Macrophage Polarization Modulated by NF‐κB in Polylactide Membranes‐Treated Peritendinous Adhesion

Abstract Foreign body reactions (FBR) to implants seriously impair tissue‐implant integration and postoperative adhesion. The macrophage, owing to its phenotypic plasticity, is a major regulator in the formation of the inflammatory microenvironment; NF‐κB signaling also plays a vital role in the process. It is hypothesized that NF‐κB phosphorylation exerts a proinflammatory regulator in FBR to polylactide membranes (PLA‐M) and adhesion. First, in vitro and in vivo experiments show that PLA‐M induces NF‐κB phosphorylation in macrophages, leading to M1 polarization and release of inflammatory factors. The inflammatory microenvironment formed due to PLA‐M accelerates myofibroblast differentiation and release of collagen III and MMP2, jointly resulting in peritendinous adhesion. Therefore, JSH‐23 (a selective NF‐κB inhibitor)‐loaded PLA membrane (JSH‐23/PLA‐M) is fabricated by blend electrospinning to regulate the associated M1 polarization for peritendinous anti‐adhesion. JSH‐23/PLA‐M specifically inhibits NF‐κB phosphorylation in macrophages and exhibits anti‐inflammatory and anti‐adhesion properties. The findings demonstrate that NF‐κB phosphorylation has a critical role in PLA‐induced M1 polarization and aggravating FBR to PLA‐M. Additionally, JSH‐23/PLA‐M precisely targets modulation of NF‐κB phosphorylation in FBR to break the vicious cycle in peritendinous adhesion therapy.