Abstract
Metal ions provide multifunctional signals for cell and tissue functions, including regeneration. Inspired by metal-organic frameworks (MOFs), nanosized silk protein aggregates with a high negative charge density are used to form stable silk-magnesium ion complexes. Magnesium ions (Mg ions) are added directly to silk nanoparticle solutions, inducing gelation through the formation of silk-Mg coordination complexes. The Mg ions are released slowly from the nanoparticles through diffusion, with sustained release via tuning the degradation or dissolution of the nanosized silk aggregates. Studies in vitro reveal a dose-dependent influence of Mg ions on angiogenic and anti-inflammatory functions. Silk-Mg ion complexes in the form of hydrogels also stimulate tissue regeneration with a reduced formation of scar tissue in vivo, suggesting potential utility in tissue regeneration.