ECM–oligourethene–silica hydrogels as a local drug release system of dexamethasone for stimulating macrophages

Abstract

Hydrogels based on an extracellular matrix (ECM) capable of delivering therapeutics in a controlled manner represent a platform to guide tissue regeneration. This work reports a novel approach wherein the incorporation of silica particles (SiP) inside ECM hydrogels supports the loading and releasing of dexamethasone (Dex). The biocomposite hydrogels, derived from porcine small intestine submucosa (SIS), water-soluble oligourethanes (PPU synthetized from polyethylene glycol and hexamethylene-diisocyanate) and SiP, delivered Dex at pH 7.4 and 37 °C in vitro. In this regard, the SiP (0, 5 and 15 wt%) accelerated the collagen polymerization and modified the collagen network structural parameters, while the oligourethane crosslinking regulated the mechanics and degradation of the material. The biocomposite hydrogels containing 15 wt% SiP showed controlled release of Dex for 11 days, obtaining a 79% release efficiency. As a consequence, the delivery of Dex from biocomposites was capable of enhancing cell metabolic activity and TGF-β1 secretion by macrophages. These composite collagen hydrogels combine structures and properties that make them promising templates for loading and delivering Dex that can modulate the macrophage response in a soft tissue engineering context.