Sequential simulation of regeneration-specific microenvironments using scaffolds loaded with nanoplatelet vesicles enhances bone regeneration

Bone regeneration is a complex and coordinated physiological process, and the different stages of this process have corresponding microenvironments to support cell development and physiological activities. However, biological scaffolds that provide different three-dimensional environments during dif...

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Main Authors: Wenshuai Li, Qichen Shen, Tong Tong, Hongsen Tian, Xiaowei Lian, Haoli Wang, Ke Yang, Zhanqiu Dai, Yijun Li, Xianhua Chen, Qingqing Wang, Dan Yang, Feng Wang, Feng Hao, Linfeng Wang
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Language:English
Published: KeAi Communications Co., Ltd. 2025-08-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X25001586
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author Wenshuai Li
Qichen Shen
Tong Tong
Hongsen Tian
Xiaowei Lian
Haoli Wang
Ke Yang
Zhanqiu Dai
Yijun Li
Xianhua Chen
Qingqing Wang
Dan Yang
Feng Wang
Feng Hao
Linfeng Wang
author_facet Wenshuai Li
Qichen Shen
Tong Tong
Hongsen Tian
Xiaowei Lian
Haoli Wang
Ke Yang
Zhanqiu Dai
Yijun Li
Xianhua Chen
Qingqing Wang
Dan Yang
Feng Wang
Feng Hao
Linfeng Wang
author_sort Wenshuai Li
collection DOAJ
description Bone regeneration is a complex and coordinated physiological process, and the different stages of this process have corresponding microenvironments to support cell development and physiological activities. However, biological scaffolds that provide different three-dimensional environments during different stages of bone regeneration are lacking. In this study, we report a novel composite scaffold (NPE@DCBM) inspired by the stages of bone regeneration; this scaffold was composed of a fibrin hydrogel loaded with nanoplatelet vesicles (NPVs), designated as NPE, and decellularized cancellous bone matrix (DCBM) microparticles. Initially, the NPE rapidly established a temporary microenvironment conducive to cell migration and angiogenesis. Subsequently, the DCBM simulated the molecular structure of bone and promoted new bone formation. In vitro, the NPVs regulated lipid metabolism in bone marrow mesenchymal stem cells (BMSCs), reprogramed the fate of BMSCs by activating the PI3K/AKT and MAPK/ERK positive feedback pathways, and increased BMSC functions, including proliferation, migration and proangiogenic potential. In vivo, NPV@DCBM accelerated bone tissue regeneration and repair. Initially, the NPE rapidly induced angiogenesis between DCBM microparticles, and subsequently, BMSCs differentiated into osteoblasts with DCBM microparticles at their core. In summary, the design of this composite scaffold that sequentially mimics different bone regeneration microenvironments may provide a promising strategy for bone regeneration, with clinical translational potential.
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spelling doaj-art-1796debbd2d54d00a7b38305f40555d22025-08-20T02:06:57ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-08-015047549310.1016/j.bioactmat.2025.04.018Sequential simulation of regeneration-specific microenvironments using scaffolds loaded with nanoplatelet vesicles enhances bone regenerationWenshuai Li0Qichen Shen1Tong Tong2Hongsen Tian3Xiaowei Lian4Haoli Wang5Ke Yang6Zhanqiu Dai7Yijun Li8Xianhua Chen9Qingqing Wang10Dan Yang11Feng Wang12Feng Hao13Linfeng Wang14Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China; The Key Laboratory of Orthopedic Biomechanics of Hebei Province, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China; Hangzhou OrigO Biotechnology Co. Ltd., Hangzhou, Zhejiang, 310016, ChinaHangzhou OrigO Biotechnology Co. Ltd., Hangzhou, Zhejiang, 310016, ChinaDepartment of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China; The Key Laboratory of Orthopedic Biomechanics of Hebei Province, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, ChinaDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, Zhejiang, 310016, China; Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou, Zhejiang, 310016, ChinaDepartment of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China; The Key Laboratory of Orthopedic Biomechanics of Hebei Province, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, ChinaDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, Zhejiang, 310016, China; Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou, Zhejiang, 310016, ChinaDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, Zhejiang, 310016, China; Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou, Zhejiang, 