Ibuprofen Conjugated Epsilon-poly-l-lysine Methacrylate Hydrogel Modulates Macrophage Polarization and Mitigates Inflammation In Vivo

Epsilon-poly-l-lysine (EPL) is widely used in many biomedical applications due to its excellent antibacterial activity and good biocompatibility. In this study, we report an approach of carbodiimide chemistry to graft water-soluble EPL with hydrophobic drug ibuprofen (IBU) and then modify the obtained IBU-EPL conjugate with methacrylic anhydride (MA) to prepare IBU-EPL-MA. The IBU-EPL-MA was of good photo-cross-linkability to form hydrogel with sustained drug release and good blood compatibility. It significantly inhibited bacterial growth, promoted lipopolysaccharide (LPS)-induced macrophage polarization to the M2-like phenotype, and reduced reactive oxygen species (ROS) levels in vitro. The IBU-EPL-MA hydrogel elicited milder foreign body response (FBR) as evidenced by reduced fibrous capsule thickness, increased macrophage polarization to M2-like phenotype, and less extent of blood vessel formation surrounding implants in a mouse subcutaneous model. This study provides insights into multifunctional EPL-based biomaterials with antibacterial, anti-inflammatory, and sustained drug release capabilities that expand potential biomedical applications.