ACS Applied Bio Materials最新文献

Recently, nitric oxide (NO) has been shown to induce immunogenic cell death (ICD) in tumor cells through endoplasmic reticulum (ER) stress and mitochondrial outer membrane permeabilization (MOMP). However, NO is unstable, making direct delivery difficult. In this study, we developed a cell-penetrating polypeptide-based NO donor, poly(l-guanidine) (PLG). Given that the guanidine structure can be catalyzed by reactive oxygen species (ROS) to produce NO, helical PLG plays three roles: spontaneous cell penetration, intracellular ROS generation to produce NO, and induction of ICD. The results revealed that helical PLG generates NO inside the cell by self-inducible guanidine oxidation and that NO effectively elicits ICD by ER stress- and MOMP-dependent intertwined mechanisms.

Cell-based immunotherapies have emerged as promising cancer treatment modalities, demonstrating remarkable clinical efficacy. As interest in applying immune cell-based therapies to solid tumors has gained momentum, experimental models that enable long-term monitoring and mimic clinical administration are increasingly necessary. This study explores the potential of scaffold-based cell culture technologies, specifically three-dimensional (3D) extracellular matrix (ECM)-like frameworks, as promising solutions. These frameworks facilitate unhindered immune cell growth and enable continuous cancer cell culture. The three-dimensional (3D) cell culture model was developed using tailored scaffolds for natural killer (NK) cell culture. Within this framework, A549 lung cancer cells were cocultured with NK cells, allowing real-time monitoring for up to 28 days. The expression of critical markers associated with anticancer drug resistance and epithelial-mesenchymal transition (EMT) was evaluated in cancer cells within this 3D culture context. Compared to conventional 2D monolayer cultures, this 3D scaffold-based culture revealed that solid tumor cells, specifically A549 cells, exhibited heightened resistance to anticancer drugs. Additionally, the 3D culture environment upregulated the expression of EMT markers namely vimentin, N-cadherin, and fibronectin, while NK and zEGFR-CAR-NK cells displayed anticancer effects. In the two-dimensional (2D) coculture, only zEGFR-CAR-NK cells exhibited such effects in the 3D coculture system, highlighting an intriguing inconsistency with the 2D culture model, further confirmed by in vivo experiments. This in vitro 3D cell culture model reliably predicts outcomes in NK immunotherapy experiments. Thus, it represents a valuable tool for investigating drug resistance mechanisms and assessing the efficacy of immune cell-based therapies. By bridging the gap between in vitro and in vivo investigations, this model effectively translates potential treatments into animal models and facilitates rigorous preclinical evaluations.

Atherosclerosis, characterized by chronic inflammation within the arterial wall, remains a pivotal concern in cardiovascular health. We developed a dual-targeted liposomal system encapsulating Dll4-targeting siRNA, designed to selectively bind to pro-inflammatory M1 macrophages through surface conjugation with anti-F4/80 and anti-CD68 antibodies. The Dll4-targeting siRNA is then delivered to the macrophages, where it silences Dll4 expression, inhibiting Notch signaling and reducing plaque vulnerability. Emphasizing accuracy in targeting, the system demonstrates effective suppression of Dll4, a key modulator of atherosclerotic progression, and vulnerability via VSMCs phenotypic conversion and senescence. By employing liposomes for siRNA delivery, we observed enhanced stability and specificity of the siRNA. Alongside the therapeutic efficacy, our study also evaluated the safety profile and pharmacokinetics of the dual-targeted liposomal system, revealing favorable outcomes with minimal off-target effects and optimal biodistribution. The integration of RNA interference techniques with advanced nanotechnological methodologies signifies the importance of targeted delivery in this therapeutic approach. Preliminary findings suggest a potential attenuation in plaque development and vulnerability, indicating the therapeutic promise of this approach. This research emphasizes the potential of nanocarrier-mediated precision targeting combined with a reassuring safety and pharmacokinetic profile for advancing atherosclerosis therapeutic strategies.

