Stimuli-responsive, methyl cellulose-based, interpenetrating network hydrogels: Non-covalent design, injectability, and controlled release

Abstract

This paper demonstrates the molecular design of stimuli-responsive, methyl cellulose-based, injectable hydrogels consisting of two orthogonal supramolecular networks. Rapidly injectable hydrogels that undergo autonomous gelation without permanent cross-links are crucial for biomedical applications due to minimal invasiveness, adaptability to irregular target sites, and precise spatiotemporal control. However, they often lack sufficient mechanical strength, physicochemical stability, and high biocompatibility. Herein, we develop a molecular design of a non-covalent double-network system by strategically incorporating specific host–guest cross-linking sites into a thermo-responsive network, which is reinforced by interpenetration with a cellulose-based network via their sequential formation. The resulting hydrogel, composed of non-cytotoxic materials, demonstrates high cell viability (>90 %) until its concentration of 25 mg mL⁻¹, rapid self-healing within 1 min, suitable injection pressure (1.1 kPa), and drug release behavior controllable by heat, chemicals, or ultrasound. Therefore, the hydrogel could be loaded with diclofenac (3.5 mg mL⁻¹), a non-steroidal anti-inflammatory drug, and treat osteoarthritis when injected into a rat knee joint, achieving results comparable to those in a control group without osteoarthritis. This system thus holds promise for the delivery of various drugs as a responsive vector, offering synergistic effects via the inclusion of functional polymeric networks or exogenous additives for bio- or environment-related applications.