Journal of materials chemistry. B最新文献

Acne is a common chronic inflammatory skin disease associated with Cutibacterium acnes (C. acnes). Although photodynamic therapy (PDT) effectively improves acne, the transdermal delivery of photosensitizers and limited light penetration through the skin restrict its therapeutic efficacy. In this study, we developed a dual-functional flexible microneedle patch using 3D printing technology, capable of simultaneously delivering the photosensitizer 5-aminolevulinic acid (ALA) and blue light. The microneedle patch exhibits favorable mechanical properties (a fracture force of 2.47 N per patch and a drug loading capacity of 655 ± 0 µg per patch) and increases the light penetration depth in tissue by 128.6%. The combination of the microneedle patch and blue light achieved an antibacterial rate of 97.10 ± 1.1% against C. acnes in vitro. In animal experiments, this strategy resulted in significantly smaller acne lesions by day 7 (size: 1.53 ± 0.30 mm; thickness score: 0.20 ± 0.45; n = 5 per group, P < 0.05), with no significant adverse effects observed during the experimental period. Our preclinical findings demonstrate that this dual-function microneedle patch provides proof-of-concept for its future development as a novel integrated platform for PDT.

The reconstruction of critical-size skull defects is challenged by the limited availability of autologous bone grafts and the mismatch between degradation rate and new bone formation in synthetic scaffolds. Wollastonite (CaSiO₃; CSi), despite its favorable bioactivity, suffers from rapid degradation and inadequate structural stability, hindering its clinical application. In this study, we conducted systematic parameter optimization by fabricating a series of 3D-printed wollastonite scaffolds with uniform phosphate-doping levels (CSi-Px, where x = 0, 3, 6, and 9 mol%) via digital light processing (DLP). Our objective was to identify the optimal doping concentration that best balances the scaffold's degradation behavior with its osteogenic capacity. The scaffolds were characterized in terms of pore structure, compressive strength, in vitro degradation and re-mineralization capacity. Cell proliferation and osteogenic differentiation experiments were conducted using bone marrow mesenchymal stem cells (BMSCs). In particular, the bone regeneration efficacy was evaluated in a rabbit cranial defect model over a 12-week period. The results indicated that phosphate doping significantly promoted the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), enhanced the mineralization capacity of the scaffold, reduced the in vivo degradation rate of the calcium silicate scaffold, and maintained its structural and morphological stability, thereby providing improved osteoconductive capability. The phosphate content significantly influences bone repair outcomes by modulating the degradation behavior and bioactivity of CSi, and 6% phosphate doping is identified as the optimal content, which may balance the structural stability, biodegradation rate, and potent osteogenic capacity. This study provides quantitative design guidelines for developing calcium-silicon-phosphorus (Ca-Si-P)-based bioceramics.

Gd-based contrast agents (GBCAs) with high relaxivity and favorable in vivo profiles are greatly desired yet present formidable challenges, especially on the molecular side. Here, we report a macrocyclic GBCA (namely Gd-IN-DO3A) characterized by the presence of an isonicotinate group (IN) tethered asymmetrically to the macrocyclic DO3A scaffold with the pyridine-N coordinated to the Gd³⁺ center. Our studies reveal that it shows an assembly-dissociable feature with human serum albumin (HSA) by moderate non-covalent interactions at Sudlow site II, showing a binding fraction of ∼50%, a binding constant (K_a) of 316 M^-1 and a dissociation constant (K_D) of 5.24 µM. This dynamic GBCA-HSA adduct ensures a high r₁ relaxivity of ∼23.75 mM^-1 s^-1 in 4.5% HSA (∼8.29 mM^-1 s^-1 in water) and enables favorable pharmacokinetic properties, with a blood half-life (t_1/2) of ∼3.2 h, desirable biodistribution and excretion, and superior lesion imaging performance. These results suggest that developing novel GBCAs bearing an assembly-dissociable feature with albumin via moderate non-covalent interactions could serve as a compensation approach for enhanced magnetic resonance imaging and in vivo profiles.

