different available therapies, stent therapy is able to reduce both the morbidity and mortality of coronary heart disease and its acute complication, the myocardial infarction. Therefore, stent therapy has become the primary therapy for acute ST-elevation myocardial infarction. [2] Nevertheless, instent-restenosis resulting from thromboembolic events, neointimal hyperplasia, or neoatherosclerosis is still the limiting factor of successful invasive stent therapy. [3,4] The underlying pathomechanism of these failures includes delayed re-endothelialization and endothelial dysfunction which are further aggravated by hypersensitivity reactions to synthetic polymers resulting in chronic inflammation. [1,5] Therefore, the development of a biocompatible stent device enhancing functional endothelialization is highly required. Biological polymers, especially, are attracting more and more interest. Among those are protein-based polymers like fibrin [6] or polysaccharide-based polymers like alginic acid. [7] Alginate hydrogels have been suggested as biological stentcoatings since they have been characterized by high biocompatibility and a so-called "non-fouling" effect. [8] Due to the absence of any adhesive structures and high surface wettability, alginate 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.