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.