用于树突状细胞原位募集和调节的生物粘附性大孔水凝胶。

IF 2.3 4区 医学 Q3 BIOPHYSICS
Cellular and molecular bioengineering Pub Date : 2023-07-03 eCollection Date: 2023-08-01 DOI:10.1007/s12195-023-00770-2
Joonsu Han, Rimsha Bhatta, Hua Wang
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引用次数: 0

摘要

简介:能够原位招募和调节免疫细胞的生物材料已显示出开发有效的癌症免疫疗法(如治疗性癌症疫苗)的巨大前景。与基于生物材料支架的癌症疫苗相关的一个挑战是开发大孔材料,该大孔材料具有生物相容性和稳定性,能够控制趋化因子的释放以积极招募大量树突状细胞(DC),方法:合成生物粘附性大孔明胶水凝胶,并对其力学性能、多孔结构和对组织的粘附性进行表征。分析了包括DC在内的免疫细胞对载有趋化因子的生物粘附大孔凝胶的募集。还分析了载有粒细胞-巨噬细胞集落刺激因子(GM-CSF)和肿瘤细胞外小泡(EVs)的凝胶引发肿瘤特异性CD8+T细胞反应的能力。结果:在这里,我们开发了一种生物粘附性大孔水凝胶,它可以牢固地粘附在组织上,含有足够大的大孔,可以容纳免疫细胞,具有机械韧性,并能够控制趋化因子的释放,原位募集和调节免疫细胞。大孔水凝胶由明胶和聚丙烯酸的双重交联网络组成,通过冷冻聚合引入大孔。通过将GM-CSF和肿瘤EVs结合到大孔水凝胶中,可以原位募集大量的DC来处理和呈递EV包裹的抗原。这些肿瘤抗原呈递的DC然后可以运输到淋巴组织以启动抗原特异性CD8+T细胞。结论:这种生物粘附性大孔水凝胶系统为DC的原位募集和调节以及包括肿瘤EV疫苗在内的增强免疫疗法的开发提供了一个新的平台。我们还设想了这种材料系统在药物递送、组织再生、长期免疫抑制和许多其他应用方面的前景。补充信息:在线版本包含补充材料,请访问10.1007/s12195-023-00770-2。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Bio-adhesive Macroporous Hydrogels for In Situ Recruitment and Modulation of Dendritic Cells.

Bio-adhesive Macroporous Hydrogels for In Situ Recruitment and Modulation of Dendritic Cells.

Introduction: Biomaterials that enable in situ recruitment and modulation of immune cells have demonstrated tremendous promise for developing potent cancer immunotherapy such as therapeutic cancer vaccine. One challenge related to biomaterial scaffold-based cancer vaccines is the development of macroporous materials that are biocompatible and stable, enable controlled release of chemokines to actively recruit a large number of dendritic cells (DCs), contain macropores that are large enough to home the recruited DCs, and support the survival and proliferation of DCs.

Methods: Bio-adhesive macroporous gelatin hydrogels were synthesized and characterized for mechanical properties, porous structure, and adhesion towards tissues. The recruitment of immune cells including DCs to chemokine-loaded bioadhesive macroporous gels was analyzed. The ability of gels loaded with granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor extracellular vesicles (EVs) to elicit tumor-specific CD8+ T cell responses was also analyzed.

Results: Here we develop a bioadhesive macroporous hydrogel that can strongly adhere to tissues, contain macropores that are large enough to home immune cells, are mechanically tough, and enable controlled release of chemokines to recruit and modulate immune cells in situ. The macroporous hydrogel is composed of a double crosslinked network of gelatin and polyacrylic acid, and the macropores are introduced via cryo-polymerization. By incorporating GM-CSF and tumor EVs into the macroporous hydrogel, a high number of DCs can be recruited in situ to process and present EV-encased antigens. These tumor antigen-presenting DCs can then traffic to lymphatic tissues to prime antigen-specific CD8+ T cells.

Conclusion: This bioadhesive macroporous hydrogel system provides a new platform for in situ recruitment and modulation of DCs and the development of enhanced immunotherapies including tumor EV vaccines. We also envision the promise of this material system for drug delivery, tissue regeneration, long-term immunosuppression, and many other applications.

Supplementary information: The online version contains supplementary material available at 10.1007/s12195-023-00770-2.

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来源期刊
CiteScore
5.60
自引率
3.60%
发文量
30
审稿时长
>12 weeks
期刊介绍: The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.
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