This study demonstrates the synthesis of 1D surface vertically aligned nanorods of ZnO on the fluorine-doped tin oxide-coated glass substrate (ZnO-VANRs/FTOs) synthesized via a chemical route for the targeted electrochemical sensing of aniline. The ZnO-VANRs/FTOs were 1.57 ± 0.03 μm in length with excellent crystallinity and high density (1.52 × 10¹³ rod no./m²). ZnO-VANRs formation increased surface roughness by 2.4- and 4.7-fold compared to the bare FTOs and seeded FTOs (ZnO-seed/FTOs), respectively. The ZnO-VANRs/FTOs electrodes could increase the effective surface area from 0.154 to 0.384 cm² with about 86.85% reduction in charge transfer resistance compared to the bare FTOs. The peak current response (at 0.281 V vs Ag/AgCl) of aniline deposition was boosted by 81.52% with the rise in temperature from 15 to 45 °C. The reduction of aniline at ZnO-VANRs/FTOs involved a reversible two-electron diffusion control process with a heterogeneous reaction rate constant (k⁰) of 1.82 s^-1 and a formal potential (E⁰) of 0.289 V vs Ag/AgCl. The ZnO-VANRs/FTOs electrode showed limits of detection of 0.193 μM (sensitivity 0.198 μA·μM^-1·cm^-2) and 0.588 μM (sensitivity of 0.065 μA·μM^-1·cm^-2) between the working ranges of 0-20 and 20-160 μM, respectively. The fabricated sensor was unprecedently selective toward aniline sensing, and p-nitroaniline, chlorobenzene, chlorpyrifos, Cu²⁺, Pb²⁺, Ni²⁺, Cd²⁺, albumin bovine, Escherichia coli, and ciprofloxacin could not interfere with aniline sensing and its sensitivity. However, the peak current was marginally decayed by 2.63% up to the 6th cycle. Moreover, ZnO-VANRs/FTOs catalyzed the sensing of aniline spiked in the environmental matrices, conforming well to liquid chromatography.

Bacterial infections significantly deteriorate the process of wound healing. The wound dressings loaded with antimicrobials are widely used to reduce bacterial infections. However, release-based sterilization may increase the risk of drug resistance of bacteria and complicate translation. Thus, the development of long-term intrinsic antibacterial wound dressings is highly desirable. In this study, an intrinsic antibacterial hydrogel (PVA/PPG-HBPL) consisting of poly(vinyl alcohol) (PVA), poly(polyethylene glycol methyl ether methacrylate-co-glycidyl methacrylate) (PPG), and hyperbranched poly-l-lysine (HBPL) was designed and fabricated. The mechanical properties of the PVA/PPG-HBPL hydrogel were enhanced by hydrogen bonding and semi-interpenetrating networks. It also possessed a favorable ability to absorb the wound exudates. The release of antibacterial HBPL was significantly decreased by the methods of cyclic freeze-thawing and covalent cross-linking during hydrogel fabrication, enabling the PVA/PPG-HBPL hydrogel with intrinsic and long-term antibacterial performance. The PVA/PPG-HBPL hydrogel dressing killed 99.9% of methicillin-resistant Staphylococcus aureus (MRSA) cultured on its surface without observable cytotoxicity in vitro. It observably shortened the healing process by 2 orders of magnitude of MRSA colonies compared with the control in the MRSA-infected full-thickness skin wound of rats in vivo even after being soaked in phosphate-buffered saline (PBS) for 21 days (PBS was changed every 3 days). The antibacterial hydrogels could kill wound bacteria in a timely manner, significantly reduce inflammatory cell infiltration, and promote neovascularization and collagen deposition.

Synthetic hyperbranched polyesters with potential therapeutic properties were synthesized using the bifunctional polyethylene glycol or PEG with different molecular weights, ca., 4000, 6000, and 20,000 g/mol, and the trifunctional trans-aconitic acid or TAA. During polycondensation, a fixed amount of PEG was allowed to react with varying amounts of TAA (1:1 and 1:3) to control the branching extents. It was found that the synthetic polyesters had a considerable yield and were highly water soluble. Spectroscopic data (Fourier transform infrared and ¹H NMR) confirmed the polyester formation; the branching percentages were determined from ¹H NMR spectroscopy which varied from 73% to 22% among the synthesized samples. As the molecular weight of PEG was increased, the branching percentage drastically dropped. All polyesters were found to be negatively charged due to the ionization of unreacted -COOH in the branched ends at the working pH (7.4). Both the hydrodynamic size and intrinsic viscosity were found to reduce as the branching extent increased. Among the sets of polyesters, the one with the highest branching percentage (73%) showed the core-shell morphology (evident from field emission scanning electron microscopy and transmission electron microscopy studies). It also exhibited the highest efficiency toward Ca²⁺ influx in neuronal cells due to the unique morphology and the negatively charged surface. Nevertheless, this particular grade of polyester along with all the other grades was cytocompatible and induced reactive oxygen species generation. Since the maximally branched grade was highly efficient in altering the Ca²⁺ signaling through stronger influx, it may well be tested for treating neuronal disorders in vivo in future.

