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负载镁基纳米花的控释水凝胶在肌腱-骨愈合中协同免疫调节和软骨再生。

Controlled-release hydrogel loaded with magnesium-based nanoflowers synergize immunomodulation and cartilage regeneration in tendon-bone healing.

作者信息

Li Jintao, Ke Haolin, Lei Xiangcheng, Zhang Jiexin, Wen Zhicheng, Xiao Zhisheng, Chen Huabin, Yao Juncheng, Wang Xuan, Wei Zhengnong, Zhang Hongrui, Pan Weilun, Shao Yan, Zhao Yitao, Xie Denghui, Zeng Chun

机构信息

Department of Sports Medicine, Center for Orthopedic Surgery, Orthopedic Hospital of Guangdong Province, The Third School of Clinical Medicine, Southern Medical University, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China.

Department of Orthopedics, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China.

出版信息

Bioact Mater. 2024 Feb 28;36:62-82. doi: 10.1016/j.bioactmat.2024.02.024. eCollection 2024 Jun.


DOI:10.1016/j.bioactmat.2024.02.024
PMID:38440323
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10909705/
Abstract

Tendon-bone interface injuries pose a significant challenge in tissue regeneration, necessitating innovative approaches. Hydrogels with integrated supportive features and controlled release of therapeutic agents have emerged as promising candidates for the treatment of such injuries. In this study, we aimed to develop a temperature-sensitive composite hydrogel capable of providing sustained release of magnesium ions (Mg). We synthesized magnesium-Procyanidin coordinated metal polyphenol nanoparticles (Mg-PC) through a self-assembly process and integrated them into a two-component hydrogel. The hydrogel was composed of dopamine-modified hyaluronic acid (Dop-HA) and F127. To ensure controlled release and mitigate the "burst release" effect of Mg, we covalently crosslinked the Mg-PC nanoparticles through coordination bonds with the catechol moiety within the hydrogel. This crosslinking strategy extended the release window of Mg concentrations for up to 56 days. The resulting hydrogel (Mg-PC@Dop-HA/F127) exhibited favorable properties, including injectability, thermosensitivity and shape adaptability, making it suitable for injection and adaptation to irregularly shaped supraspinatus implantation sites. Furthermore, the hydrogel sustained the release of Mg and Procyanidins, which attracted mesenchymal stem and progenitor cells, alleviated inflammation, and promoted macrophage polarization towards the M2 phenotype. Additionally, it enhanced collagen synthesis and mineralization, facilitating the repair of the tendon-bone interface. By incorporating multilevel metal phenolic networks (MPN) to control ion release, these hybridized hydrogels can be customized for various biomedical applications.

摘要

肌腱-骨界面损伤在组织再生中构成重大挑战,需要创新方法。具有综合支持特性和治疗剂控释功能的水凝胶已成为治疗此类损伤的有前景的候选材料。在本研究中,我们旨在开发一种能够持续释放镁离子(Mg)的温度敏感复合水凝胶。我们通过自组装过程合成了镁-原花青素配位金属多酚纳米颗粒(Mg-PC),并将其整合到一种双组分水凝胶中。该水凝胶由多巴胺修饰的透明质酸(Dop-HA)和F127组成。为确保Mg的控释并减轻其“突释”效应,我们通过与水凝胶内的儿茶酚部分形成配位键将Mg-PC纳米颗粒共价交联。这种交联策略将Mg浓度的释放窗口延长至56天。所得水凝胶(Mg-PC@Dop-HA/F127)表现出良好的性能,包括可注射性、热敏性和形状适应性,使其适用于注射并适应不规则形状的冈上肌植入部位。此外,该水凝胶持续释放Mg和原花青素,吸引间充质干/祖细胞,减轻炎症,并促进巨噬细胞向M2表型极化。此外,它增强了胶原蛋白合成和矿化,促进了肌腱-骨界面的修复。通过纳入多级金属酚网络(MPN)来控制离子释放,这些杂化水凝胶可针对各种生物医学应用进行定制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b699/10909705/7d5b1807c54f/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b699/10909705/bbd9ecb96bef/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b699/10909705/f0311d6b9dd6/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b699/10909705/2406dc103757/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b699/10909705/2f7d8e64bc2e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b699/10909705/7d5b1807c54f/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b699/10909705/bbd9ecb96bef/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b699/10909705/f0311d6b9dd6/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b699/10909705/2406dc103757/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b699/10909705/2f7d8e64bc2e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b699/10909705/7d5b1807c54f/gr6.jpg

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[3]
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[4]
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[5]
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[7]
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[8]
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[9]
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本文引用的文献

[1]
Progress in Pluronic F127 Derivatives for Application in Wound Healing and Repair.

Int J Nanomedicine. 2023

[2]
Recent advances in GelMA hydrogel transplantation for musculoskeletal disorders and related disease treatment.

Theranostics. 2023

[3]
Zinc-Based Tannin-Modified Composite Microparticulate Scaffolds with Balanced Antimicrobial Activity and Osteogenesis for Infected Bone Defect Repair.

Adv Healthc Mater. 2023-8

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Strategies for promoting tendon-bone healing: Current status and prospects.

Front Bioeng Biotechnol. 2023-1-27

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J Nanobiotechnology. 2023-1-16

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Bioactive glass-elicited stem cell-derived extracellular vesicles regulate M2 macrophage polarization and angiogenesis to improve tendon regeneration and functional recovery.

Biomaterials. 2023-3

[8]
Biosynthesized Bandages Carrying Magnesium Oxide Nanoparticles Induce Cortical Bone Formation by Modulating Endogenous Periosteal Cells.

ACS Nano. 2022-11-22

[9]
Injectable electrospun fiber-hydrogel composite sequentially releasing clonidine and ropivacaine for prolonged and walking regional analgesia.

Theranostics. 2022

[10]
Reactive Oxygen Species Scavenging Functional Hydrogel Delivers Procyanidins for the Treatment of Traumatic Brain Injury in Mice.

ACS Appl Mater Interfaces. 2022-7-14

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