A self-assembled bilayer polypeptide-engineered hydrogel for spatiotemporal modulation of bactericidal and anti-inflammation process in osteomyelitis treatment.
A self-assembled bilayer polypeptide-engineered hydrogel for spatiotemporal modulation of bactericidal and anti-inflammation process in osteomyelitis treatment.
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DOI：
10.1186/s12951-022-01614-3
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发表时间：
2022-09-15
影响因子：
10.2
通讯作者：
Liu, Bo
中科院分区：
文献类型：
--
作者：
Xie, Xiaoting;Wei, Jiemao;Zhang, Bin;Xiong, Wei;He, Zhiyi;Zhang, Yayun;Gao, Chenghao;Zhao, Yuandi;Liu, Bo
关键词：
病原菌的耐药性和免疫抑制是骨髓炎临床停滞的主要原因。骨髓炎的理想治疗策略是通过免疫微环境的时空调节实现有效的抗菌和骨愈合。本研究以基因工程多肽AC10A和AC10ARGD为基质，通过自组装制备了双层水凝胶。将Ag2S QD@DSPE-mPEG2000-Ce6/适体（AD-Ce6/Apt）装载在顶层AC10A水凝胶（AA）中用于抗菌，并且将骨髓来源的间充质干细胞（BMSC）装载在下层AC10ARGD水凝胶（MAR）中用于骨愈合。AD-Ce6/Apt可以从AA水凝胶释放到靶S。在细菌生物膜形成之前对金黄色葡萄球菌进行杀菌，并且在用660nm激光照射下实现显著的杀菌效果。此外，AD-Ce6/Apt可诱导巨噬细胞M1型极化，从而激活免疫系统，清除残留细菌。随后，从MAR水凝胶中释放的BMSCs可以分化为成骨细胞，并通过调节巨噬细胞的M2型极化促进抗炎微环境的形成。双层AA-MAR水凝胶具有良好的生物相容性。体内外实验结果表明，AA-MAR水凝胶不仅实现了对沙门氏菌的高效光动力治疗，而且具有良好的生物活性。金黄色葡萄球菌感染，而且还促进了免疫微环境的转化，以满足每个阶段的不同需求，最终改善了术后骨再生和力学性能。这项工作提出了一种在骨髓炎治疗中时空调节免疫微环境的方法。在线版本包含补充材料，可通过10.1186/s12951 - 022 - 01614 - 3获得。
Drug resistance of pathogens and immunosuppression are the main causes of clinical stagnation of osteomyelitis. The ideal treatment strategy for osteomyelitis is to achieve both efficient antibacterial and bone healing through spatiotemporal modulation of immune microenvironment. In this study, a bilayer hydrogel based on genetically engineered polypeptide AC10A and AC10ARGD was prepared by self-assembly. Ag2S QDs@DSPE-mPEG2000-Ce6/Aptamer (AD-Ce6/Apt) was loaded in the top layer AC10A hydrogel (AA) for antibacterial, and bone marrow-derived mesenchymal stem cells (BMSCs) were loaded in the lower layer AC10ARGD hydrogel (MAR) for bone healing. The AD-Ce6/Apt can be released from the AA hydrogel to target S. aureus before bacterial biofilm formation and achieved significant bactericidal effect under irradiation with a 660 nm laser. Moreover, AD-Ce6/Apt can induce M1 type polarization of macrophages to activate the immune system and eliminate residual bacteria. Subsequently, BMSCs released from the MAR hydrogel can differentiate into osteoblasts and promote the formation of an anti-inflammatory microenvironment by regulating the M2 type polarization of macrophages. The bilayer AA-MAR hydrogel possessed good biocompatibility. The in vitro and in vivo results showed that the AA-MAR hydrogel not only realized efficient photodynamic therapy of S. aureus infection, but also promoted the transformation of immune microenvironment to fulfill the different needs of each stage, which ultimately improved bone regeneration and mechanical properties post-surgery. This work presents an approach for spatiotemporal modulation of immune microenvironment in the treatment of osteomyelitis. The online version contains supplementary material available at 10.1186/s12951-022-01614-3.
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