Leather is a product that has been used for millennia. While it is a natural material, its production raises serious environmental and ethical concerns. To mitigate those, the engineering of sustainable biobased leather substitutes has become a trend over the past few years. Among the biobased materials, mycelium, the fungal "root" of a mushroom, is one of the promising alternatives to animal leather, as a material with tunable physicomechanical properties. Understanding the effect of humidity on mycelium-based leather material properties is essential to the production of durable, competitive, and sustainable leather products. To this end, we measured the water sorption isotherms on several samples of mycelium-based leather materials and investigated the effects of water sorption on their elastic properties. The ultrasonic pulse transmission method was used to measure the wave speed through the materials while measuring their sorption isotherms at different humidity levels. Additionally, the material's properties were mechanically tested by performing uniaxial tensile tests under ambient and immersed conditions. An overall reduction in elastic moduli was observed during both absorption and immersion. The changes in the measured longitudinal modulus during water sorption reveal changes in the elasticity of the test materials. The observed irreversible variation of the longitudinal modulus during the initial water sorption can be related to the material production process and the presence of various additives that affect the mechanical properties of the leather materials. Our results presented here should be of interest to material science experts developing a new generation of sustainable leather products.

Expanded polytetrafluoroethylene (ePTFE) failed to achieve clinical application in the field of small-diameter blood vessels due to its lack of elasticity in the circumferential direction and high stiffness. Excellent multidirectional elasticity and dynamic compliance matching with natural blood vessels are important means to solve the problem of acute thrombosis and poor long-term patency. Herein, novel PTFE spinning blood vessels were prepared by the PTFE emulsion electrospinning process, which not only presented good bidirectional elasticity but also promoted the adhesion and proliferation of endothelial cells and induced the contractile expression of SMCs. And, a PTFE-shish and aminated polycaprolactone (PCL)-kebab structure has been developed that converted the chemically inert PTFE surface into a drug-loading platform for the multifunctionalization of PTFE vascular grafts. It provides novel preparation methods for the application of new bidirectional elastic small-diameter artificial blood vessels and their surface functionalization construction.

For better bone regeneration, precise control over the architecture of the scaffolds is necessary. Because the shape of the pore may affect the bone regeneration, therefore, additive manufacturing has been used in this study to fabricate magnetic bioactive glass (MBG) scaffolds with three different architectures, namely, grid, gyroid, and Schwarz D surface with 15 × 15 × 15 mm³ dimensions and 70% porosity. These scaffolds have been fabricated using an in-house-developed material-extrusion-based additive manufacturing system. The composition of bioactive glass was selected as 45% SiO₂, 20% Na₂O, 23% CaO, 6% P₂O₅, 2.5% B₂O₃, 1% ZnO, 2% MgO, and 0.5% CaF₂ (wt %), and additionally 0.4 wt % of iron carbide nanoparticles were incorporated. Afterward, MBG powder was mixed with a 25% (w/v) Pluronic F-127 solution to prepare a slurry for fabricating scaffolds at 23% relative humidity. The morphological characterization using microcomputed tomography revealed the appropriate pore size distribution and interconnectivity of the scaffolds. The compressive strengths of the fabricated grid, gyroid, and Schwarz D scaffolds were found to be 14.01 ± 1.01, 10.78 ± 1.5, and 12.57 ± 1.2 MPa, respectively. The in vitro study was done by immersing the MBG scaffolds in simulated body fluid for 1, 3, 7, and 14 days. Darcy's law, which describes the flow through porous media, was used to evaluate the permeability of the scaffolds. Furthermore, an anticancer drug (Mitomycin C) was loaded onto these scaffolds, wherein these scaffolds depicted good release behavior. Overall, gyroid-structured scaffolds were found to be the most suitable among the three scaffolds considered in this study for bone tissue engineering and drug-delivery applications.

Bacterial infections impede wound healing and pose significant challenges in clinical care. There is an immediate need for safe and targeted antivirulence agents to fight bacterial infections effectively. In this regard, bioderived nanovesicles have shown significant promise. This work demonstrated significant antibacterial properties of extracellular nanovesicles derived from plant (mint) leaf juice (MENV). A hydrogel (HG) was developed using oxidized alginate and chitosan and loaded with antibacterial MENVs (MENV-HG). This formulation was investigated for topical HG dressings to treat Gram-positive Micrococcus luteus and Gram-negative Escherichia coli-invasive wounds. The developed HG was injectable, biocompatible (>95% cell was viable), nonhemolytic (<5% hemolytic capacity), self-healing and exhibited strong physical and mechanical interactions with the bacteria cells (MENV-HG-treated bacteria were significantly more elastic compared to the control in both M. luteus (1.01 ± 0.3 MPa, p < 0.005 vs 5.03 ± 2.6) and E. coli (5.81 ± 2.1 MPa vs 10.81 ± 3.8, p < 0.005). MENV-HG was topically applied on wounds with a slow MENV release profile, ensuring effective healing. These in vivo results demonstrated decreased inflammation and expedited healing within 10 days of treatment (wound area closure was 99% with MENV-HG treatment and 87% for control). Taken together, MENV-HGs have the potential for a scalable and sustainable wound dressing strategy that works satisfactorily for bacteria-infected wound healing and to be validated in clinical trials.