Radical‐Mediated, Substrate‐Independent Fabrication of Hybrid Solid–Hydrogel Materials With Tunable Crosslinking: An Initiator‐ and Crosslinker‐Free Approach

Abstract Achieving robust, cytocompatible bonding of hydrogels to solid substrates remains a long‐lasting challenge in the development of hybrid solid–hydrogel (HSH) systems for biomedical applications. Current strategies for hydrogel–solid bonding suffer from the complexity of processes, toxicity from residual crosslinkers, and substrate dependency; issues that hinder clinical adoption of HSH structures (HSHs). Overcoming these impediments, a dry, reagent‐free strategy is presented to create radical‐rich interlayers that enable initiator‐ and crosslinker‐free covalent attachment of hydrogels for the fabrication of robust HSHs. Evidence is provided in which long‐lived radicals embedded in ion‐assisted plasma polymerized coatings simultaneously drive hydrogel anchoring and in situ crosslinking on diverse non‐polymeric substrates, including titanium, stainless steel, and glass. GelMA, chitosan, and PVA‐Tyr hydrogels are immobilized with high stability, with coatings remaining intact after two months in aqueous media. Tuning the substrate bias voltage modulates radical concentration, enabling precise control over hydrogel thickness and crosslinking density with no need for extra reagents and/or crosslinkers. Cytocompatibility is confirmed with human mesenchymal stem cells and macrophages, with negligible inflammatory activation detected under the tested conditions. To showcase one application among many, fibroblasts on GelMA‐based HSHs exhibited enhanced early attachment, spreading, and proliferation, supporting their application in promoting soft tissue integration. This substrate‐independent, additive‐ and initiator‐free strategy embodies high‐quality‐by‐design principles, enabling a universal and scalable platform for the fabrication of HSH systems, particularly suited for applications requiring seamless integration between soft and hard materials, such as biomedical coatings, tissue‐interfacing constructs, and next‐generation soft robotics.