The marriage of immunomodulatory,angiogenic,and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scafold for military medicine

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外文摘要：Background:Most bone-related injuries to grassroots troops are caused by training or accidental injuries.To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops,it is imperative to develop new strategies and scafolds to promote bone regeneration.Methods:In this study,a porous piezoelectric hydrogel bone scafold was fabricated by incorporating polydopamine(PDA)-modified ceramic hydroxyapatite(PDA-hydroxyapatite,PHA)and PDA-modified barium titanate(PDA-BaTiO3,PBT)nanoparticles into a chitosan/gelatin(Cs/Gel)matrix.The physical and chemical properties of the Cs/Gel/PHA scafold with 0-10 wt%PBT were analyzed.Cell and animal experiments were performed to characterize the immunomodulatory,angiogenic,and osteogenic capabilities of the piezoelectric hydrogel scafold in vitro and in vivo.Results:The incorporation of BaTiO3 into the scafold improved its mechanical properties and increased self-generated electricity.Due to their endogenous piezoelectric stimulation and bioactive constituents,the prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory,angiogenic,and osteogenic capabilities;they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration,tube formation,and angiogenic differentiation of human umbilical vein endothelial cells(HUVECs)and facilitated the migration,osteo-differentiation,and extracellular matrix(ECM)mineralization of MC3T3-E1 cells.The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model.The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis,and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization.Conclusions:The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation,angiogenesis,and osteogenesis functions may be used as a substitute in periosteum injuries,thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat efectiveness in grassroots troops.

外文关键词：

Piezoelectric hydrogelTissue engineering scafoldImmunomodulationAngiogenesisOsteogenic differentiation

作者：

Ping Wu、Lin Shen、Hui-Fan Liu、Xiang-Hui Zou、Juan Zhao、Yu Huang、Yu-Fan Zhu、Zhao-Yu Li、Chao Xu、Li-Hua Luo、Zhi-Qiang Luo、Min-Hao Wu、Lin Cai、Xiao-Kun Li、Zhou-Guang Wang

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作者单位：

Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research,the Fifth Affiliated Hospital of Wenzhou Medical University,Lishui 323000,Zhejiang,China

Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine,Vision and Brain Health),School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou 325000,Zhejiang,China

Department of Spine Surgery and Musculoskeletal Tumor,Zhongnan Hospital of Wuhan University,Wuhan 430071,China

National Engineering Research Center for Nanomedicine,College of Life Science and Technology,Huazhong University of Science and Technology,Wuhan 430074,China

Department of Overseas Education College,Jimei University,Xiamen 361021,Fujian,China

School and Hospital of Stomatology,Wenzhou Medical University,Wenzhou 325035,Zhejiang,China

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基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaTranslational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan UniversityChina Postdoctoral Science Foundation Funded ProjectWenzhou Medical University grant

项目编号：

8220235282271629ZNLH2022022023M732711QTJ23004

出版年：

2024

DOI：

10.1186/s40779-023-00469-5

军事医学研究(英文)

CSTPCD

ISSN：2095-7467

年,卷(期)：2024.11(3)

参考文献量70