Biomaterials Science最新文献

Oral health is essential to general health. The diagnosis of dental diseases and treatment planning of dental care need to be straightforward and accurate. Recent studies have reported the use of aptamers in dentistry to achieve a simple diagnosis and facilitate therapy. Aptamers comprise nucleic acid sequences that possess a strong affinity for their target. Synthesized chemically, aptamers have several advantages, including smaller size, higher stability, and lower immunogenicity compared with monoclonal antibodies. They can be used to detect biomarkers in saliva and the presence of various pathogens, or can be used as a targeted drug delivery system for disease treatment. This review highlights current research on aptamers for dental care, especially the recent progress in oral disease diagnosis and therapeutics. The challenges and unresolved problems faced by the clinical use of aptamers are also discussed. In the future, the clinical applications of aptamers will be further extended to include, for example, dental indications and regenerative dentistry.

Immune-mediated glomerular diseases lead to chronic kidney disease (CKD), primarily through mechanisms such as immune cell overactivation, mitochondrial dysfunction and imbalance of reactive oxygen species (ROS). We have developed an ultra-small nanodrug composed of Mn₃O₄ nanoparticles which is functionalized with biocompatible ligand citrate (C-Mn₃O₄ NPs) to maintain cellular redox balance in an animal model of oxidative injury. Furthermore, this ultra-small nanodrug, loaded with tacrolimus (Tac), regulated the activity of immune cells. We established a doxorubicin (DOX)-induced CKD model in SD rats using conditions of oxidative distress. The results demonstrate the ROS scavenging capability of Mn₃O₄ NPs, which mimics enzymatic activity, and the immunosuppressive effect of tacrolimus. This combination promotes targeted accumulation in the renal region with sustained drug release through the enhanced permeability and retention (EPR) effect. Tac@C-Mn₃O₄ protects the structural and functional integrity of mitochondria from oxidative damage while eliminating excess ROS to maintain cellular redox homeostasis, thereby suppressing the overexpression of pro-inflammatory cytokines to restore kidney function and preserve a normal kidney structure, reducing inflammation and regulating antioxidant stress pathways. This dual-pronged treatment strategy also provides novel strategies for CKD management and demonstrates substantial potential for clinical translational application.

The healing of complex diabetic wounds with a hyperglycemic microenvironment and bacterial infection is considered an important clinical issue. In this study, glucose oxidase (GOx) and gold nanoclusters (AuNCs) were encapsulated in quaternary carboxymethyl chitosan (QCMCS)/sodium alginate oxide (OSA) hydrogels and were immersed in tannic acid (TA) solution to achieve antioxidant, antibacterial, pro-angiogenesis, pro-collagen deposition and real-time monitoring functions. In vitro studies showed that TA-QCMCS/OSA@GOx@AuNC hydrogels had inhibition rates of 98.99% and 99.99% against S. aureus and E. coli, respectively, and the survival rate of mouse fibroblasts (L929) was over 95%. In vivo studies showed that TA-QCMCS/OSA@GOx@AuNC hydrogels were 97.28% effective in healing diabetic wounds. In addition, image signals from TA-QCMCS/OSA@GOx@AuNC hydrogels can be collected in real time to accurately obtain glucose concentration values of diabetic wounds and reflect the healing status of diabetic wounds in a timely manner. The results showed that TA-QCMCS/OSA@GOx@AuNC hydrogels provide a novel idea for real-time monitoring of diabetic wound treatment.

The intricate nature of the tumor microenvironment (TME) results in the inefficient delivery of anticancer drugs within tumor tissues, significantly compromising the therapeutic effect of cancer treatment. To address this issue, transdermal drug delivery microneedles (MNs) with high mechanical strength have emerged. Such MNs penetrate the skin barrier, enabling efficient drug delivery to tumor tissues. This approach enhances drug bioavailability, while also mitigating concerns such as liver and kidney toxicity associated with intravenous and oral drug administration. Notably, stimulus responsive MNs designed for drug delivery have the capacity to respond to various biological signals and pathological changes. This adaptability enables them to exert therapeutic effects within the TME, exploiting biochemical variations and tailoring treatment strategies to suit tumor characteristics. The present review surveys recent advancements in responsive MN systems. This comprehensive analysis serves as a valuable reference for the prospective application of smart MN drug delivery systems in cancer therapy.

DNA modification of the plasma membrane is an excellent approach for controlling membrane–protein interactions, modulating cell–cell/cell–biomolecule interactions, and extending the biosensing field. The hydrophobic insertion of DNA conjugated with hydrophobic anchoring molecules is utilized for tethering DNA on the cell membrane. In this study, we developed an alternative approach to tether DNA on the plasma membrane based on ssDNA- and cholesterol-binding proteins. We designed a fusion protein (Rep–ALOD4) composed of domain 4 of anthrolysin O (ALOD4), which binds to cholesterol in the plasma membrane, and a replication initiator protein derived from porcine circovirus type 2 (Rep), which forms covalent bonds with single-stranded DNA (ssDNA) with a Rep recognition sequence. Rep–ALOD4 conjugates ssDNA to Rep and binds to the plasma membrane via cholesterol, thus tethering ssDNA to the cells. Quartz crystal microbalance measurements showed that membrane cholesterol binding of Rep–ALOD4 to the lipid bilayer containing cholesterol was accelerated above 20% (w/w) cholesterol in the lipid bilayer. Rep–ALOD4 was conjugated to fluorescein-labeled ssDNA (S-FITC–Rep–ALOD4) and used to treat human cervical tumor HeLa cells. The green signal assigned to S-FITC–Rep–ALOD4 was detected along HeLa cells, whereas diminished by cholesterol removal with methyl β-cyclodextrins. Moreover, ssDNA-conjugated Rep–ALOD4 tethered ssDNA-conjugated functional proteins on the HeLa cell plasma membrane via complementary base pairing. Collectively, Rep–ALOD4 has the potential as an ssDNA-tethering material via plasma membrane cholesterol to extend cell surface engineering.

