Triple Modification of Alginate Hydrogels by Fibrin Blending, Iron Nanoparticle Embedding, and Serum Protein‐Coating Synergistically Promotes Strong Endothelialization

Abstract Stent therapy can reduce both morbidity and mortality of chronic coronary stenosis and acute myocardial infarction. However, delayed re‐endothelialization, endothelial dysfunction, and chronic inflammation are still unsolved problems. Alginate hydrogels can be used as a coating for stent surfaces; however, complete and fast endothelialization cannot be achieved. In this study, alginate hydrogels are modified by fibrin blending, iron nanoparticle (Fe‐NP) embedding, and serum protein coating (SPC) while surface properties and endothelialization capacity are monitored. Only a triple, synergetic modification of the alginate coating by simultaneous I) fibrin blending, II) Fe‐NP addition complemented by III) SPC is found to significantly improve endothelial cell viability (live–dead‐staining) and proliferation (WST‐8 assay). These conditions yield formation of closed endothelial cell monolayers and an up to threefold increase (p < 0.01) in viability, while, interestingly, no effect is found when the modifications (I)–(III) are conducted individually. This synergetic effect is attributed to an accumulation of agglomerated Fe‐NP and serum proteins along fibrin fibers, observed via laser scanning microscopy tracking nanoparticle scattering and tetramethylrhodamine (TRITC)‐albumin fluorescence. These synergetic effects can pave the way toward a novel strategy for the modification of various hydrogel‐based biomaterials and biomaterial coatings.