Stimulation of macrophage cell lines confined with silica and/or silicon particles and embedded in structured collagen gels.

Abstract

Macrophages encapsulated in composite gels are subjected to a three-dimensional (3D) microenvironment and material-related stimuli that allow modulation of their phenotypes. Herein, 3D collagen fibrillar networks structured with di- or tri-functionalized oligourethanes, including Si-O or Si-Si particles confined therein, are compared regarding their physicochemical properties and material-guided macrophage activation. Gelation kinetics, degradation/swelling, and rheometric results demonstrated that the properties of the composite gels depend on the oligourethane functionalization number (derived from diols/triols and L-Lysine diisocyanate, LDI) and silica incorporation. Human or murine macrophages seeded or encapsulated in the composite gels showed good viability and the adoption of an anti-inflammatory phenotype in response to the silica in the composite gel, showing accelerated gelation when cell culture components are present in the liquid precursors. An increase in cell viability proportional to the storage modulus was observed. ELISA tests strongly suggest that the Si-Si nanoparticles in the composites can antagonize the pro-inflammatory stimulation with lipopolysaccharides (LPS) and interferon-gamma (IFNγ), even promoting an anti-inflammatory response in embedded cells after 24 h. Silicon-doped and crosslinked collagen gels have good potential to modulate macrophage inflammatory response, serving as a 3D immunomodulatory scaffold.