The effect of heterobifunctional crosslinkers on HEMA hydrogel modulus and toughness

The use of hydrogels in load bearing applications is often limited by insufficient toughness. 2-Hydroxyethyl methacrylate (HEMA) based hydrogels are appealing for translational work, as they are affordable and the use of HEMA is FDA approved. Furthermore, HEMA is photopolymerizable, providing spatiotemporal control over mechanical properties. We evaluated the ability of vinyl methacrylate (VM), allyl methacrylate (AM), and 3-(Acryloyloxy)-2-hydroxypropyl methacrylate (AHPM) to tune hydrogel toughness and Young’s modulus. The crosslinkers were selected due to their heterobifunctionality (vinyl and methacrylate) and similar size and structure to EGDMA, which was shown previously to increase toughness as compared to longer crosslinkers. Vinyl methacrylate incorporation into HEMA hydrogels gave rise to hydrogels with Young’s moduli spanning ranges for ligament to cartilage, with a peak toughness of 519 ± 70 kJ/m3 under physiological conditions. We report toughness (work of extension) as a function of modulus and equilibrium water content for all formulations. The hydrogels exhibited 80%-100% cell viability, which suggests they could be used in tissue engineering applications.

水凝胶（hydrogel）在承重应用中的使用常因韧性不足而受限。以甲基丙烯酸2-羟乙酯（2-Hydroxyethyl methacrylate, HEMA）为基础的水凝胶在转化研究中颇具吸引力，因其成本低廉且HEMA的使用已获美国食品药品监督管理局（FDA）批准。此外，HEMA可光聚合，能够实现力学性能的时空精准调控。本研究评估了甲基丙烯酸乙烯酯（vinyl methacrylate, VM）、甲基丙烯酸烯丙酯（allyl methacrylate, AM）以及3-(丙烯酰氧基)-2-羟丙基甲基丙烯酸酯（3-(Acryloyloxy)-2-hydroxypropyl methacrylate, AHPM）对水凝胶韧性与杨氏模量（Young’s modulus）的调控能力。选取上述交联剂的原因在于，它们具备异双官能团特性（同时含有乙烯基与甲基丙烯酸酯基团），且尺寸与结构与乙二醇二甲基丙烯酸酯（EGDMA）相近——既往研究表明，相较于长链交联剂，EGDMA可提升水凝胶韧性。将甲基丙烯酸乙烯酯掺入HEMA基水凝胶后，所得材料的杨氏模量覆盖了韧带至软骨的模量区间，在生理条件下的峰值韧性可达519 ± 70 kJ/m³。本研究报告了所有配方的韧性（拉伸功）随模量与平衡含水率的变化规律，该类水凝胶的细胞存活率达80%~100%，表明其可应用于组织工程领域。