Osteogenic cell sheets retain intercellular junctions and their native extracellular matrix, enabling stage-specific support for bone repair. To engineer such sheets under controlled mechanical cues, we developed stiffness-tuned composite hydrogels via enzymatic crosslinking of phenolated hyaluronic acid (HA-Ph) and gelatin (Gelatin-Ph) using horseradish peroxidase and hydrogen peroxide (H₂O₂). We evaluated the ability of these hydrogels to support osteogenic differentiation and enable cell sheet fabrication from human bone marrow-derived mesenchymal stem cells (bMSCs). Hydrogel stiffness was controlled by varying the degree of phenolation in HA-Ph (3.7, 4.3, and 5.2 phenol groups per 100 repeating units) at a fixed polymer concentration, resulting in hydrogels with Young's moduli of 3.3, 6.0, and 10.1 kPa, respectively. The stiffest hydrogel (10.1 kPa) enhanced YAP nuclear localisation in bMSCs, whereas the hydrogel with intermediate stiffness (6.0 kPa) most effectively induced osteogenic differentiation, as evidenced by the high expression levels of osteogenic marker genes, including ALP1, COL1A1, and RUNX2. By day 7, cells on the hydrogels had already initiated differentiation, enabling the detachment of cell sheets containing partially differentiated bMSCs, which were subsequently re-adhered to a new surface without losing their osteogenic potential. These findings demonstrate the potential of stiffness-tuned HA-Ph/Gelatin-Ph composite hydrogels as effective platforms for bone tissue engineering using cell sheets.

The invasive nature of brain implants remains a major limitation in neuromodulation strategies, often leading to chronic inflammation. To address this, soft coatings are applied on rigid probes to reduce the mechanical mismatch at the interface, or flexible probes are implemented accompanied by temporary stiffeners. This study presents a hybrid strategy integrating both approaches by applying a permanent hydrogel coating onto flexible neural probes. Moreover, we utilise the applied coatings as tool for post-operative non-invasive imaging via functionalisation of the hydrogel with 5-acrylamido-2,4,6-triiodoisophthalic acid (AATIPA), a monomer that increases radiodensity. Rheological measurements confirmed that AATIPA incorporation did not significantly alter the hydrogels' mechanical properties (storage moduli ranging from 139 ± 33.5 to 186 ± 55.5 kPa). Subsequently, we show that coated flexible probes exhibited a two-fold increase in critical buckling force compared to uncoated counterparts, indicating improved mechanical robustness evidenced through enhanced insertion performance in agarose brain phantoms. The mechanical contrast supports the dual purpose of the material in our application: the coatings provide stiffness to facilitate probe insertion in the dry state, while transitioning to a compliant, soft interface upon swelling, post-implantation. Finally, the radiodense coating enabled successful visualization of the probes in the hippocampus of a mouse model using μ-CT imaging. This approach offers a promising route for improving the mechanical and imaging performance of neural implants, potentially reducing reliance on post-mortem histology and enhancing real-time feedback in neuromodulation research.

Dental caries, one of the most prevalent oral diseases among adults and children, is caused by oral microorganisms and diet and involves a complex, multi-step process of biofilm formation and tooth decay. The existing clinical treatment modalities are not satisfactory due to the disadvantages of incomplete eradication of pathogens, poor material compatibility and susceptibility to secondary caries. In recent years, there has been a growing interest in treating dental caries, with various strategies emerging to combat these bacterial films and promote tooth remineralization. However, comprehensive reviews on this topic are still relatively scarce. Therefore, this review first summarizes two primary aspects of treating dental caries, namely, the antibacterial and mineralization strategies in oral environments, and then discusses the synergistic effect of biofilm removal and in situ tissue remineralization, emphasizing the critical role of a combined approach for efficient treatment. This review offers novel insights and directions for dental caries treatment and provides reference for the design of oral biomedical materials.

The COVID-19 pandemic caused by SARS-CoV-2 underscored the global need for rapid, efficient drug discovery platforms to combat emerging viral threats. Conventional antiviral screening methods are often time-consuming and low-throughput, making them insufficient for timely therapeutic development during acute outbreaks. RNA-dependent RNA polymerase (RdRp), a key enzyme in viral replication, represents a validated antiviral target for RNA viruses, including SARS-CoV-2. However, few assays directly monitor RdRp activity in a high-throughput format. To address this gap, we developed a fluorescence-based assay for real-time monitoring of RdRp activity using graphene oxide nanomaterials. Here, we designed a graphene oxide-based RdRp assay that transduces polymerase activity into measurable fluorescence intensity changes. The assay is rapid, homogeneous, and compatible with multi-well plate formats for high-throughput screening. Using this platform, we screened a library of FDA-approved small molecules and identified fingolimod, an immunomodulatory drug for multiple sclerosis, as a potential RdRp inhibitor. In vitro cell-based assays confirmed that fingolimod significantly reduced SARS-CoV-2 replication without cytotoxicity at therapeutic concentrations. This result supports fingolimod's potential as a repurposed direct-acting antiviral agent. The assay's robustness highlights its applicability in antiviral drug discovery, enabling rapid responses to future viral outbreaks. This graphene oxide-based RdRp assay provides a versatile tool for antiviral screening and demonstrates the feasibility of repurposing approved drugs as direct-acting antivirals. The platform's adaptability and rapid readout capability make it well-suited for pandemic preparedness and therapeutic discovery against emerging viral threats.

