Osteoporosis results in decreased bone mass and insufficient osteogenic function. Existing titanium alloy implants have insufficient osteoinductivity and delayed/incomplete fracture union can occur when used to treat osteoporotic fractures. Copper ions have good osteogenic activity, but their dose-dependent cytotoxicity limits their clinical use for bone implants. In this study, titanium alloy implants functionalized with a TiCu/TiCuN coating by arc ion plating achieved a controlled release of copper ions in vitro for 28 days. The coated alloy was co-cultured with bone marrow mesenchymal stem cells and showed excellent biocompatibility and osteoinductivity in vitro. A further exploration of the underlying mechanism by quantitative real-time polymerase chain reaction and western blotting revealed that the enhancement effects are related to the upregulation of genes and proteins (such as axin2, β-catenin, GSK-3β, p-GSK-3β, LEF1 and TCF1/TCF7) involved in the Wnt/β-catenin pathway. In vivo experiments showed that the TiCu/TiCuN coating significantly promoted osteoporotic fracture healing in a rat femur fracture model, and has good in vivo biocompatibility based on various staining results. Our study confirmed that TiCu/TiCuN-coated Ti promotes osteoporotic fracture healing associated with the Wnt pathway. Because the coating effectively accelerates the healing of osteoporotic fractures and improves bone quality, it has significant clinical application prospects.

Sonodynamic therapy (SDT) is an emerging modality for cancer treatment that induces immunogenic cell death (ICD) through reactive oxygen species (ROS) generation, thereby triggering potent antitumor immunity. However, the hypoxic and glutathione (GSH)-rich tumor microenvironment restricts ROS production, while dense extracellular matrix (ECM) formed by cancer-associated fibroblasts (CAFs) further impedes immune cell infiltration. Here, we developed a hydrogel-based localized delivery platform co-encapsulating the nano-sonosensitizer PCN-224@MnO₂@HA (PMH), and SIS3, a SMAD3 inhibitor. Upon hydrogel-mediated local administration, MnO₂ catalyzes O₂ generation from endogenous hydrogen peroxide while depleting intracellular GSH, thereby amplifying ROS production during SDT. Concurrently, SIS3 reprograms CAFs by blocking TGF-β/SMAD3 signaling, reducing collagen deposition and promoting immune cell infiltration. In an osteosarcoma mouse model, the combination of PMH-mediated SDT with SIS3-induced CAF reprogramming reduced collagen deposition by approximately 50 % and triggered robust antitumor immune responses, which collectively contributed to a 76 % inhibition of tumor growth. Collectively, this study demonstrates a novel CAF-targeted SDT strategy integrating ECM remodeling, ROS enhancement, and localized delivery, offering a promising therapeutic paradigm for solid tumor treatment.

Background: Surgery for bone tumors around the knee often involves extensive resection, making the subsequent prosthetic reconstruction challenging. While carbon fiber-reinforced polyetheretherketone (CF-PEEK) has been widely used in orthopedic implants, its application in tumor-type prosthesis is limited. This study aims to evaluate the feasibility of using 30wt% and 60wt% carbon fiber-reinforced polyetheretherketone (CF30-PEEK and CF60-PEEK) as materials for a redesigned tumor-type knee prosthesis through numerical analysis.Methods: A knee joint model based on CT data was created, and the resection and prosthetic reconstruction were simulated. Three finite element models of the prostheses, representing the initial and updated designs with CoCrMo and CFR-PEEK components, were constructed. Loading conditions during standing and squatting were simulated with forces of 700 N and 2800 N, respectively. Finite element analysis was used to analyze the von Mises stress and stability of all components for each prosthesis type.Results: After improvements in both material and design, the new Type 3 prosthesis showed significantly lower overall stress with stress being evenly distributed. Compared with the initial design, the maximum von Mises stress in Type 3 was reduced by 53.9% during standing and 74.2% during squatting. In the standing position, the maximum stress in the CF30-PEEK femoral component decreased by 57.3% compared with the initial design which was composed of CoCrMo, while the stress in the CF60-PEEK cardan shaft remained consistent. In the squatting position, the maximum stress in the femoral component decreased by 81.9%, and the stress in the cardan shaft decreased by 46.5%.Conclusion: The incorporation of CF30-PEEK effectively transmits forces and reduces stress concentration on the femoral component, while CF60-PEEK in the redesigned cardan shaft significantly reduces stress while maintaining stiffness. The redesigned prosthesis effectively conducts loading force and demonstrates favorable biomechanical characteristics, indicating the promising potential of utilizing CF30-PEEK and CF60-PEEK materials for tumor-type knee prostheses. The findings of this study could provide novel insights for the design and development of tumor-type knee prostheses.

Multiple surface treatment methods for titanium alloy prostheses, widely used in orthopedics, are available; however, these can affect bone integration and regeneration efficiency. This study, through cell and animal experiments, we devised seven bone implant categories of Ti6A14V implants, based on surface preparation and post-processing technology (polishing, sandblasting, fine titanium spraying, coarse titanium spraying, electron beam melting [EBM] printing, selective laser melting [SLM] printing, and post-processed SLM printing) and imaged each microscopic surface structure with a scanning electron microscope (SEM). Mechanical testing revealed excessive post-processing damaged the mechanical properties of the implants. In vitro, human bone marrow mesenchymal stem cells (hBMSCs) were co-cultured with implants, and the morphology of the cells adhering to the implant surface was observed using SEM and confocal laser scanning microscopy. Cell Counting Kit-8 (CCK-8) semi-quantitatively determined cell activity, indirectly reflecting the proliferation of hBMSCs. Alizarin Red (AR) and alkaline phosphatase (ALP) experiments assessed osteogenic differentiation. In vivo, experiments utilized the New Zealand rabbit femoral condyle bone defect model to assess bone regeneration and integration using micro-computed tomography, Van Giesen staining, and Masson staining. We found that 3D-printed implants with regular pore structures were more conducive to hBMSCs' osteogenic differentiation, while the presence of metal powder on SLM-printed implants hindered such differentiation. The post-processed SLM scaffold's surface may have some residual semi-melted powder; however, these powder residues have no significant effect on cell activity and differentiation. Surface treatment (sandblasting and titanium spraying) of planar structures can enhance the hBMSCs' adhesion but do not necessarily promote their differentiation. The framework structure of 3D printing may affect the osteogenic differentiation of hBMSCs and for SLM-printed implants, excessive pursuit of a "powderless" state will damage the mechanical properties of the implant.