ACS Applied Bio Materials最新文献

The development of multifunctional hemostatic agents from earth-abundant natural silicon-based minerals represents a sustainable strategy for biomedical applications. However, a key physicochemical challenge lies in their inherent phase complexity and structural heterogeneity, which hinder predictable integration of biofunctionality. In this work, we present an inorganic–organic interfacial engineering approach to fabricate a high-performance hemostat based on phytoliths. By leveraging synergistic noncovalent interactions with functional organic molecules, such as poly(acrylic acid) (PAA), polyethylenimine (PEI), polylysine (EPL), and berberine (BER), we successfully incorporated hemostatic, antibacterial, and antioxidant properties into a unified platform. The resulting multifunctional hemostat demonstrates excellent biocompatibility, rapid blood-triggered powder-to-hydrogel transition, and outstanding water absorption capacity. In a mouse liver hemorrhage model, the engineered phytolith-based hemostat achieved a remarkably short hemostasis time of 54.83 ± 4.06 s and minimal blood loss of only 107.97 ± 5.19 mg, significantly outperforming unmodified phytoliths and rivaling a commercial zeolite-based control. This work establishes a physicochemical rationale for repurposing natural mineral resources toward advanced multifunctional hemostatic applications.

Uncontrolled hemorrhage and wound infection are leading causes of preventable death in prehospital trauma care. Everyday garments, often used as improvised bandages, provide only passive compression without intrinsic bioactivity. Here, we report a low-cost cotton fabric engineered to split into bandages with rapid hemostatic and antibacterial functions. Citric-acid treatment introduces abundant carboxyl groups onto cotton fibers, enabling dense in situ growth of zeolitic imidazolate framework-8 (ZIF-8) loaded with tranexamic acid (TA). A predesigned tear zone balances high tensile strength (>681.39 N) for daily wear with low tear force (<6.75 N) for instant bandage formation. Upon exposure to wound-like exudate, the hybrid coating undergoes phosphate–protein cotriggered degradation, releasing Zn²⁺ and TA: Zn²⁺ disrupts bacterial membranes and catalyzes ROS generation, while TA stabilizes fibrin networks and inhibits fibrinolysis. This synergy achieves >99% suppression of Escherichia. coli and Staphylococcus aureus, a blood clotting index of 24.6%, a coagulation time of 230 s, and a 37.9% reduction in blood loss in a rat tail-amputation model compared with controls. By integrating green chemistry, MOF-enabled bioactivity, and mechanically encoded tearing, this work converts everyday clothing into ready-to-use, life-saving textiles for fast antibacterial protection and rapid hemostasis in prehospital emergencies.

The present study investigates the antibreast cancer potential of silver nanoparticles derived from the fungal endophyte Penicillium oxalicum (POAgNPs) using both in vitro and in vivo models. High-content analysis (HCA) demonstrated that POAgNPs significantly altered cellular and nuclear morphology, and we noted reduced cell impedance in human breast cancer cells MDA-MB-231 and MCF-7, indicating potent cytotoxicity. POAgNPs induced cell cycle arrest in the sub-G1 phase and promoted reactive oxygen species (ROS) generation, suggesting ROS-mediated apoptosis. Release studies confirmed efficient POAgNPs release at acidic pH (5.5), mimicking the tumor microenvironment, while the cellular uptake assay showed dose-dependent cytotoxicity. Moreover, POAgNPs exhibited antiangiogenic activity in the chick chorioallantoic membrane assay, indicating their potential to inhibit tumor neovascularization. In vivo, POAgNPs treatment mitigated the carcinogenic effects of 7,12-dimethylbenz[a]anthracene (DMBA) in breast tumor-bearing rats, as demonstrated by improved mammary tissue histology and significant restoration of oxygen saturation, total hemoglobin concentration, and reduced tumor vascularity measured via photoacoustic imaging (PAI). Biochemical assays revealed that POAgNPs helped restore the metabolic balance and oxidative status. Gene expression analysis showed upregulation of pro-apoptotic markers (CASPASE 8 and P53) and downregulation of antiapoptotic BCL-2 and the glucose transporter gene SLC2A1. Increased Caspase-3 activity further confirmed apoptosis induction. Collectively, these findings highlight the promise of POAgNPs as an effective antibreast cancer agent, warranting further research toward their development as a targeted nanotherapeutic.