310016, ChinaDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, Zhejiang, 310016, China; Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou, Zhejiang, 310016, ChinaThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, ChinaZhejiang Institute of Medical Device Testing, Hangzhou, Zhejiang, 310016, ChinaDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, Zhejiang, 310016, China; Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Hangzhou, Zhejiang, 310016, China; Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, 315000, ChinaZhejiang DecellMatrix Biotechnology Co. Ltd., Hangzhou, Zhejiang, 310016, ChinaDepartment of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China; The Key Laboratory of Orthopedic Biomechanics of Hebei Province, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China; Corresponding author. Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China.Zhejiang DecellMatrix Biotechnology Co. Ltd., Hangzhou, Zhejiang, 310016, China; Corresponding author.Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China; The Key Laboratory of Orthopedic Biomechanics of Hebei Province, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China; Corresponding author. Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China.Bone regeneration is a complex and coordinated physiological process, and the different stages of this process have corresponding microenvironments to support cell development and physiological activities. However, biological scaffolds that provide different three-dimensional environments during different stages of bone regeneration are lacking. In this study, we report a novel composite scaffold (NPE@DCBM) inspired by the stages of bone regeneration; this scaffold was composed of a fibrin hydrogel loaded with nanoplatelet vesicles (NPVs), designated as NPE, and decellularized cancellous bone matrix (DCBM) microparticles. Initially, the NPE rapidly established a temporary microenvironment conducive to cell migration and angiogenesis. Subsequently, the DCBM simulated the molecular structure of bone and promoted new bone formation. In vitro, the NPVs regulated lipid metabolism in bone marrow mesenchymal stem cells (BMSCs), reprogramed the fate of BMSCs by activating the PI3K/AKT and MAPK/ERK positive feedback pathways, and increased BMSC functions, including proliferation, migration and proangiogenic potential. In vivo, NPV@DCBM accelerated bone tissue regeneration and repair. Initially, the NPE rapidly induced angiogenesis between DCBM microparticles, and subsequently, BMSCs differentiated into osteoblasts with DCBM microparticles at their core. In summary, the design of this composite scaffold that sequentially mimics different bone regeneration microenvironments may provide a promising strategy for bone regeneration, with clinical translational potential.http://www.sciencedirect.com/science/article/pii/S2452199X25001586Bone regenerationScaffoldsPlatelet vesiclesDecellularized cancellous bone matrixBone marrow mesenchymal stem cells
spellingShingle Wenshuai Li
Qichen Shen
Tong Tong
Hongsen Tian
Xiaowei Lian
Haoli Wang
Ke Yang
Zhanqiu Dai
Yijun Li
Xianhua Chen
Qingqing Wang
Dan Yang
Feng Wang
Feng Hao
Linfeng Wang
Sequential simulation of regeneration-specific microenvironments using scaffolds loaded with nanoplatelet vesicles enhances bone regeneration
Bioactive Materials
Bone regeneration
Scaffolds
Platelet vesicles
Decellularized cancellous bone matrix
Bone marrow mesenchymal stem cells
title Sequential simulation of regeneration-specific microenvironments using scaffolds loaded with nanoplatelet vesicles enhances bone regeneration
title_full Sequential simulation of regeneration-specific microenvironments using scaffolds loaded with nanoplatelet vesicles enhances bone regeneration
title_fullStr Sequential simulation of regeneration-specific microenvironments using scaffolds loaded with nanoplatelet vesicles enhances bone regeneration
title_full_unstemmed Sequential simulation of regeneration-specific microenvironments using scaffolds loaded with nanoplatelet vesicles enhances bone regeneration
title_short Sequential simulation of regeneration-specific microenvironments using scaffolds loaded with nanoplatelet vesicles enhances bone regeneration
title_sort sequential simulation of regeneration specific microenvironments using scaffolds loaded with nanoplatelet vesicles enhances bone regeneration
topic Bone regeneration
Scaffolds
Platelet vesicles
Decellularized cancellous bone matrix
Bone marrow mesenchymal stem cells
url http://www.sciencedirect.com/science/article/pii/S2452199X25001586
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