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

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

Bioactive Materials (Aug 2025)

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

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

Affiliations

Wenshuai Li: 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; Hangzhou OrigO Biotechnology Co. Ltd., Hangzhou, Zhejiang, 310016, China
Qichen Shen: Hangzhou OrigO Biotechnology Co. Ltd., Hangzhou, Zhejiang, 310016, China
Tong Tong: 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
Hongsen Tian: Department 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
Xiaowei Lian: 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
Haoli Wang: Department 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
Ke Yang: Department 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
Zhanqiu Dai: Department 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
Yijun Li: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
Xianhua Chen: Zhejiang Institute of Medical Device Testing, Hangzhou, Zhejiang, 310016, China
Qingqing Wang: Department 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, China
Dan Yang: Zhejiang DecellMatrix Biotechnology Co. Ltd., Hangzhou, Zhejiang, 310016, China
Feng Wang: 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.
Feng Hao: Zhejiang DecellMatrix Biotechnology Co. Ltd., Hangzhou, Zhejiang, 310016, China; Corresponding author.
Linfeng Wang: 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.

Journal volume & issue: Vol. 50
pp. 475 – 493

Abstract

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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.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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