Poly(ethylene glycol) (PEG) is widely used as a stealth polymer to enhance drug stability and circulation by reducing immune recognition. However, anti-PEG antibodies are increasingly reported in humans, leading to accelerated drug clearance and adverse immune responses. While ensemble assays have clarified the scheme of PEG–antibody binding, they lack the resolution to probe molecular-scale mechanics. Here, we used atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS) to examine how PEG terminal chemistry and antibody maturation modulate these interactions. Methoxy- (m-PEG) and hydroxy-terminated PEG (HO-PEG) were tested against Fv-clasps from two anti-PEG IgMs: the naïve IgM M9 and the affinity-matured IgM M11. M11 bound PEG more strongly and at shorter rupture distances than M9, with 2D force–distance maps revealing the most intense signatures for M11 and m-PEG pair. Complementary quartz crystal microbalance with dissipation (QCM-D) and Fourier-transform infrared (FTIR) spectroscopy confirmed higher binding by M11 and a terminal preference of M9 for m-PEG. In addition to antibody maturation, we report that the hydrated structure of PEG plays a significant role in PEG–antibody binding. HO-PEG forms extended, hydrated layers, whereas m-PEG adopts compact, collapsed conformations, shaping antibody accessibility and binding mechanics. These results provide molecular-level insight into how antibody structure and PEG hydration state dictate binding, offering design principles for PEGylated therapeutics with reduced immunogenicity and improved performance.

Ulvan, a sulfated marine polysaccharide, holds promise for antiadhesive and antimicrobial surface coatings. We engineered two ulvan-based coating series by covalently grafting ulvan onto poly(allylamine)-modified substrates using EDC/s-NHS or BDDE cross-linking chemistries. Surface analyses confirmed tunable morphology and composition with coating thickness and ulvan density saturated at defined cross-linker thresholds. Adhesion assays with Escherichia coli and Staphylococcus aureus revealed significantly reduced colonization on all ulvan coatings versus uncoated controls. E. coli adhesion decreased exponentially with ulvan density with nanogel-like coatings also inducing membrane damage. S. aureus exhibited weaker transient responses, possibly due to structural resistance. Correlating biological activity with surface chemistry established ulvan content as a key predictor of performance. These coatings offer short-term protection against microbial colonization, particularly effective during the critical early adhesion phase, and provide a chemically tunable platform for anti-infective surfaces in applications such as catheters, wound dressings, and food-contact materials. This work lays the groundwork for designing glycosylated interfaces in biomedical and environmental applications where early stage biofilm prevention is critical.

Biomembranes evolved to protect cells and regulate exchange, forming a powerful barrier to large, charged macromolecules such as nucleic acids. In recent years, this paradigm has been competently overturned by soft biomaterials based on cell-penetrating peptides (CPPs). Herein, we investigate and compare the structural dynamics of peptiplexes formed between DNA and two cationic CPPs, TAT-HIV and NLS-SV40T. Combining experimental approaches and molecular dynamics (MD) simulations, we examined peptiplexes across mesoscopic scales to elucidate their supramolecular assembly and correlate these features with cellular uptake. We found that peptiplexes based on TAT-HIV exhibit greater structural flexibility, adopting ordered secondary structures and self-assembling into clusters and nanofibrils. In contrast, NLS-SV40T/DNA complexes retain random coil configurations, forming globule-studded coiled nanoassemblies with internal 2D hexagonal columnar phases. Calorimetry data indicated that TAT-HIV/DNA complexation is more favorable and exothermic, whereas NLS-SV40T binding to DNA is weaker and endothermic. MD simulations supported the experiments by showing that NLS-SV40T moves across DNA strands, settling into major grooves, whereas TAT-HIV bridges major and minor grooves via persistent arginine-mediated H-bonds and stronger energetics. Cell uptake assays showed that NLS-SV40T/DNA peptiplexes are internalized comparatively more efficiently, likely due to their more compact organization and lower lytic potential. Conversely, TAT-HIV induces membrane damage, as observed by atomic force microscopy, suggesting that its stronger electrostatics and enhanced H-bonding capacity may contribute to lytic activity. The findings presented here bring mechanistic insights into the structural landscape of peptiplexes, improving the rationale that supports the design of peptide-mediated gene delivery materials.

