Inverted colloidal crystal (ICC) hydrogel scaffolds have emerged as a new class of three-dimensional cell culture matrix that represents a unique opportunity to reproduce lymphoid tissue microenvironments. ICC geometry promotes the formation of stromal cell networks and their interaction with hematopoietic cells, a core cellular process in lymphoid tissues. When subdermally implanted, ICC hydrogel scaffolds direct unique foreign body responses to form a vascularized stromal tissue with prolonged attraction of hematopoietic cells, which together resemble lymphoid tissue microenvironments. While conceptually simple, fabrication of ICC hydrogel scaffold requires multiple steps and laborious handling of delicate materials. Here, we introduce a facile route for ICC hydrogel scaffold fabrication using expanded polystyrene (EPS) beads. EPS beads shrink and fuse in a tunable manner under pressurized thermal conditions, which serves as colloidal crystal templates for ICC scaffold fabrication. Inclusion of collagen in the precursor solution greatly simplified preparation of bioactive hydrogel scaffolds. The resultant EPS-templated bioactive ICC hydrogel scaffolds demonstrate characteristic features required for lymphoid tissue modeling in both in vitro and in vivo settings. We envision that the presented method will facilitate widespread implementation of ICC hydrogel scaffolds for lymphoid tissue engineering and other emerging applications. Impact statement Inverted colloidal crystal (ICC) hydrogel scaffolds have emerged as a new class of three-dimensional cell culture matrix that represents a unique opportunity for lymphoid tissue modeling and other emerging novel bioengineering applications. While conceptually simple, fabrication of the ICC hydrogel scaffold requires multiple steps and laborious handling of delicate materials with highly toxic chemicals. The presented method for ICC hydrogel scaffold fabrication using expanded polystyrene (EPS) beads is simple, cost-effective, and involves less toxic chemicals than conventional methods, while retaining comparable biological significance. We envision that EPS bead-based hydrogel scaffold fabrication will greatly facilitate the widespread implementation of ICC hydrogel scaffolds and their practical applications.

中文翻译：

---

使用膨胀聚苯乙烯珠制造生物活性倒置胶体晶体支架。


倒置胶体晶体（ICC）水凝胶支架已成为一种新型三维细胞培养基质，代表了复制淋巴组织微环境的独特机会。 ICC 几何形状促进基质细胞网络的形成及其与造血细胞的相互作用，造血细胞是淋巴组织中的核心细胞过程。当皮下植入时，ICC水凝胶支架会引导独特的异物反应，形成血管化的基质组织，并长期吸引造血细胞，它们一起类似于淋巴组织微环境。虽然概念上很简单，但 ICC 水凝胶支架的制造需要多个步骤，并且需要费力地处理精致的材料。在这里，我们介绍了一种使用发泡聚苯乙烯 (EPS) 珠制造 ICC 水凝胶支架的简便途径。 EPS 珠在加压热条件下以可调节的方式收缩和融合，作为 ICC 支架制造的胶体晶体模板。在前体溶液中加入胶原蛋白大大简化了生物活性水凝胶支架的制备。由此产生的 EPS 模板生物活性 ICC 水凝胶支架展示了体外和体内淋巴组织建模所需的特征。我们预计所提出的方法将促进 ICC 水凝胶支架在淋巴组织工程和其他新兴应用中的广泛应用。影响陈述倒置胶体晶体（ICC）水凝胶支架已成为一种新型三维细胞培养基质，为淋巴组织建模和其他新兴的新型生物工程应用提供了独特的机会。 虽然概念上很简单，但 ICC 水凝胶支架的制造需要多个步骤，并且需要费力地处理含有剧毒化学品的精致材料。所提出的使用发泡聚苯乙烯（EPS）珠制造ICC水凝胶支架的方法简单、经济高效，并且比传统方法涉及的有毒化学物质更少，同时保留了相当的生物学意义。我们预计，基于 EPS 珠的水凝胶支架的制造将极大地促进 ICC 水凝胶支架的广泛实施及其实际应用。