Troncoso-Afonso Lara, Henríquez-Banegas Yolany M, Vinnacombe-Willson Gail A, Gutierrez Junkal, Gallastegui Gorka, Liz-Marzán Luis M, García-Astrain Clara
CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), 20014 Donostia-San Sebastián, Spain.
Department of Applied Chemistry, University of the Basque Country (UPV/EHU), 20018 Donostia-San Sebastian, Spain.
Biomater Sci. 2025 Apr 16. doi: 10.1039/d4bm01529k.
3D cell culture models allow the study of the biomolecular processes underlying pathophysiological conditions by mimicking tissues and organs. Despite significant progress in creating such 3D architectures, studying cell behaviour in these systems still poses some challenges due to their heterogeneity and complex geometry. In this context, surface-enhanced Raman spectroscopy (SERS) can be implemented for molecular detection in biological settings with high sensitivity. The incorporation of SERS sensors in 3D models can thus lead to powerful platforms to study cellular response to therapeutics, metabolic pathways, signaling, and cell-cell communication events. Here, we introduce a library of plasmonic hydrogels that can be orthogonally photo-crosslinked thiol-ene click chemistry and identify the main physicochemical factors accounting for their SERS performance. Using hydrogel-forming polymers such as gelatin, alginate, and carboxymethylcellulose modified with complementary thiol and norbornene groups, we created hydrogels with tailored chemical backbones. We identified swelling, porosity, and chemical composition as crucial factors determining their potential to detect different molecules by SERS. We additionally assessed their biocompatibility and printability, to ensure that these hydrogels meet the requirements for their use as 3D cellular scaffolds, showing their potential for real-time and detection of biorelevant metabolites.
3D细胞培养模型通过模拟组织和器官，使得对病理生理状况下潜在的生物分子过程的研究成为可能。尽管在创建此类3D结构方面取得了重大进展，但由于这些系统的异质性和复杂几何形状，研究其中的细胞行为仍然面临一些挑战。在这种情况下，表面增强拉曼光谱（SERS）可用于在生物环境中进行高灵敏度的分子检测。因此，将SERS传感器整合到3D模型中可形成强大的平台，用于研究细胞对治疗药物的反应、代谢途径、信号传导以及细胞间通讯事件。在此，我们介绍了一个可通过硫醇-烯点击化学进行正交光交联的等离子体水凝胶库，并确定了影响其SERS性能的主要物理化学因素。使用诸如用互补硫醇和降冰片烯基团修饰的明胶、藻酸盐和羧甲基纤维素等形成水凝胶的聚合物，我们制备了具有定制化学主链的水凝胶。我们确定了溶胀、孔隙率和化学成分是决定其通过SERS检测不同分子能力的关键因素。我们还评估了它们的生物相容性和可打印性，以确保这些水凝胶满足用作3D细胞支架的要求，显示出它们在实时检测生物相关代谢物方面的潜力。