This study investigates a rapid, cost-effective method for brain stroke detection using a Recessed Drain (RD) Heterojunction (HJ) Vertically Stacked (VS), Gate-All-Around (GAA), and Nanosheet (NS) Tunneling Field-Effect Transistor (TFET) biosensor. The core innovation lies in the three vertically stacked Silicon nanosheet channels, which provide an expanded sensing surface, enhanced electrostatic control, and improved biomolecule interaction compared to single-channel devices. The proposed RD-HJ-VS-GAA-NS-TFET outperforms conventional biosensor architectures such as planar MOSFETs, multigate FETs, and nanowire FETs, due to its wider channel and multilayered design. To address strain effects arising from silicon growth on SiGe, a comparative analysis between conventional silicon and strained silicon nanosheet channels is explicitly performed. The sensitivity analysis is carried out by examining key parameters, including the Drain Current (I_D) response, Subthreshold Swing behavior (SS), and the switching ratio (I_ON/I_OFF). The dielectric constant exhibits significant variation between healthy and stroke-affected brain tissues due to the distinct electromagnetic properties of brain tissues, particularly when they interact with nanocavities at high frequencies. Device performance is analyzed with respect to cavity length, cavity thickness, gate work function configurations, cavity orientation, filling factor, and nonuniform step profiles. The I_ON/I_OFF ratio increases from 3.58 × 10¹¹ under hemorrhagic state (k = 30) to 5.40 × 10¹¹ under healthy state (k = 42) and further to 1.05 × 10¹² under ischemic state (k = 61), highlighting the improved switching characteristics of the proposed biosensor, which is crucial for effectively distinguishing between stroke-affected and healthy brain tissues. The proposed RD-HJ-VS-GAA-NS-TFET biosensor shows strong potential as a label-free, Point-Of-Care (POC) diagnostic platform for rapid and accurate stroke detection.

Although complexes with polycationic carriers have been proposed for the skeletal muscle delivery of plasmid DNA (pDNA), there is a problem in reducing the effect due to nonspecific aggregation in vivo caused by multiple cationic charges. Therefore, we have synthesized a thymine end-modified poly(ethylene glycol) (Thy-PEG) as a potentially nonionic single-nucleobase end-modified PEG and designed to form a complex by hydrogen bonding with pDNA whose duplex was partially dissociated by annealing. Then, the local administration of the resulting Thy-PEG/pDNA complex with a PEG chain length of 5k and a [Thy]_Thy-PEG/[Base]_pDNA ratio of 0.5 to the tibialis muscle of mice resulted in a tendency for a 14-fold increase in expression, as compared to that of annealed naked pDNA. In this study, the created Thy-PEG/pDNA complexes, that is, single-nucleobase-terminal complexes (SNTCs), can offer a unique cation-free pDNA delivery platform in vivo.

Wound healing remains a major clinical challenge, especially in the management of chronic and infected wounds, where conventional dressings often fall short in providing antimicrobial protection, moisture regulation, and support for tissue regeneration. To overcome these limitations, this study presents the development of a hydrogel-based wound dressing composed of minocycline hydrochloride and AgO-ZnO nanostructures in a Poly(vinyl alcohol) (PVA)/Pectin matrix reinforced with bacterial nanocellulose (BNC) and tempo-oxidized bacterial nanocellulose (TOBNC) derived from kombucha biomass. AgO-ZnO nanoparticles were synthesized via chemical precipitation, while BNC was isolated using kombucha fermentation. The resulting hydrogel patches were fabricated and characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), UV–visible (UV–vis), Fourier transform infrared spectroscopy, and FESEM to confirm structural, morphological, and functional integration. Thorough investigations included antibacterial efficacy (<15% Viability), water vapor transmission (WVTR) (∼2250 g/m²·day), swelling behavior, cell migration (85 ± 0.16%), enzymatic degradation (∼22 ± 0.27%), and drug release profiling. The hydrogel patches exhibited high water uptake, controlled degradation, and strong antibacterial activity against common wound pathogens. This study underscores the potential of integrating organic and inorganic fillers along with minocycline to create advanced wound dressings. This work not only meets the structural and functional requirements of modern wound care but also advances the development of sustainable biomedical materials.

Despite extensive efforts to develop nanoparticle-based radioenhancers, clinical translation remains limited, partly due to the lack of physiologically relevant preclinical models. To address this gap, we developed a 3D spheroid model of head and neck cancer using FaDu cells and compared it directly to a corresponding in vivo model in a radiotherapy setting. The spheroids exhibited key tumor-like features, including the formation of a hypoxic core and growth kinetics similar to those of in vivo tumors. Importantly, the model allowed for long-term monitoring of tumor growth and radiation response. Upon X-ray irradiation, the dose–response behavior in spheroids mirrored that observed in vivo. Furthermore, TiO₂, HfO₂, and Au nanoparticles demonstrated consistent radiosensitization effects in both systems when matched for the uptake mass. In contrast, conventional 2D clonogenic assays failed to align with in vivo performance, likely due to their lower radioresistance and unrealistic nanoparticle exposure conditions. This study introduces a robust, scalable, and clinically compatible 3D in vitro platform for the preclinical screening of nanoparticle radioenhancers. The system may offer streamlining of development pipelines and support the 3R principles of reduction, replacement, and refinement in radiation oncology research.