Therapeutic cells are usually administered as living agents, despite the risks of undesired cell migration and acquisition of unpredictable phenotypes. Additionally, most cell-based therapies rely on the administration of single cells, often associated with rapid in vivo clearance. 3D cellular materials may be useful to prolong the effect of cellular therapies and offer the possibility of creating structural volumetric constructs. Here, the manufacturing of shape-versatile fixed cell-based materials with immunomodulatory properties is reported. Living cell aggregates with different shapes (spheres and centimeter-long fibers) are fixed using a method compatible with maintenance of structural integrity, robustness, and flexibility of 3D constructs. The biological properties of living cells can be modulated before fixation, rendering an in vitro anti-inflammatory effect toward human macrophages, in line with a decreased activation of the nuclear factor kappa B (NF-κB) pathway that preponderantly correlated with the surface area of the materials. These findings are further corroborated in vivo in mouse skin wounds. Contact with fixed materials also reduces the proliferation of activated primary T lymphocytes, while promoting regulatory populations. The fixation of cellular constructs is proposed as a versatile phenotypic stabilization method that can be easily implemented to prepare immunomodulatory materials with therapeutic potential.

中文翻译：

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用于多靶点免疫调节的形状多功能固定细胞材料


尽管存在不期望的细胞迁移和获得不可预测的表型的风险，但治疗细胞通常作为活体制剂施用。此外，大多数基于细胞的疗法依赖于单细胞的施用，通常与体内快速清除相关。 3D 细胞材料可能有助于延长细胞疗法的效果，并提供创建结构体积构造的可能性。在此，报道了具有免疫调节特性的形状通用的固定细胞材料的制造。使用与维持 3D 结构的结构完整性、稳健性和灵活性兼容的方法固定不同形状（球体和厘米长纤维）的活细胞聚集体。 活细胞的生物学特性可以在固定前进行调节，从而对人巨噬细胞产生体外抗炎作用，这与核因子 kappa B (NF-κB) 通路激活的减少一致，该通路与活细胞的表面积显着相关材料。这些发现在小鼠皮肤伤口的体内得到了进一步证实。与固定材料接触还会减少活化的初级 T 淋巴细胞的增殖，同时促进调节群体的增殖。细胞结构的固定被认为是一种多功能的表型稳定方法，可以很容易地用于制备具有治疗潜力的免疫调节材料。