Pamplona Regina, González-Lana Sandra, Romero Pilar, Ochoa Ignacio, Martín-Rapún Rafael, Sánchez-Somolinos Carlos
Aragón Institute of Nanoscience and Materials (INMA), Department of Organic Chemistry, CSIC-University of Zaragoza, C/ Pedro Cerbuna 12, 50009Zaragoza, Spain.
BEONCHIP S.L., CEMINEM, Campus Río Ebro. C/ Mariano Esquillor Gómez s/n, 50018Zaragoza, Spain.
ACS Appl Polym Mater. 2023 Jan 27;5(2):1487-1498. doi: 10.1021/acsapm.2c01980. eCollection 2023 Feb 10.
The mechanical microenvironment plays a crucial role in the evolution of colorectal cancer, a complex disease characterized by heterogeneous tumors with varying elasticity. Toward setting up distinct scenarios, herein, we describe the preparation and characterization of gelatin methacrylamide (GelMA)-based hydrogels two different mechanisms: free-radical photopolymerization and photo-induced thiol-ene reaction. A precise stiffness modulation of covalently crosslinked scaffolds was achieved through the application of well-defined irradiation times while keeping the intensity constant. Besides, the incorporation of thiol chemistry strongly increased stiffness with low to moderate curing times. This wide range of finely tuned mechanical properties successfully covered from healthy tissue to colorectal cancer stages. Hydrogels prepared in phosphate-buffered saline or Dulbecco's modified Eagle's medium resulted in different mechanical and swelling properties, although a similar trend was observed for both conditions: thiol-ene systems exhibited higher stiffness and, at the same time, higher swelling capacity than free-radical photopolymerized networks. In terms of biological behavior, three of the substrates showed good cell proliferation rates according to the formation of a confluent monolayer of Caco-2 cells after 14 days of cell culture. Likewise, a characteristic apical-basal polarization of cells was observed for these three hydrogels. These results demonstrate the versatility of the presented platform of biomimetic materials as cell culture scaffolds.
机械微环境在结直肠癌的发展过程中起着至关重要的作用，结直肠癌是一种复杂的疾病，其特征是肿瘤具有异质性且弹性各异。为了设定不同的场景，在此我们描述了基于甲基丙烯酰化明胶（GelMA）的水凝胶的制备和特性，其通过两种不同的机制：自由基光聚合和光引发硫醇-烯反应。在保持强度恒定的情况下，通过施加明确的辐照时间，实现了共价交联支架的精确刚度调节。此外，硫醇化学的引入在低至中等固化时间时显著提高了刚度。这种广泛的精细调节的机械性能成功涵盖了从健康组织到结直肠癌各阶段的范围。在磷酸盐缓冲盐水或杜氏改良 Eagle 培养基中制备的水凝胶具有不同的机械和溶胀性能，尽管两种条件下观察到相似的趋势：硫醇-烯体系比自由基光聚合网络表现出更高的刚度，同时具有更高的溶胀能力。在生物学行为方面，根据细胞培养 14 天后 Caco-2 细胞汇合单层的形成情况，三种底物显示出良好的细胞增殖率。同样，对于这三种水凝胶，观察到细胞具有特征性的顶-基极化。这些结果证明了所提出的仿生材料平台作为细胞培养支架的多功能性。