Precise control of cellular temperature at the microscale is crucial for developing novel neurostimulation techniques. Here, the effect of local heat on the electrophysiological properties of primary neuronal cultures and HEK293 cells at the subcellular level using a cutting-edge micrometer-scale thermal probe, the diamond heater-thermometer (DHT), is studied. A new mode of local heat action on a living cell, thermal-capture mode (TCM), is discovered using the DHT probe. In TCM, the application of a 50 °C temperature step induces a great increase in cellular response, allowing the cell to be thermally captured and depolarized by up to 20 mV. This thermal effect is attributed to local phase changes in the phospholipid membrane, enabling precise and reproducible modulation of cell activity. The TCM is shown to open up new opportunities for thermal cell stimulation. DHT reliably triggers action potentials (APs) in neurons at rates up to 30 Hz, demonstrating the ability to control cell excitability with millisecond and sub-millisecond resolution. AP shape is modulated by local heat as well. The ability to precisely control the AP shape and rate via thermal-capture mode opens new avenues for non-invasive, localized neurostimulation techniques, particularly in controlling neuron excitability.

Advances in nanotechnology offer promising strategies to overcome the limitations of single-drug therapies in hepatocellular carcinoma (HCC) and other cancers such as multidrug resistance and variable drug tolerances. This study proposes a targeted nanoparticle system based on a poly(β-aminoester) (PβAE) core and a hyaluronic acid (HA) shell, designed for the codelivery of doxorubicin (DOX) and indocyanine green (ICG) to effectively treat HCC. These nanoparticles demonstrated remarkable physicochemical and colloidal stability, pH- and temperature-responsive release, enhanced cellular uptake, and drug retention within tumors. Upon near-infrared (NIR) irradiation, the photothermal conversion of ICG elevated local tumor temperatures up to 53.6 °C, enhancing apoptotic cell death significantly compared to chemotherapy alone (p < 0.05). Furthermore, the dual delivery system significantly enhanced therapeutic efficacy, as evidenced by a marked decrease in tumor growth in vivo compared to controls (p < 0.01). These findings illustrate that the HA/PβAE/DOX/ICG nanoparticles are not only able to precisely target tumor cells but also overcome the limitations associated with traditional chemotherapies and photothermal treatments, suggesting a promising avenue for clinical translation of cancer therapy.

Otitis media is a prevalent pediatric condition. Local delivery of antimicrobial agents to treat otitis media is hindered by the low permeability of the stratum corneum layer in the tympanic membrane. While nanozymes, often inorganic nanoparticles, have been developed to cure otitis media in an antibiotic-free manner in a chinchilla animal model, the tympanic membrane creates an impenetrable barrier that prevents the local and non-invasive delivery of nanozymes. Here, we use a newly developed vanadium pentoxide (V₂O₅) nanowire as an example, which catalyzes the metabolic products of an otitis media pathogen (Streptococcus pneumoniae) into antiseptics, to explore the transtympanic delivery strategies for antimicrobial nanozymes. V₂O₅ nanowires with smaller dimensions (<300 nm in length) were synthesized by optimizing the synthesis conditions. To enhance penetrations across intact tympanic membranes, the nanowire was mixed or surface-modified with a trans-tympanic peptide, TMT3. The peptide-modified nanowires were characterized for their physical properties, catalytic activities, and antimicrobial activities. The cytotoxicity profile and permeation across ex vivo tympanic membrane samples were analyzed for the mixed and surface-modified nanozyme formulations.

The development of safe and efficient hemostatic materials is medically important to prevent death due to trauma bleeding. Exploiting the synergistic effect between the D-periodic functional domain of collagen fibrils on platelet activation and cationic chitosan on erythrocyte aggregation is expected to develop performance-enhanced hemostatic materials. In this study, we prepared collagen fibrils and chitosan composite hemostatic materials by modulating the self-assembled bionic fibrillation of collagen with different degrees of deacetylation (DD, 50%, 70% and 85%) of chitosan. The findings indicated that chitosan promoted collagen self-assembly, with all the collagen fibrils demonstrating a typical D-periodical structure similar to that of the native collagen. Furthermore, the composite demonstrated enhanced structural integrity and procoagulant capacity along with good biocompatibility. Notably, the fibrillar composites with 70% DD of chitosan exhibited optimal mechanical properties, procoagulant activity, and adhesion of erythrocytes and platelets. Compared to pure collagen fibrils and the commercial hemostatic agent Celox™, the collagen/chitosan fibrillar composite treatment significantly accelerated hemostasis in the rat tail amputation model and liver injury model. This research offers new insights into the development of hemostatic materials and indicates that collagen-chitosan composites hold promising potential for clinical applications.

Nanotechnology has shown great promise for researchers to develop efficient nanocarriers for better therapy, imaging, and sustained release of drugs. The existing treatments are accompanied by serious toxicity limitations, leading to severe side effects, multiple drug resistance, and off-target activity. In this regard, nanogels have garnered significant attention for their multi-functional role combining advanced therapeutics with imaging in a single platform. Nanogels can be functionalized to target specific tissues which can improve the efficiency of drug delivery and other challenges associated with the existing nanocarriers. Translation of nanogel technology requires more exploration towards stability and enhanced efficiency. In this review, we present the advances and challenges related to nanogels for cancer therapy, ophthalmology, neurological disorders, tuberculosis, wound healing, and anti-viral applications. A perspective on recent research trends of nanogels for translation to clinics is also discussed.