Glucose-primed PEEK orthopedic implants for antibacterial therapy and safeguarding diabetic osseointegration.

Diabetic infectious microenvironment (DIME) frequently leads to a critical failure of osseointegration by virtue of its main peculiarities including typical hyperglycemia and pathogenic infection around implants. To address the plaguing issue, we devise a glucose-primed orthopedic implant composed of polyetheretherketone (PEEK), Cu-chelated metal-polyphenol network (hauberk coating) and glucose oxidase (GOx) for boosting diabetic osseointegration. Upon DIME, GOx on implants sostenuto consumes glucose to generate H2O2, and Cu liberated from hauberk coating catalyzes the H2O2 to highly germicidal •OH, which massacres pathogenic bacteria through photo-augmented chemodynamic therapy. Intriguingly, the catalytic efficiency of the coating gets greatly improved with the turnover number (TON) of 0.284 s-1. Moreover, the engineered implants exhibit satisfactory cytocompatibility and facilitate osteogenicity due to the presence of Cu and osteopromotive polydopamine coating. RNA-seq analysis reveals that the implants enable to combat infections and suppress pro-inflammatory phenotype (M1). Besides, in vivo evaluations utilizing infected diabetic rat bone defect models at week 4 and 8 authenticate that the engineered implants considerably elevate osseointegration through pathogen elimination, inflammation dampening and osteogenesis promotion. Altogether, our present study puts forward a conceptually new tactic that arms orthopedic implants with glucose-primed antibacterial and osteogenic capacities for intractable diabetic osseointegration.

Photonic double-network hydrogel dressings for antibacterial phototherapy and inflammation regulation in the general management of cutaneous regeneration.

The treatment of festering pathogenic bacteria-induced skin wounds with increased inflammation is an ongoing challenge. The traditional antibacterial photothermal therapy always results in localized hyperthermia (over 50 °C), which inevitably delays tissue recovery. To address this serious issue, we devise a novel photonic hydrogel by integrating urchin-like Bi2S3 nano-heterojunctions (nano-HJs) into double-network hydrogels for infected skin regeneration. The synergy of NIR-triggered heat and ROS enables the hydrogels to achieve a rapid germicidal efficacy against bacteria within 15 min at mild temperature (below 50 °C). In vitro cell analysis results revealed that the photonic hydrogels exhibit superior cytocompatibility even after NIR illumination. More importantly, an in vivo study demonstrated that the photonic hydrogel dressings have a robust ability of accelerating contagious full-thickness wound regeneration through debriding abscesses, eliminating pathogens, improving collagen deposition, promoting angiogenesis, and adjusting the inflammation state. This photonic hydrogel system provides a general management strategy for the remedy of infectious wounds, where the incorporation of nano-HJs endows the hydrogels with the photodisinfection ability; in addition, the multifunctional hydrogels alleviate the damage from overwhelming heat towards surrounding tissues during phototherapy and steer the inflammation during the process of tissue regeneration. Accordingly, this work highlights the promising application of the photonic hydrogels in conquering refractory pathogen-invaded infection.

Nutrient Element Decorated Polyetheretherketone Implants Steer Mitochondrial Dynamics for Boosted Diabetic Osseointegration.

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 Zn2+ and Sr2+ 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 Zn2+ and Sr2+ 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.

MXene-Based Hydrogels Endow Polyetheretherketone with Effective Osteogenicity and Combined Treatment of Osteosarcoma and Bacterial Infection.

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.

Two-dimensional MXene/cobalt nanowire heterojunction for controlled drug delivery and chemo-photothermal therapy.

Two-dimensional (2D) MXene nanomaterials have explored as a great potential candidate for tumor therapy during recent decades, especially for photothermal therapeutic applications. However, MXene-based drug-carriers cannot be elaborately controlled in cancer therapy. To solve the problem, a heterostructured titanium carbide-cobalt nanowires (Ti3C2-CoNWs) nanocarrier is developed for synergetic anticancer with magnetic controlling ability, dual stimuli-responsive drug release, and chemo-photothermal therapy. The structure, drug loading/release behavior, magnetic controlling capacity, photothermal performance, and synergistic therapeutic efficiency of the Ti3C2-CoNWs nanocarrier heterojunction are investigated. The heterostructured Ti3C2-CoNWs nanocarrier exhibits excellent photothermal conversion efficiency under 808 nm laser irradiation and high drug loading ability (225.05%). The doxorubicin (DOX) release behavior can be triggered by acid pH value (4-6) or near-infrared (NIR) irradiation. The Ti3C2-CoNWs nanocarrier heterojunction with synergistic chemo-photothermal therapeutic effect exhibits strong lethality for cancer cells than that of chemotherapy or photothermal therapy (PTT) alone. Therefore, Ti3C2-CoNWs nanocarrier heterojunction will be a promising choice for improving the efficiency of cancer treatment.