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
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DOI：
10.1007/s12195-023-00770-2
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发表时间：
2023-07-03
影响因子：
2.8
通讯作者：
Wang，Hua
中科院分区：
文献类型：
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作者：
Han，Joonsu;Bhatta，Rimsha;Wang，Hua
生物材料能够原位募集和调节免疫细胞，在开发有效的癌症免疫治疗如治疗性癌症疫苗方面具有巨大的前景。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，其是生物相容的和稳定的，能够控制释放趋化因子以主动募集大量树突状细胞（DC），含有大到足以使募集的DC归巢的大孔，方法合成生物粘附性大孔明胶水凝胶并对其机械性能进行表征，多孔结构和对组织的粘附。分析了包括DC在内的免疫细胞向负载趋化因子的生物粘附性大孔凝胶的募集。凝胶装载粒细胞-巨噬细胞集落刺激因子（GM-CSF）和肿瘤细胞外囊泡（EVs）引发肿瘤特异性CD 8 +T细胞应答的能力也进行了分析。ResultsHere我们开发了一种生物粘附性大孔水凝胶，它可以牢固地粘附于组织，含有足够大的大孔以容纳免疫细胞，机械上坚韧，并且能够控制趋化因子的释放以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，大孔通过低温聚合引入。通过将GM-CSF和肿瘤EV掺入大孔水凝胶中，可以原位募集大量DC以加工和呈递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，以引发抗原特异性的CD 8 +T cells.ConclusionThis bioadhesive macroporous hydrogel system提供了一个新的平台，用于原位募集和调节DC和开发增强的免疫疗法，包括肿瘤EV疫苗。我们还设想了这种材料系统用于药物输送、组织再生、长期免疫抑制和许多其他应用的前景。
IntroductionBiomaterials 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 DCsMethodsBio-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.ResultsHere 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.ConclusionThis 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.