Egcg-Cus/Sf Nanofibrous Scaffold Prevent Inflammatory Osteolysis In Macrophages

This study aimed at developing multifunctional biomaterials targeting periprosthetic osteolysis (PPO), a bone-related inflammatory disorder causing total joint arthroplasty (TJA) failure. We engineered a hybrid photothermal nanozyme (EGCG-CuS/SF) comprising silk fibroin (SF) matrices functionalized with (-)-Epigallocatechin-3-gallate (EGCG)-loaded copper sulfide (CuS) nanoclusters. Biocompatibility was assessed via CCK-8 and Calcein-AM/PI assays. Osteoclastic differentiation was evaluated in RANKL-induced bone marrow macrophages (BMMs) using TRAP staining, TRITC-phalloidin and qPCR. Then, an oxidative stress injury and inflammatory model of RAW 264.7 was created by lipopolysaccharide (LPS). Antioxidant effects were validated by qPCR, WB and Reactive Oxygen Species. Furthermore, bulk RNA-seq of the model revealed regulation of some inflammatory signaling cascades. EGCG-CuS/SF demonstrated well-tolerated biocompatibility, with potent anti- osteoclastogenic properties. In LPS-induced macrophage, EGCG-CuS/SF mediated nuclear factor erythroid 2-related factor 2 (Nrf2) facilitating its nuclear translocation and subsequent activation of antioxidative genes. RNA sequencing dataset further indicated EGCG-CuS/SF suppressed multiple inflammatory pathways including NF-κB, MAPK family signaling cascades and Toll−like receptor signaling pathway. In summary, we successfully developed a multifunctional EGCG-CuS/SF scaffold with efficacy against inflammatory osteolysis, providing therapeutic strategies for TJA-related inflammatory bone loss.