After an osteosarcoma resection, the risks of cancer recurrence, postoperative infection, and large bone loss still threaten patients' health. Conventional treatment relies on implanting orthopedic materials to fill bone defects after surgery, but it has no ability of destroying residual tumor cells and preventing bacterial invasion. To tackle this challenge, here, we develop a novel multifunctional implant (SP@MX/GelMA) that mainly consists of MXene nanosheets, gelatin methacrylate (GelMA) hydrogels, and bioinert sulfonated polyetheretherketone (SP) with the purpose of facilitating tumor cell death, combating pathogenic bacteria, and promoting osteogenicity. Because of the synergistic photothermal effects of MXene and polydopamine (pDA), osteosarcoma cells are effectively killed on the multifunctional coatings under 808 nm near-infrared (NIR) irradiation through thermal ablation. After loading tobramycin (TOB), the SP@ MX-TOB/GelMA implants display robust antibacterial properties against Gram-negative/Gram-positive bacteria. More importantly, the multifunctional implants are demonstrated to have superior cytocompatibility and osteogenesis-promoting capability in terms of cell replication, spreading, alkaline phosphatase activity, calcium matrix mineralization, and in vivo osseointegration. Accordingly, such photothermally controlled multifunctional implants not only defeat osteosarcoma cells and bacteria but also intensify osteogenicity, which hold a greatly promising countermeasure for curing postoperative tissue lesion from an osteosarcoma excision.

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As a chronic metabolic disease, diabetes mellitus (DM) creates a hyperglycemic micromilieu around implants, resulting inthe high complication and failure rate of implantation because of mitochondrial dysfunction in hyperglycemia. To address the daunting issue, the authors innovatively devised and developed mitochondria-targeted orthopedic implants consisted of nutrient element coatings and polyetheretherketone (PEEK). Dual nutrient elements, in the modality of ZnO and Sr(OH) 2 , are assembled onto the sulfonated PEEK surface (Zn&Sr-SPEEK). The results indicate the synergistic liberation of Zn 2+ and Sr 2+ from coating massacres pathogenic bacteria and dramatically facilitates cyto-activity of osteoblasts upon the hyperglycemic niche. Intriguingly, Zn&Sr-SPEEK implants are demonstrated to have a robust ability to recuperate hyperglycemia-induced mitochondrial dynamic disequilibrium and dysfunction by means of Dynamin-related protein 1 (Drp1) gene down-regulation, mitochondrial membrane potential (MMP) resurgence, and reactive oxygen species (ROS) elimination, ultimately enhancing osteogenicity of osteoblasts. In vivo evaluations utilizing diabetic rat femoral/tibia defect model at 4 and 8 weeks further confirm that nutrient element coatings substantially augment bone remodeling and osseointegration. Altogether, this study not only reveals the importance of Zn 2+ and Sr 2+ modulation on mitochondrial dynamics that contributes to bone formation and osseointegration, but also provides a novel orthopedic implant for diabetic patients with mitochondrial modulation capability.

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