Advanced thermoplastic materials, such as polyether-ether-ketone (PEEK) and highly cross-linked polyethylene (HXLPE), have been increasingly used as orthopaedic implant materials. Similar to other implants, PEEK-on-HXLPE prostheses produce debris from polymer wear that may activate the immune response, which can cause osteolysis, and ultimately implant failure. In this study, we examined whether the anti-inflammatory properties of zinc oxide nanoparticles (ZnO NPs) could attenuate polymer wear particle-induced inflammation. RAW264.7 ​cells were cultured with PEEK or PE particles and gradient concentrations of ZnO NPs. Intracellular mRNA expression and protein levels of pro-inflammatory factors TNF-α, IL-1β, and IL-6 were detected. An air pouch mouse model was constructed to examine the inflammatory response and expression of pro-inflammatory factors in vivo. Furthermore, an osteolysis rat model was used to evaluate the activation of osteoclasts and destruction of bone tissue induced by polymer particles with or without ZnO NPs. Protein expression of the MEK-ERK-COX-2 pathway was also examined by western blotting to elucidate the mechanism underlying particle-induced anti-inflammatory effects. ZnO NPs (≤50 ​nm, 5 ​μg/mL) showed no obvious cytotoxicity and attenuated PEEK or PE particle-induced inflammation and inflammatory osteolysis by reducing MEK and ERK phosphorylation and decreasing COX-2 expression. ZnO NPs (≤50 ​nm, 5 ​μg/mL) attenuated polymer wear particle-induced inflammation via regulation of the MEK-ERK-COX-2 axis. Further, ZnO NPs reduced bone tissue damage caused by particle-induced inflammatory osteolysis. Polymer wear particles can induce inflammation and osteolysis in the body after arthroplasty. ZnO NPs attenuated polymer particle-induced inflammation and inflammatory osteolysis. Topical use of ZnO NPs and blended ZnO NP/polymer composites may provide promising approaches for inhibiting polymer wear particle-induced inflammatory osteolysis, thus expanding the range of polymers used in joint prostheses.

Gene therapy offers an ideal potential treatment strategy for osteoarthritis (OA). However, the safe and efficient delivery of therapeutic genes remains highly challenging because of the inactivation in direct delivery of miRNA, low transfection efficiency, and a short half‐life. This study introduced a gene therapy strategy using mesenchymal stem cells (MSCs) as a gene delivery platform and achieved the sustained delivery of therapeutic genes via engineered MSCs‐derived extracellular vesicles (EVs). The miRNA‐874‐3p is combined with an exosome‐targeting motif and transfected into bone marrow mesenchymal stem cells (BMSCs). The BMSCs ^motif+miR874 are then seeded onto hydrogel microspheres, creating the BMSC ^motif+miR874 /MS system for OA treatment. In vitro experiments demonstrated that miRNA‐874‐3p not only alleviated inflammation and oxidative stress‐induced damage to chondrocytes by downregulating the NF‐κB signaling pathway, thereby rejuvenating chondrocytes, but also promoted chondrogenesis in the inflammatory microenvironment. Furthermore, the engineered BMSCs in the system demonstrated prolonged retention in vivo, thereby enabling the sustained delivery of the therapeutic gene, miRNA‐874‐3p, over an extended duration. In the rat OA model, BMSC ^motif+miR874 /MS successfully delivered miRNA‐874‐3p to the articular cartilage and effectively alleviated cartilage degeneration. In conclusion, this EVs‐mediated therapeutic gene delivery approach enables miRNA‐based gene therapy a viable alternative to surgery for OA treatment and provides a novel option for gene therapy.

Osteochondral lesions represent a major clinical challenge, especially in the elderly. Traditional treatment strategies, such as arthroplasty or tissue engineering, have limitations and drawbacks. In this study, we presented a new treatment concept for the application of an innovative porous bioactive prosthesis with regenerative activity for the treatment of osteoarticular lesions. For regenerative activity, we fabricated chitosan/mesoporous silica nanoparticles (CS/MSNs) composite microspheres via the microfluidic method as a dual-factor carrier for the sequential release of platelet-derived growth factor BB (PDGF-BB) and kartogenin (KGN). We then integrated the factor carrier and a nondegradable polyetheretherketone (PEEK) scaffold through a surface modification technique to construct the porous sulfonated PEEK (SPK) @polydopamine (polydopamine)-CS/MSNs scaffold. We systematically evaluated the biocompatibility and biofunctionality of the SPK@PDA-CS/MSNs scaffold and implanted the scaffold in an in vivo cartilage defect model in rabbits. These results suggest that the SPK@PDA-CS/MSNs scaffold is biocompatible, promotes cell migration, enhances chondrogenic differentiation of BMSCs in vitro, and promotes cartilage regeneration in vivo. The porous bioactive prosthesis with regenerative activity presented first in this study may comprise a new therapeutic concept for osteoarticular lesions.