One-step strategy for fabricating icariin-encapsulated biomimetic Scaffold: Orchestrating immune, angiogenic, and osteogenic cascade for enhanced bone regeneration

The repair of bone defects relies on the intricate coordination of inflammation, angiogenesis, and osteogenesis. However, scaffolds capable of integrating osteo-immunomodulation and vascular-bone coupling to cascade-activate these processes remain a challenge. Here, a biomimetic scaffold (CHP@IC) wi...

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Main Authors: Fengxin Zhao, Fuying Chen, Tao Song, Luoqiang Tian, Hang Guo, Dongxiao Li, Jirong Yang, Kai Zhang, Yumei Xiao, Xingdong Zhang
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-10-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X25002294
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author Fengxin Zhao
Fuying Chen
Tao Song
Luoqiang Tian
Hang Guo
Dongxiao Li
Jirong Yang
Kai Zhang
Yumei Xiao
Xingdong Zhang
author_facet Fengxin Zhao
Fuying Chen
Tao Song
Luoqiang Tian
Hang Guo
Dongxiao Li
Jirong Yang
Kai Zhang
Yumei Xiao
Xingdong Zhang
author_sort Fengxin Zhao
collection DOAJ
description The repair of bone defects relies on the intricate coordination of inflammation, angiogenesis, and osteogenesis. However, scaffolds capable of integrating osteo-immunomodulation and vascular-bone coupling to cascade-activate these processes remain a challenge. Here, a biomimetic scaffold (CHP@IC) with in situ PLGA@icariin (PLGA@IC) microspheres encapsulation was successfully fabricated using a one-step emulsification and polymerization strategy. This approach not only simplifies the fabrication process but also ensures high encapsulation efficiency and sustained release of IC through PLGA@IC microspheres. The findings from subcutaneous implantation, network pharmacology-predicted molecular targets, and in vitro studies collectively reveal that the CHP@IC-induced M2 polarization of macrophages via STAT3 signaling pathway triggers the sequential activation of inflammation, angiogenesis, and osteogenesis to enhance bone regeneration. The CHP@IC scaffold exhibited a significant osteogenic advantage in cranial defect repair, yielding new bone volumes approximately 3-fold and 10-fold greater than those in the CHP group and blank control group, respectively. This study not only elucidates the mechanism of IC in promoting regeneration of bone but also provides a novel method for designing scaffolds aimed at the efficient repair of bone defects.
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issn 2452-199X
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spelling doaj-art-8dad8b3e93204147bdbc643a9d1535cf2025-08-24T05:13:39ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-10-015227128610.1016/j.bioactmat.2025.06.001One-step strategy for fabricating icariin-encapsulated biomimetic Scaffold: Orchestrating immune, angiogenic, and osteogenic cascade for enhanced bone regenerationFengxin Zhao0Fuying Chen1Tao Song2Luoqiang Tian3Hang Guo4Dongxiao Li5Jirong Yang6Kai Zhang7Yumei Xiao8Xingdong Zhang9National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Research Center for Material Genome Engineering, Sichuan University, Chengdu, 610065, ChinaNational Engineering Research Center for Biomaterials, College of Biomedical Engineering, Research Center for Material Genome Engineering, Sichuan University, Chengdu, 610065, ChinaNational Engineering Research Center for Biomaterials, College of Biomedical Engineering, Research Center for Material Genome Engineering, Sichuan University, Chengdu, 610065, ChinaNational Engineering Research Center for Biomaterials, College of Biomedical Engineering, Research Center for Material Genome Engineering, Sichuan University, Chengdu, 610065, ChinaNational Engineering Research Center for Biomaterials, College of Biomedical Engineering, Research Center for Material Genome Engineering, Sichuan University, Chengdu, 610065, ChinaSichuan Academy of Chinese Medicine Science, Chengdu, Sichuan, 610042, ChinaResearch Center for Human Tissue and Organs Degeneration, Institute of Biomedical and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, ChinaNational Engineering Research Center for Biomaterials, College of Biomedical Engineering, Research Center for Material Genome Engineering, Sichuan University, Chengdu, 610065, ChinaNational Engineering Research Center for Biomaterials, College of Biomedical Engineering, Research Center for Material Genome Engineering, Sichuan University, Chengdu, 610065, China; Corresponding author.National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Research Center for Material Genome Engineering, Sichuan University, Chengdu, 610065, ChinaThe repair of bone defects relies on the intricate coordination of inflammation, angiogenesis, and osteogenesis. However, scaffolds capable of integrating osteo-immunomodulation and vascular-bone coupling to cascade-activate these processes remain a challenge. Here, a biomimetic scaffold (CHP@IC) with in situ PLGA@icariin (PLGA@IC) microspheres encapsulation was successfully fabricated using a one-step emulsification and polymerization strategy. This approach not only simplifies the fabrication process but also ensures high encapsulation efficiency and sustained release of IC through PLGA@IC microspheres. The findings from subcutaneous implantation, network pharmacology-predicted molecular targets, and in vitro studies collectively reveal that the CHP@IC-induced M2 polarization of macrophages via STAT3 signaling pathway triggers the sequential activation of inflammation, angiogenesis, and osteogenesis to enhance bone regeneration. The CHP@IC scaffold exhibited a significant osteogenic advantage in cranial defect repair, yielding new bone volumes approximately 3-fold and 10-fold greater than those in the CHP group and blank control group, respectively. This study not only elucidates the mechanism of IC in promoting regeneration of bone but also provides a novel method for designing scaffolds aimed at the efficient repair of bone defects.http://www.sciencedirect.com/science/article/pii/S2452199X25002294Biomimetic scaffoldBone regenerationIcariin deliveryOne-step strategyCascade activation
spellingShingle Fengxin Zhao
Fuying Chen
Tao Song
Luoqiang Tian
Hang Guo
Dongxiao Li
Jirong Yang
Kai Zhang
Yumei Xiao
Xingdong Zhang
One-step strategy for fabricating icariin-encapsulated biomimetic Scaffold: Orchestrating immune, angiogenic, and osteogenic cascade for enhanced bone regeneration
Bioactive Materials
Biomimetic scaffold
Bone regeneration
Icariin delivery
One-step strategy
Cascade activation
title One-step strategy for fabricating icariin-encapsulated biomimetic Scaffold: Orchestrating immune, angiogenic, and osteogenic cascade for enhanced bone regeneration
title_full One-step strategy for fabricating icariin-encapsulated biomimetic Scaffold: Orchestrating immune, angiogenic, and osteogenic cascade for enhanced bone regeneration
title_fullStr One-step strategy for fabricating icariin-encapsulated biomimetic Scaffold: Orchestrating immune, angiogenic, and osteogenic cascade for enhanced bone regeneration
title_full_unstemmed One-step strategy for fabricating icariin-encapsulated biomimetic Scaffold: Orchestrating immune, angiogenic, and osteogenic cascade for enhanced bone regeneration
title_short One-step strategy for fabricating icariin-encapsulated biomimetic Scaffold: Orchestrating immune, angiogenic, and osteogenic cascade for enhanced bone regeneration
title_sort one step strategy for fabricating icariin encapsulated biomimetic scaffold orchestrating immune angiogenic and osteogenic cascade for enhanced bone regeneration
topic Biomimetic scaffold
Bone regeneration
Icariin delivery
One-step strategy
Cascade activation
url http://www.sciencedirect.com/science/article/pii/S2452199X25002294
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