Sulfonated polyetheretherketone enriched with MXene V2C promotes bone formation via WNT/β-catenin signaling in bone marrow mesenchymal stem cells

Abstract

Prosthetic loosening represents a catastrophic postoperative complication in artificial joint replacement, resulting in severe patient morbidity and substantial healthcare costs. This investigation aimed to develop a novel strategy for preventing prosthetic loosening. Two-dimensional MXene V₂C nanosheets were synthesized and subsequently immobilized onto three-dimensional porous sulfonated polyetheretherketone (SPEEK) surfaces with polydopamine (PDA) to form V₂C-PDA@SPEEK (Abbrev. V₂C-PS). The biocompatibility was systematically evaluated using rat bone marrow mesenchymal stem cells (rBMSCs) and murine models. The osteogenic differentiation potential of V₂C-PS was assessed through real-time PCR analysis, Alkaline phosphatase (ALP) staining, and Alizarin Red staining. The in vivo osteogenic capacity of V₂C-PS surrounding the implant material was evaluated in rat femoral models using micro-CT analysis, biomechanical pull-out testing, sequential fluorescent labeling of newly formed bone, and Van Gieson staining. The molecular mechanisms underlying V₂C-PS -mediated osteogenic differentiation of rBMSCs were investigated both in vitro and in vivo using chemical inhibitors, β-catenin shRNA lentiviral silencing, and β-catenin mRNA lentiviral overexpression. The results demonstrated that V₂C-PS exhibited excellent biocompatibility. Quantitative analysis revealed substantial upregulation (p < 0.05) of critical osteogenic markers, including RUNX2 (4.4-fold), COL-1 (5.7-fold), OCN (3.3-fold), BMP-2 (4.4-fold), OPN (3.1-fold), BSP (3.3-fold), ON (4.3-fold), and OSX (2.83-fold), in the 25V₂C-PS treatment group compared to PS group. The bone parameters were also remarkably enhanced in the 25V₂C-PS group (BMD increased by 241 %, bone-implant contact by 159 %, BV/TV by 225 %, Tb.N by 281 %, Tb.Th by 214 %, maximum pull-out force by 250 %, and Tp.Sp decreased by 33 %). Furthermore, V₂C-PS were found to enhance rBMSC osteogenic differentiation through activation of the Wnt/β-catenin signaling pathway. This study presents a promising approach for preventing orthopedic prosthetic loosening and demonstrates significant potential for clinical translation.