Intermuscular Septum Delivery of High-Mechanical Injectable Magnetic Hydrogels to Improve Muscle Atrophy.

Abstract

Injectable hydrogels often lack sufficient mechanical robustness for long-term function under physiological loading, limiting their application in musculoskeletal repair. Inspired by natural soft matter, we developed a hierarchical reinforcement strategy that combines sliding-ring structures with rigid magnetic nanocomposite microdomains. Through self-assembly driven by chelation and hydrogen bonding, hydrophobic drugs and magnetic nanoparticles formed microphase units within the hydrogel network, resulting in an injectable magneto-responsive platform (0.2F@UA-PC) with exceptional mechanical properties, including >1100% tensile strain, high toughness (3.12 MJ/m³), and compressive strength of 6 MPa at 90% strain without rupture. In a sciatic nerve transection-induced muscle atrophy model, intermuscular septum injection enabled localized mechanical stimulation and sustained drug release, significantly enhancing myofiber regeneration (<i>p</i> < 0.01 vs controls). This study presents a robust biomaterial platform for tissue engineering in mechanically demanding environments and provides insights into the role of localized mechanical cues in regenerative medicine.