Tongue injuries are among the most common acute soft tissue injuries encountered in oral clinical practice. Suturing, as the conventional treatment, often leads to tissue distortion and tension-induced collagen over-deposition, resulting in scarring and restricted tongue mobility. Sutures are also prone to microbial accumulation and provoke inflammation as foreign bodies. In this study, a hydrogel patch specifically designed for the tongue's moist, frequently moving, and richly vascularized environment was developed for better healing of tongue injuries. Briefly, a chitosan-polyacrylic acid-tannic acid hydrogel matrix is loaded with Cu-MOF to form a CPTCu hydrogel, ensuring stable binding and controlled release of copper, while maintaining mechanical compliance with tongue tissue for continuous protection. The CPTCu hydrogel exhibited excellent biocompatibility, achieving a free radical scavenging rate of 73.6% and a bactericidal rate of over 99%. Compared with suturing, the CPTCu hydrogel significantly reduced the collagen volume by 35.9% and enhanced angiogenesis by 103.2%, and also effectively promoted regeneration of local muscle fibers in a rat tongue wound model. These results demonstrate that the CPTCu hydrogel is a promising candidate for optimized scarless tongue healing.

Dopamine (DA) is a key neurotransmitter required for attention, learning, movement, emotion, and cognition. Imbalance in DA levels is linked to disorders such as depression, addiction, schizophrenia, and neurodegenerative diseases. Therefore, a simple, sensitive, and selective method for DA detection is required. In this study, carbon and nitrogen co-doped zinc sulfide (ZnS@N/C) nanodots combined with multi-walled carbon nanotubes (MWCNT) were developed for DA detection in PC-12 live cells. The ZnS@N/C nanodots were synthesized from a leaf-like zeolite imidazolate framework (ZIF-L), carboxymethyl cellulose (CMC), and sodium diethyldithiocarbamate trihydrate (DEDTC) via thermal annealing. DEDTC acted as a sulfur source, while CMC acted as a carbon source and improved the dispersibility of the MWCNT in the composite. Electrochemical properties were confirmed using cyclic voltammetry, electrochemical impedance spectroscopy, and amperometry (i-t). The ZnS@N/C/MWCNT composite exhibited excellent electrochemical performance due to the synergistic effects of ZnS@N/C (which provided high electrocatalytic activity and more active sites) and MWCNT (which enhanced conductivity). Amperometry (i-t) revealed that the ZnS@N/C/MWCNT/screen-printed electrode (SPCE) showed good linearity in the DA concentration range of 0.0125-1774 µM, with a low detection limit of 3.97 nM. Furthermore, the ZnS@N/C/MWCNT/SPCE successfully monitored the DA levels in PC-12 cells under K⁺ stimulation in a neurological environment. These results demonstrated that the ZnS@N/C/MWCNT/SPCE is an efficient, selective, and sensitive sensor for rapid DA detection, offering potential applications in biomedical research.

Transplantation of encapsulated islet cells can restore the normal physiological glycemic level in type-1 diabetic patients. However, the clinical rate of success of islet transplantation is limited by robust immune response, inadequate insulin release, and acute hypoxic stress. The physico-biochemical properties of an encapsulating hydrogel play an important role in successful islet transplantation, mitigating the challenges. Herein, we report a comprehensive screening of 20 different commonly available natural polymers based on their various physico-biochemical properties, ease of islet delivery (MIN6), and biological functioning. From the initial screening, the top four leads (alginate, pectin, agarose, and cellulose) were selected based on their long-term degradation, mechanical stability, and insulin release kinetics. Based on further in vitro assessment, pectin was identified as the lead polymer for the in vivo diabetes treatment study. Subcutaneous implantation of MIN6 (mouse beta pancreatic islet) encapsulated pectin hydrogel capsules restored and maintained normoglycemia for 60 days in both C57BL/6 (allogeneic) mice and Wistar rats (xenogeneic) in a streptozotocin-induced diabetic model, without the requirement of any external immunosuppressant. Furthermore, when pectin was used for encapsulation and delivery of isolated primary rat islets to diabetic C57BL/6 mice, it also restored normoglycemia within 3 days of transplantation in the xenogeneic setup and sustained it for 30 days. This study successfully identified a novel natural polymer, pectin, demonstrating potential for maintaining long-term islet viability in vivo and acting as an independent, promising platform for islet delivery in the management of type-1 diabetes.