Dynamic Slide-Ring Hydrogels with Dityrosine-Driven pH-Responsive Fluorescence: Enabling 3D Printing, Enhanced Drug Delivery and Regenerative Therapy.

Abstract

The development of intelligent hydrogels with multifunctional capabilities holds great promise for advancing medical applications. In this work, we developed a dynamic slide-ring supramolecular hydrogel with dual molecular innovations: a dityrosine (DY)-driven pH-responsive fluorescence core in four-arm PEG (4A-PD) and Arginine-Glycine-Aspartic acid peptide (RGD) peptide-functionalized hyperbranched polyglycerol (HPG)-modified α-cyclodextrin (CHR) for enhanced cell adhesion and drug loading. The host-guest interactions between 4A-PD and CHR form a network with shear-thinning, rapid self-healing, and UV-triggered covalent stabilization, enabling room-temperature extrusion-based 3D printing. The printed constructs exhibit high shape fidelity and porous architectures that promote RGD-mediated cell adhesion and proliferation. The DY core imparts the hydrogel with pH-dependent blue fluorescence (emission peak: 400 nm), allowing real-time microenvironmental monitoring. HPG modification of α-CD significantly enhances the drug-loading capacity, demonstrated by the sustained release of tobramycin (TOB) for effective infection control. In a full-thickness infected rat wound model, the TOB-loaded hydrogel accelerates wound closure (97.67% ± 0.56% by day 14), promotes collagen deposition, and modulates inflammation (reduced IL-6, increased IL-10), while enhancing angiogenesis. This multifunctional hydrogel integrates 3D printing, drug delivery, and responsive sensing, offering a versatile platform for regenerative medicine.