Traditional antibiotic treatment has limited efficacy for the drug-tolerant bacteria present in biofilms because of their unique metabolic conditions in the biofilm infection microenvironment. Modulating the biofilm infection microenvironment may influence the metabolic state of the bacteria and provide alternative therapeutic routes. In this study, photodynamic therapy is used not only to eradicate methicillin-resistant Staphylococcus aureus biofilms in the normoxic condition, but also to potentiate the hypoxic microenvironment, which induces the anaerobic metabolism of methicillin-resistant Staphylococcus aureus and activates the antibacterial activity of metronidazole. Moreover, the photodynamic therapy-activated chemotherapy can polarize the macrophages to a M2-like phenotype and promote the repair of the biofilm infected wounds in mice. This biofilm infection microenvironment modulation strategy, whereby the hypoxic microenvironment is potentiated to synergize photodynamic therapy with chemotherapy, provides an alternative pathway for efficient treatment of biofilm-associated infections.
Dental implants are widely used in the field of oral restoration, but there are still problems leading to implant failures in clinical application, such as failed osseointegration, marginal bone resorption, and peri-implantitis, which restrict the success rate of dental implants and patient satisfaction. Poor osseointegration and bacterial infection are the most essential reasons resulting in implant failure. To improve the clinical outcomes of implants, many scholars devoted to modifying the surface of implants, especially to preparing different physical and chemical modifications to improve the osseointegration between alveolar bone and implant surface. Besides, the bioactive-coatings to promote the adhesion and colonization of ossteointegration-related proteins and cells also aim to improve the osseointegration. Meanwhile, improving the anti-bacterial performance of the implant surface can obstruct the adhesion and activity of bacteria, avoiding the occurrence of inflammation related to implants. Therefore, this review comprehensively investigates and summarizes the modifying or coating methods of implant surfaces, and analyzes the ossteointegration ability and anti-bacterial characteristics of emerging functional coatings in published references.
The formation of bacterial biofilms closely associates with infectious diseases. Until now, precise diagnosis and effective treatment of bacterial biofilm infections are still in great need. Herein, a novel multifunctional theranostic nanoplatform based on MnO 2 nanosheets (MnO 2 NSs) has been designed to achieve pH-responsive dual-mode imaging and hypoxia-relief-enhanced antimicrobial photodynamic therapy (aPDT) of bacterial biofilm infections. In this study, MnO 2 NSs were modified with bovine serum albumin (BSA) and polyethylene glycol (PEG) and then loaded with chlorin e6 (Ce6) as photosensitizer to form MnO 2 -BSA/PEG-Ce6 nanosheets (MBP-Ce6 NSs). After being delivered into the bacterial biofilm-infected tissues, the MBP-Ce6 NSs could be decomposed in acidic biofilm microenvironment and release Ce6 with Mn 2+ , which subsequently activate both fluorescence (FL) and magnetic resonance (MR) signals for effective dual-mode FL/MR imaging of bacterial biofilm infections. Meanwhile, MnO 2 could catalyze the decomposing of H 2 O 2 in biofilm-infected tissues into O 2 and relieve the hypoxic condition of biofilm, which significantly enhances the efficacy of aPDT. An in vitro study showed that MBP-Ce6 NSs could significantly reduce the number of methicillin-resistant S taphylococcus aureus (MRSA) in biofilms after 635 nm laser irradiation. Guided by FL/MR imaging, MRSA biofilm-infected mice can be efficiently treated by MBP-Ce6 NSs-based aPDT. Overall, MBP-Ce6 NSs not only possess biofilm microenvironment-responsive dual-mode FL/MR imaging ability but also have significantly enhanced aPDT efficacy by relieving the hypoxia habitat of biofilm, which provides a promising theranostic nanoplatform for bacterial biofilm infections.
Efficient treatment of chronic lung infections caused by Pseudomonas aeruginosa biofilms is a great challenge because of drug tolerance and immune evasion issues. Here, we develop ultrasound-responsive catalytic microbubbles with biofilm elimination and immune activation properties to combat chronic lung infection induced by P. aeruginosa biofilms. In these microbubbles, piperacillin and Fe 3 O 4 nanoparticles form a drug-loaded shell surrounding the air core. Under ultrasound stimulation, the microbubbles can physically disrupt the structure of biofilms and enhance the penetration of both Fe 3 O 4 nanoparticles and piperacillin into the biofilm. Then, Fe 3 O 4 nanoparticles chemically degrade the biofilm matrix and kill the bacteria with the assistance of piperacillin. Fe 3 O 4 nanoparticles can activate the immune response for biofilm elimination by polarizing macrophages into a pro-inflammatory phenotype. These ultrasound-responsive catalytic microbubbles efficiently treat chronic lung infections in a mouse model by combining physical/chemical/antibiotic biofilm elimination and immune activation, thus providing a promising strategy for combating bacterial biofilm infections.
Preclinical animal models of oral squamous cell carcinoma (OSCC) have been extensively studied in recent years. Investigating the pathogenesis and potential therapeutic strategies of OSCC is required to further progress in this field, and a suitable research animal model that reflects the intricacies of cancer biology is crucial. Of the animal models established for the study of cancers, mouse tumor-bearing models are among the most popular and widely deployed for their high fertility, low cost, and molecular and physiological similarity to humans, as well as the ease of rearing experimental mice. Currently, the different methods of establishing OSCC mouse models can be divided into three categories: chemical carcinogen-induced, transplanted and genetically engineered mouse models. Each of these methods has unique advantages and limitations, and the appropriate application of these techniques in OSCC research deserves our attention. Therefore, this review comprehensively investigates and summarizes the tumorigenesis mechanisms, characteristics, establishment methods, and current applications of OSCC mouse models in published papers. The objective of this review is to provide foundations and considerations for choosing suitable model establishment methods to study the relevant pathogenesis, early diagnosis, and clinical treatment of OSCC.
Dendritic cell (DC)‐based cancer immunotherapy has exhibited remarkable clinical prospects because DCs play a central role in initiating and regulating adaptive immune responses. However, the application of traditional DC‐mediated immunotherapy is limited due to insufficient antigen delivery, inadequate antigen presentation, and high levels of immunosuppression. To address these challenges, engineered biomaterials have been exploited to enhance DC‐mediated immunotherapeutic effects. In this review, vital principal components that can enhance DC‐mediated immunotherapeutic effects are first introduced. The parameters considered in the rational design of biomaterials, including targeting modifications, size, shape, surface, and mechanical properties, which can affect biomaterial optimization of DC functions, are further summarized. Moreover, recent applications of various engineered biomaterials in the field of DC‐mediated immunotherapy are reviewed, including those serve as immune component delivery platforms, remodel the tumor microenvironment, and synergistically enhance the effects of other antitumor therapies. Overall, the present review comprehensively and systematically summarizes biomaterials related to the promotion of DC functions; and specifically focuses on the recent advances in biomaterial designs for DC activation to eradicate tumors. The challenges and opportunities of treatment strategies designed to amplify DCs via the application of biomaterials are discussed with the aim of inspiring the clinical translation of future DC‐mediated cancer immunotherapies.