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具有按需分布的锰/镁掺杂羟基磷灰石@FeO的连续机械梯度水凝胶用于功能性骨软骨再生。

Continuous mechanical-gradient hydrogel with on-demand distributed Mn/Mg-doped hydroxyapatite@FeO for functional osteochondral regeneration.

作者信息

Xu Junwei, Cui Yi, Li Ping, Sun Xuemei, Chen Zhiheng, Wang Jingxi, Gu Xuenan, Wang Xiaogang, Fan Yubo

机构信息

School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, China.

The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, 528300, China.

出版信息

Bioact Mater. 2025 Mar 27;49:608-626. doi: 10.1016/j.bioactmat.2025.03.013. eCollection 2025 Jul.


DOI:10.1016/j.bioactmat.2025.03.013
PMID:40212781
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11985089/
Abstract

Traditional layered gradient scaffolds are susceptible to delamination owing to abrupt stress alterations, thereby rendering them inefficacious for the integrated repair of osteochondral defects. This study proposed a novel hydrogel possessing continuous magnetic-mechanical and multiple functional metal elements gradients. The establishment of these gradients within the hydrogel was accomplished by first applying a magnetic field to FMHM particles (FeO deposited with Mg-doped hydroxyapatite (MgHA@FeO) and grafted with γ-(methacryloyloxy) propyl trimethoxysilane) dispersed in poly (ethylene glycol) diacrylate/sodium alginate solution to create a gradient, followed by thermal polymerization to achieve the magnetic and mechanical gradients. Subsequently secondary crosslinking with Mn realized the gradient distribution of Mn which was reverse to the gradient of MgHA@FeO. The on-demand gradient distributions of Mn and MgHA@FeO enhanced cartilage and osteogenic differentiation of bone marrow-derived mesenchymal stem cells, respectively. The continuous gradient hydrogel attained remarkable repair effects on full-thickness osteochondral defects in rat knee joints. Its capacity to foster the growth of both cartilage and subchondral bone may be associated with the fact that the mechanical gradient modulated the gradient nuclear localization and expression of the mechanosensitive factor Yes-associated protein 1. With stiffness and magnetism gradients, along with the on-demand synergistic impacts of multi-gradient metal elements Mn-Fe/Mg/Ca, this hydrogel presents a prospective option for the regeneration of tissues/interface tissues exhibiting physiological gradients.

摘要

传统的分层梯度支架由于应力突变容易发生分层,因此在骨软骨缺损的综合修复中效果不佳。本研究提出了一种具有连续磁机械和多功能金属元素梯度的新型水凝胶。通过首先对分散在聚(乙二醇)二丙烯酸酯/海藻酸钠溶液中的FMHM颗粒(沉积有镁掺杂羟基磷灰石(MgHA@FeO)并接枝有γ-(甲基丙烯酰氧基)丙基三甲氧基硅烷的FeO)施加磁场以形成梯度,随后进行热聚合以实现磁和机械梯度,从而在水凝胶中建立这些梯度。随后与Mn进行二次交联实现了Mn的梯度分布,该分布与MgHA@FeO的梯度相反。Mn和MgHA@FeO的按需梯度分布分别增强了骨髓间充质干细胞的软骨和成骨分化。这种连续梯度水凝胶对大鼠膝关节全层骨软骨缺损取得了显著的修复效果。其促进软骨和软骨下骨生长的能力可能与机械梯度调节机械敏感因子Yes相关蛋白1的梯度核定位和表达这一事实有关。凭借刚度和磁性梯度,以及多梯度金属元素Mn-Fe/Mg/Ca的按需协同作用,这种水凝胶为具有生理梯度的组织/界面组织的再生提供了一种有前景的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976a/11985089/b499df489b70/gr7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976a/11985089/a1c4635b3784/gr1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976a/11985089/4fa2df735f7c/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976a/11985089/a4e96e709e65/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976a/11985089/c7c875e4af63/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976a/11985089/e62b23a41288/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976a/11985089/b499df489b70/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976a/11985089/db4a956236b5/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976a/11985089/e7cd15dfffcd/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976a/11985089/a1c4635b3784/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976a/11985089/be2c385bac88/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976a/11985089/4fa2df735f7c/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976a/11985089/a4e96e709e65/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976a/11985089/c7c875e4af63/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976a/11985089/e62b23a41288/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976a/11985089/b499df489b70/gr7.jpg

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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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