Rovers Maritza M, Vrehen Annika F, Dankers Patricia Y W
Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, Eindhoven, 5600, MB, the Netherlands.
Department of Biomedical Engineering, Laboratory of Chemical Biology, Eindhoven University of Technology, P.O. Box 513, Eindhoven, 5600, MB, the Netherlands.
Mater Today Bio. 2025 Aug 16;34:102214. doi: 10.1016/j.mtbio.2025.102214. eCollection 2025 Oct.
Compared to bulk hydrogels, microgels offer distinct advantages for biomedical applications. Their increased modularity and heterogeneity compared to hydrogels, combined with their small size and reversible dynamic bonding, enhance their suitability for minimally invasive cell delivery. Additionally, microgels offer greater control over porosity, resulting in the formation of intricate porous microstructures. In this work, keratocytes encapsulated in ureidopyrimidinone (UPy) supramolecular microgels functionalized with UPy-cRGD were fabricated to generate a micro stromal tissue in vitro. Both the human corneal keratocyte cell line (HCK) and primary keratocytes (PK) demonstrated effective cell-cell and cell-matrix mediated microgel assembly, resulting in the formation of self-generated scaffolds. The void spaces between the assembled microgels facilitate migration and infiltration of the cells through the biohybrid stromal tissue construct. The retention time of the cells within the microgels can be controlled by altering the microgel composition. Immunohistochemical analyses of PKs assembled tissues demonstrated the formation of stromal micro tissues, cellular extracellular matrix deposition and substantial upregulation of nuclear yes-associated-protein (YAP) during culture. This work highlights a novel supramolecular approach with promising potential for minimally invasive therapies aimed at treating corneal defects in clinical settings.
与块状水凝胶相比，微凝胶在生物医学应用中具有明显优势。与水凝胶相比，它们增加的模块化和异质性，再加上其小尺寸和可逆的动态键合，增强了它们在微创细胞递送方面的适用性。此外，微凝胶对孔隙率有更好的控制，从而导致形成复杂的多孔微结构。在这项工作中，制备了封装在经UPy-cRGD功能化的脲嘧啶酮（UPy）超分子微凝胶中的角膜细胞，以在体外生成微基质组织。人角膜细胞系（HCK）和原代角膜细胞（PK）均表现出有效的细胞-细胞和细胞-基质介导的微凝胶组装，从而形成了自发生成的支架。组装后的微凝胶之间的空隙促进了细胞通过生物杂交基质组织构建体的迁移和浸润。可以通过改变微凝胶组成来控制细胞在微凝胶中的保留时间。对PK组装组织的免疫组织化学分析表明，在培养过程中形成了基质微组织、细胞外基质沉积以及核Yes相关蛋白（YAP）的大量上调。这项工作突出了一种新颖的超分子方法，在临床环境中针对治疗角膜缺陷的微创治疗具有广阔的应用前景。
