Nanocomposite hydrogels optimize the microenvironment by exterior/interior crosstalk for reprogramming osteoporotic homeostasis in bone defect healing

被引：1

作者：

Chen, Dengke ^{[1
,2
]}

Yang, Yuying ^{[1
,2
,5
]}

Li, Beibei ^{[1
,2
]}

Yao, Yingjuan ^{[1
,2
]}

Xu, Junyi ^{[1
,2
]}

Liu, Rongyan ^{[1
,2
]}

Peng, Jiao ^{[1
,2
]}

Chang, Zhuangpeng ^{[1
,2
]}

Zhao, Rui ^{[1
,2
]}

Hou, Ruigang ^{[1
,2
]}

Lee, Min ^{[4
]}

Xu, Xianghui ^{[3
]}

Zhang, Xiao ^{[1
,2
]}

机构：

[1] Shanxi Med Univ, Sch Pharm, Taiyuan 030001, Shanxi, Peoples R China

[2] Shanxi Med Univ, Clin Med Coll 2, Taiyuan 030001, Shanxi, Peoples R China

[3] Hunan Univ, Coll Biol, Dept Pharm, Changsha 410082, Hunan, Peoples R China

[4] Univ Calif Los Angeles, Div Oral & Syst Hlth Sci, Los Angeles, CA 90095 USA

[5] Zhejiang Univ, Sch Pharm, Hangzhou 310058, Zhejiang, Peoples R China

来源：

JOURNAL OF CONTROLLED RELEASE | 2025年 / 380卷

基金：

中国国家自然科学基金;

关键词：

Supramolecular nanocomposite hydrogels; Mild hyperthermia; Accelerated acid neutralization; Osteoclast/osteoblast balance; Osteoporotic bone regeneration; DELIVERY; PROMOTE;

D O I：

10.1016/j.jconrel.2025.02.048

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Discovering new tactics for healing bone defects becomes a worldwide challenge in osteoporosis patients. The disordered acidic microenvironment plays a pivotal role in driving the imbalance of bone homeostasis regulated by osteoblasts and osteoclasts. However, the scarcity of hydrogel materials developed to optimize local bone microenvironment has made osteoporotic defect healing more challenging. Herein, we present innovative nanocomposite hydrogels with precisely engineered microarchitectures designed to optimize the acidic micro-environment by facilitating crosstalk between exterior and interior spaces, aimed at enhancing the reconstruction of osteoporotic bone defects. The chlorogenic acid grafted chitosan as double-sided crosslinkers is specially designed to not only combine with acid-reversible Laponite (R) nanosheet via interfacial interactions but also integrate with gold nanorod (a typical photothermal agent) through catechol-Au bond. The supramolecular construction of nanocomposite hydrogels holds promise for achieving a highly continuous and homogeneous pore network microarchitecture. As expected, hydrogels display outstanding spatiotemporal local mild hyperthermia, which accelerates the neutralization reaction between OH- ions released from Laponite (R) and hydrogen ions (pH similar to 4.0). The optimized microenvironment restores osteoclast/osteoblast homeostasis, resulting in the promotion of osteoblastogenesis and inhibition of osteoclastogenesis, thereby facilitating the healing of osteoporotic bone defects. This work is hoped to design versatile hydrogels for optimizing the microenvironment, displaying promising integrative substitute materials for clinically effective treatment of osteoporotic bone defects.

引用

页码：976 / 993

页数：18

共 68 条

[21]

Lavrador P., Gaspar V.M., Mano J.F., Stimuli-responsive nanocarriers for delivery of bone therapeutics - barriers and progresses, J. Control. Release, 273, pp. 51-67, (2018)

[22]

Fu H., Wang L., Bao Q., Ni D., Hu P., Shi J., Acid neutralization and immune regulation by calcium-aluminum-layered double hydroxide for osteoporosis reversion, J. Am. Chem. Soc., 144, 20, pp. 8987-8999, (2022)

[23]

Lin X., Wang Q., Gu C., Li M., Chen K., Chen P., Tang Z., Liu X., Pan H., Liu Z., Tang R., Fan S., Smart nanosacrificial layer on the bone surface prevents osteoporosis through acid-base neutralization regulated biocascade effects, J. Am. Chem. Soc., 142, 41, pp. 17543-17556, (2020)

[24]

Lin W., Hu S., Li K., Shi Y., Pan C., Xu Z., Li D., Wang H., Li B., Chen H., Breaking osteoclast-acid vicious cycle to rescue osteoporosis via an acid responsive organic framework-based neutralizing and gene editing platform, Small, 20, 22, (2024)

[25]

Liu X., Li F., Dong Z., Gu C., Mao D., Chen J., Luo L., Huang Y., Xiao J., Li Z., Liu Z., Yang Y., Metal-polyDNA nanoparticles reconstruct osteoporotic microenvironment for enhanced osteoporosis treatment, Sci. Adv., 9, 31, (2023)

[26]

Zhou Y., Deng Y., Liu Z., Yin M., Hou M., Zhao Z., Zhou X., Yin L., Cytokine-scavenging nanodecoys reconstruct osteoclast/osteoblast balance toward the treatment of postmenopausal osteoporosis, Sci. Adv., 7, 48, (2021)

[27]

Zheng L., Zhou D., Ju F., Liu Z., Yan C., Dong Z., Chen S., Deng L., Chan S., Deng J., Zhang X., Oscillating fluid flow activated osteocyte lysate-based hydrogel for regulating osteoblast/osteoclast homeostasis to enhance bone repair, Adv. Sci., 10, 15, (2023)

[28]

Kim J., Kim B.Y., Lee J.S., Jeong Y.M., Cho H.J., Park E., Kim D., Kim S.S., Kim B.T., Choi Y.J., Won Y.Y., Jin H.S., Chung Y.S., Jeong S.Y., UBAP2 plays a role in bone homeostasis through the regulation of osteoblastogenesis and osteoclastogenesis, Nat. Commun., 14, 1, (2023)

[29]

Li Z., Wang H., Zhang K., Yang B., Xie X., Yang Z., Kong L., Shi P., Zhang Y., Ho Y.P., Zhang Z.Y., Li G., Bian L., Bisphosphonate-based hydrogel mediates biomimetic negative feedback regulation of osteoclastic activity to promote bone regeneration, Bioact. Mater., 13, pp. 9-22, (2022)

[30]

Feng Y., Ning X., Wang J., Wen Z., Cao F., You Q., Zou J., Zhou X., Sun T., Cao J., Chen X., Mace-like plasmonic Au-Pd heterostructures boost near-infrared photoimmunotherapy, Adv. Sci., 10, 6, (2023)

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