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具有多重响应特性的透明质酸基水凝胶微球用于感染性颅骨缺损的抗菌治疗和骨再生

Hyaluronic acid-based hydrogel microspheres with multi-responsive properties for antibacterial therapy and bone regeneration in -infected skull defects.

作者信息

Lin Xiaolong, Deng Shuli, Fu Tao, Lei Yuqing, Wang Ying, Yao Jiapei, Lu Yaojun, Huang Yong, Shang Jingjing, Chen Jingjing, Zhou Xindie

机构信息

Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China.

Department of Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, School of Stomatology and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Hangzhou, Zhejiang, 310000, China.

出版信息

Mater Today Bio. 2025 Mar 26;32:101676. doi: 10.1016/j.mtbio.2025.101676. eCollection 2025 Jun.

DOI:10.1016/j.mtbio.2025.101676
PMID:40236808
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11997343/
Abstract

This study introduces hyaluronic acid-based (HA) hydrogel microspheres loaded with zinc oxide nanoparticles (ZnO-NPs) for the treatment of infectious bone defects. The microspheres were fabricated using a 3D-printing process, with a formulation consisting of 6 wt% HAD (methacrylated HA), 3 wt% AOHA (AMP-conjugated oxidized HA), 1 % BOHA (phenylboric acid-conjugated HA), 0.5 % photoinitiator, and 0.05 % ZnO-NPs. , the hydrogel microspheres demonstrated significant antibacterial activity against , with colony counts and biofilm inhibition assays showing a marked reduction in bacterial growth after 12 and 24 h. The release of antimicrobial peptides (AMPs) was enhanced in acidic conditions and in the presence of hyaluronidase. The microspheres also promoted osteogenic differentiation of bone marrow stromal cells (BMSCs), as evidenced by increased expression of osteogenic markers (ALP, OCN, OPN, and COL-1). , the hydrogel microspheres were tested in a rat skull defect model, showing significant bone regeneration, improved angiogenesis, and an anti-inflammatory response. These results indicate that ABOHA@ZnO hydrogel microspheres provide a promising strategy for treating infectious bone defects by combining antimicrobial, osteogenic.

摘要

本研究介绍了负载氧化锌纳米颗粒(ZnO-NPs)的基于透明质酸(HA)的水凝胶微球用于治疗感染性骨缺损。这些微球采用3D打印工艺制备,配方包括6 wt% 的HAD(甲基丙烯酸化透明质酸)、3 wt% 的AOHA(AMP共轭氧化透明质酸)、1% 的BOHA(苯硼酸共轭透明质酸)、0.5% 的光引发剂和0.05% 的ZnO-NPs。水凝胶微球对……表现出显著的抗菌活性,菌落计数和生物膜抑制试验表明在12小时和24小时后细菌生长明显减少。在酸性条件下和存在透明质酸酶的情况下,抗菌肽(AMPs)的释放增强。微球还促进了骨髓间充质干细胞(BMSCs)的成骨分化,成骨标志物(ALP、OCN、OPN和COL-1)表达增加证明了这一点。此外,水凝胶微球在大鼠颅骨缺损模型中进行了测试,显示出显著的骨再生、改善的血管生成和抗炎反应。这些结果表明,ABOHA@ZnO水凝胶微球通过结合抗菌和成骨作用,为治疗感染性骨缺损提供了一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/e253087f4a74/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/6d2621b7becf/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/1b5cc024a31d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/cbf21b7d4b93/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/b3795c7440f6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/300ebc4662ef/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/dcd556b820fc/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/6dbc0a129966/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/1eea63e93086/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/7675fab91278/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/e253087f4a74/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/6d2621b7becf/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/1b5cc024a31d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/cbf21b7d4b93/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/b3795c7440f6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/300ebc4662ef/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/dcd556b820fc/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/6dbc0a129966/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/1eea63e93086/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/7675fab91278/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0906/11997343/e253087f4a74/gr9.jpg

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