Laser-based in situ embedding of metal nanoparticles into bioextruded alginate hydrogel tubes enhances human endothelial cell adhesion

Alginate is a widely used hydrogel in tissue engineering owing to its simple and non-cytotoxic gelation process, ease of use, and abundance. However, unlike hydrogels derived from mammalian sources such as collagen, alginate does not contain cell adhesion ligands. Here, we present a novel laser ablation technique for the in situ embedding of gold and iron nanoparticles into hydrogels. We hypothesized that integration of metal nanoparticles in alginate could serve as an alternative material because of its chemical biofunctionalization ability (coupling of RGD ligands) to favor cell adhesion. Cytocompatibility and biofunctionality of the gels were assessed by cell culture experiments using fibroblasts and endothelial cells. Nanoparticles with an average particle size of 3 nm (gold) and 6 nm (iron) were generated and stably maintained in alginate for up to 6 months. Using an extrusion system, several centimeter-long alginate tubes with an outer diameter of approximately 3 mm and a wall thickness of approximately 150 μm were manufactured. Confocal microscopy revealed homogeneously distributed nanoparticle agglomerates over the entire tube volume. Endothelial cells seeded on iron-loaded gels showed significantly higher viability and an increased degree of spreading, and the number of attached cells was also elevated in comparison to the control and gold-loaded alginates. We conclude that laser-based in situ integration of iron nanoparticles (-0.01 wt.%) in alginate is a straightforward method to generate composite materials that favor the adhesion of endothelial cells. In addition, we show that nanoparticle integration does not impair the alginate's gelation and 3D biofabrication properties.