints. These results suggest that our designed demineralized bone frame can precisely engineer the osteochondral regeneration microenvironment, providing theoretical guidance for the integrated regeneration and repair of anisotropic tissue injuries.
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spelling doaj-art-f401b843a4d246a2aad7e0e2e20e73112025-01-16T04:29:11ZengElsevierMaterials Today Bio2590-00642025-04-0131101494Biphasic biomimetic scaffolds based on a regionally decalcified bone framework and pre-chondrogenic microspheres for osteochondral defect repairZhuo Liang0Qingqing Pan1Fei Xue2Jingdi Zhang3Zhenlin Fan4Weiyun Wang5Xueqiang Guo6Zhuang Qian7Yaping Shen8Wenjuan Song9Lei Wang10Guangdong Zhou11Yong He12Wenjie Ren13Clinical Medical Center of Tissue Engineering and Regeneration, The First Affiliated Hospital of Xinxiang Medical University, The Third Affiliated Hospital of Xinxiang Medical University, Institutes of Health Central Plain, Xinxiang Medical University, Xinxiang, 453003, ChinaClinical Medical Center of Tissue Engineering and Regeneration, The First Affiliated Hospital of Xinxiang Medical University, The Third Affiliated Hospital of Xinxiang Medical University, Institutes of Health Central Plain, Xinxiang Medical University, Xinxiang, 453003, ChinaClinical Medical Center of Tissue Engineering and Regeneration, The First Affiliated Hospital of Xinxiang Medical University, The Third Affiliated Hospital of Xinxiang Medical University, Institutes of Health Central Plain, Xinxiang Medical University, Xinxiang, 453003, ChinaClinical Medical Center of Tissue Engineering and Regeneration, The First Affiliated Hospital of Xinxiang Medical University, The Third Affiliated Hospital of Xinxiang Medical University, Institutes of Health Central Plain, Xinxiang Medical University, Xinxiang, 453003, ChinaClinical Medical Center of Tissue Engineering and Regeneration, The First Affiliated Hospital of Xinxiang Medical University, The Third Affiliated Hospital of Xinxiang Medical University, Institutes of Health Central Plain, Xinxiang Medical University, Xinxiang, 453003, ChinaClinical Medical Center of Tissue Engineering and Regeneration, The First Affiliated Hospital of Xinxiang Medical University, The Third Affiliated Hospital of Xinxiang Medical University, Institutes of Health Central Plain, Xinxiang Medical University, Xinxiang, 453003, ChinaClinical Medical Center of Tissue Engineering and Regeneration, The First Affiliated Hospital of Xinxiang Medical University, The Third Affiliated Hospital of Xinxiang Medical University, Institutes of Health Central Plain, Xinxiang Medical University, Xinxiang, 453003, ChinaClinical Medical Center of Tissue Engineering and Regeneration, The First Affiliated Hospital of Xinxiang Medical University, The Third Affiliated Hospital of Xinxiang Medical University, Institutes of Health Central Plain, Xinxiang Medical University, Xinxiang, 453003, ChinaClinical Medical Center of Tissue Engineering and Regeneration, The First Affiliated Hospital of Xinxiang Medical University, The Third Affiliated Hospital of Xinxiang Medical University, Institutes of Health Central Plain, Xinxiang Medical University, Xinxiang, 453003, ChinaClinical Medical Center of Tissue Engineering and Regeneration, The First Affiliated Hospital of Xinxiang Medical University, The Third Affiliated Hospital of Xinxiang Medical University, Institutes of Health Central Plain, Xinxiang Medical University, Xinxiang, 453003, ChinaClinical Medical Center of Tissue Engineering and Regeneration, The First Affiliated Hospital of Xinxiang Medical University, The Third Affiliated Hospital of Xinxiang Medical University, Institutes of Health Central Plain, Xinxiang Medical University, Xinxiang, 453003, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Key Laboratory of Tissue Engineering, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Corresponding author.The Second Affiliated Hospital of Zhejiang University and Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China; Corresponding author.Clinical Medical Center of Tissue Engineering and Regeneration, The First Affiliated Hospital of Xinxiang Medical University, The Third Affiliated Hospital of Xinxiang Medical University, Institutes of Health Central Plain, Xinxiang Medical University, Xinxiang, 453003, China; Corresponding author.Osteochondral defects are still facing a significant challenge in clinical surgery, making post-trauma repair difficult. Tissue engineering has provided a promising approach to solving these defects. However, existing scaffolds cannot replicate the complex biphasic cartilage-bone microenvironment with accuracy. We aimed to develop a biphasic biomimetic scaffold with regionally regulated vascularization that promoted chondrogenesis and osteogenesis through bidirectional regulation of endochondral ossification. This scaffold consisted of pre-chondrogenic microspheres (PCMs) and a decalcified bone frame prepared by decalcifying the cartilage layer and bone layer of the scaffold to varying degrees. Incorporation of PCMs into the cartilage layer created a microenvironment that promoted cartilage regeneration while axitinib was modified to inhibit vascularization and enhance cartilage regeneration. The bone layer provided a microenvironment that promoted endochondral ossification and facilitated bone repair. In vitro studies have shown that axitinib-modified cartilage layers significantly inhibit the VEGF expression of pre-chondrogenic cells, while decalcified bone powder from the bone layer significantly promotes the ossification of PCMs. In vivo experiments indicated that this decalcified bone frame controls the endochondral ossification of PCMs through regionalized angiogenesis, promoting the integrated regeneration and reconstruction of osteochondral defects in rabbit knee joints. These results suggest that our designed demineralized bone frame can precisely engineer the osteochondral regeneration microenvironment, providing theoretical guidance for the integrated regeneration and repair of anisotropic tissue injuries.http://www.sciencedirect.com/science/article/pii/S2590006425000523Biphasic biomimetic scaffoldsEndochondral ossificationOsteochondral repairPre-chondrogenic microspheresAxitinib
spellingShingle Zhuo Liang
Qingqing Pan
Fei Xue
Jingdi Zhang
Zhenlin Fan
Weiyun Wang
Xueqiang Guo
Zhuang Qian
Yaping Shen
Wenjuan Song
Lei Wang
Guangdong Zhou
Yong He
Wenjie Ren
Biphasic biomimetic scaffolds based on a regionally decalcified bone framework and pre-chondrogenic microspheres for osteochondral defect repair
Materials Today Bio
Biphasic biomimetic scaffolds
Endochondral ossification
Osteochondral repair
Pre-chondrogenic microspheres
Axitinib
title Biphasic biomimetic scaffolds based on a regionally decalcified bone framework and pre-chondrogenic microspheres for osteochondral defect repair
title_full Biphasic biomimetic scaffolds based on a regionally decalcified bone framework and pre-chondrogenic microspheres for osteochondral defect repair
title_fullStr Biphasic biomimetic scaffolds based on a regionally decalcified bone framework and pre-chondrogenic microspheres for osteochondral defect repair
title_full_unstemmed Biphasic biomimetic scaffolds based on a regionally decalcified bone framework and pre-chondrogenic microspheres for osteochondral defect repair
title_short Biphasic biomimetic scaffolds based on a regionally decalcified bone framework and pre-chondrogenic microspheres for osteochondral defect repair
title_sort biphasic biomimetic scaffolds based on a regionally decalcified bone framework and pre chondrogenic microspheres for osteochondral defect repair
topic Biphasic biomimetic scaffolds
Endochondral ossification
Osteochondral repair
Pre-chondrogenic microspheres
Axitinib
url http://www.sciencedirect.com/science/article/pii/S2590006425000523
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