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Peptides from Phage Display Library Modulate Gene Expression in Mesenchymal Cells and Potentiate Osteogenesis in Unicortical Bone Defects
Published on: December 10, 2010
Sulfonated polyetheretherketone enriched with MXene V2C promotes bone formation via WNT/β-catenin signaling in bone
Shengjie Wang1, Wei Liu1, Chao Yang1
1Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai 200233, China.
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.

