可注射水凝胶已被广泛用作有前途的治疗支架,用于广泛的生物医学应用。如组织再生和药物输送。然而,它们的低断裂韧性和脆性往往限制了它们的应用范围。双网(DN)水凝胶,由独立交联的刚性和延性聚合物网络组成,已被提议作为替代技术来补偿水凝胶的弱机械性能。然而,一些挑战仍然存在,例如DN形成的复杂而耗时的过程,以及控制DN水凝胶力学性能的困难。在这项研究中,我们介绍一个简单的,快速,和可控方法通过Fenton和酶介导的双重反应制备由丙烯酰胺(AAm)和4臂-PPO-PEO-酪胺(TTA)组成的原位可交联可注射DN水凝胶。通过改变芬顿试剂的浓度,DN水凝胶快速形成,凝胶速率可控。重要的是,DN水凝胶的抗压强度增加了13倍,拉伸强度增加了14倍,与单网络水凝胶相比。机械性能,弹性,DN水凝胶的可塑性也可以通过简单地改变制备条件来调节,包括交联密度和试剂浓度。在低交联剂浓度(<0.05wt%)下,塑料DN水凝胶拉伸到超过6,500%,而高交联剂浓度(≥0.05wt%)诱导完全弹性水凝胶,没有滞后。此外,DN水凝胶具有快速的自恢复和高度增强的附着力,可以进一步应用于可穿戴设备。此外,用DN水凝胶处理的人真皮成纤维细胞保留了活力,证明了交联系统的生物相容性。因此,我们预计,双Fenton/酶介导的可交联DN水凝胶提供了巨大的潜力作为先进的生物材料应用于硬组织再生和替代。
Injectable hydrogels have been extensively used as promising therapeutic scaffolds for a wide range of biomedical applications, such as tissue regeneration and drug delivery. However, their low fracture toughness and brittleness often limit their scope of application. Double-network (DN) hydrogel, which is composed of independently cross-linked rigid and ductile polymer networks, has been proposed as an alternative technique to compensate for the weak mechanical properties of hydrogels. Nevertheless, some challenges still remain, such as the complicated and time-consuming process for DN formation, and the difficulty in controlling the mechanical properties of DN hydrogels. In this study, we introduce a simple, rapid, and controllable method to prepare in situ cross-linkable injectable DN hydrogels composed of acrylamide (AAm) and 4-arm-PPO-PEO-tyramine (TTA) via dual Fenton- and enzyme-mediated reactions. By varying the concentration of Fenton\'s reagent, the DN hydrogels were rapidly formed with controllable gelation rate. Importantly, the DN hydrogels showed a 13-fold increase in compressive strength and a 14-fold increase in tensile strength, compared to the single network hydrogels. The mechanical properties, elasticity, and plasticity of DN hydrogels could also be modulated by simply varying the preparation conditions, including the cross-linking density and reagent concentrations. At low cross-linker concentration (<0.05 wt %), the plastic DN hydrogel stretched to over 6,500%, whereas high cross-linker concentration (≥0.05 wt %) induced fully elastic hydrogels, without hysteresis. Besides, DN hydrogels were endowed with rapid self-recovery and highly enhanced adhesion, which can be further applied to wearable devices. Moreover, human dermal fibroblasts treated with DN hydrogels retained viability, demonstrating the biocompatibility of the cross-linking system. Therefore, we expect that the dual Fenton-/enzyme-mediated cross-linkable DN hydrogels offer great potential as advanced biomaterials applied for hard tissue regeneration and replacement.