ACS Applied Bio Materials最新文献

Coordination compounds were synthesized and structurally characterized containing biocompatible alkaline earth metal ions and the bone-seeking agents clodronate (CLOD, (dichloromethanediyl)bis(phosphonate)) and medronate (MED, methylenediphosphonate). Dimensionality in these structures ranges from 0D (Mg-CLOD, Ca-CLOD) to 1D (Ca-CLOD-CP) to 2D (Ca-MED, Sr-CLOD). The salt Na₂–CLOD (used as a reference) and the CLOD coordination compounds with Mg²⁺, Ca²⁺, and Sr²⁺ were utilized as controlled release systems (excipient-containing tablets) of the active drug CLOD in acidic conditions that mimic the human stomach (pH = 1.3). Release of Ca²⁺ ions from the Ca-CLOD system was also monitored. The same experiments were carried out for the MED and Ca-MED systems. The drug release profiles were compared, and it was found that all Mg/Ca/Sr-containing compounds exhibit variable deceleration of the “active” CLOD release compared to the Na-containing reference. The calculated initial rates (μmol CLOD/min) followed the order Na (1.67) > Mg (1.32) > Sr (0.97) > Ca (0.81/0.70). The values were 1.44 and 0.57 for the MED and Ca-MED systems. This behavior was rationalized based on the structural idiosyncrasies of each system. The overall drug release profile for each system was the result of several structural factors, such as H-bonding interactions, strength of the metal–O(phosphonate) bonds, and packing density, but also crystal morphological/textural factors. These compounds were also tested for their toxicity at the concentration of 100 μM in vitro (micronucleus assay) and in vivo (brine shrimp Artemia salina) and were found to be of low toxicity.

Morphine-induced analgesic tolerance limits its clinical use. This study shows that metformin alleviates such tolerance by inhibiting the TXNIP/NLRP3/GSDMD axis, reducing microglial activation and proinflammatory cytokines in CD-1 mice (metformin 200 mg/kg i.p.; morphine 10 mg/kg s.c.) and BV-2 cells (metformin 100 μM; morphine 200 μM). TXNIP is critical, as its overexpression weakens metformin’s effect. The TXNIP siRNA/metformin coloaded TM@ZIF-8/HA nanosystem enhances efficacy via pH-responsive, CD44-targeted delivery with good biocompatibility, providing a perioperative pain management strategy.

Nature serves as an inexhaustible source of inspiration for advanced material design. While nature-inspired nonliving materials exhibit exceptional properties, they typically lack the dynamic functionalities of living systems, such as self-healing and environmental responsiveness. To bridge this gap, living materials, which integrate living cells (e.g., bacteria, fungi, algae) within abiotic matrices, have emerged as transformative platforms. These materials harness cellular functions (e.g., biomineralization, programmable metabolism) to achieve unprecedented adaptability and sustainability. In this review, we categorized living materials into two distinct types based on the role of the cells: (1) cells acting as platforms for material synthesis and (2) cells integrated as components of materials for functionalization. We summarized the characteristics of living and nonliving materials inspired by nature, with applications of living materials in energy, medicine, catalysis, concrete, and soft robotics. We further discussed advanced manufacturing techniques for living materials. We envision that the design principles of living materials will advance health, energy, and sustainability.

Cardiovascular disease (CVD) remains the leading cause of death worldwide, with small-diameter vascular grafts (SDVGs, less than 6 mm) presenting significant clinical challenges due to high failure rates from thrombosis, intimal hyperplasia, and compliance mismatch. Vascular tissue engineering (VTE) seeks to address these limitations by developing biocompatible, mechanically robust scaffolds that closely mimic native blood vessels. In this study, we focused on the fabrication and characterization of co-electrospun nanofibers composed of varying weight ratios of polyethylene terephthalate (PET) and polyurethane (PU). The structural analysis using field emission scanning electron microscopy (FE-SEM) revealed that all scaffolds exhibited uniformly distributed, bead-free, and randomly oriented fibers, except for the PET/PU (50:50) and (75:25) scaffolds, which presented a few beads. PET/PU nanofibrous scaffolds exhibited significantly smaller fiber diameters compared to pure scaffolds. Porosity percentage varied from 63.00 ± 0.46% for pure PU to 82.00 ± 2.1% for PET/PU (90:10), aligning well with the optimal range for cell proliferation. Fourier transform infrared spectroscopy (FTIR) confirmed the successful co-electrospinning of PET and PU, as evidenced by characteristic peaks consistently present across all composite scaffolds. Mechanical properties of PET/PU (75:25) and (25:75) as optimal composites achieve tensile strengths of 5.4 ± 0.69 and 4.73 ± 0.31 MPa and Young’s moduli of 44.4 ± 1.08 and 49.07 ± 1.59 MPa, closely approximating native vascular tissue properties. Burst pressure demonstrated that composite scaffolds containing more than 50% PET exceeded the clinically relevant threshold of 2000 mmHg. Compliance values were modulated by the PU content, with increasing PU proportions enhancing compliance, ranging from 5.04 ± 0.78% in PET/PU (90:10) to 8.84 ± 0.1% in PET/PU (10:90), thereby illustrating the tunable mechanical response attainable through polymer composite engineering. Biocompatibility assays confirmed significant NIH/3T3 cell viability increases on all scaffolds, notably a 3.8 time rise on PET/PU (25:75) nanofibrous composites by day 7, with preserved healthy cell morphology. In vivo assessments via rat and sheep carotid artery implantation demonstrated moderate, controlled inflammatory responses, effective tissue integration, and high long-term patency without thrombosis or hyperplasia up to 8 months, verified by histopathology and Doppler ultrasound. These results validate that co-electrospun PET/PU scaffolds, particularly at (75:25) and (25:75) ratios, exhibit a favorable combination of structural, mechanical, and biological properties suitable for SDVG applications.

Conventional dexamethasone eye drops suffer from poor ocular bioavailability due to rapid tear turnover and limited corneal residence, necessitating frequent dosing and posing challenges in chronic ocular therapies. This study addresses the need for a sustained and biocompatible ocular delivery platform by engineering hydrogel contact lenses incorporating dual-surfactant micelles for prolonged dexamethasone release. Micelles were prepared using Pluronic P123 and TPGS at different weight ratios, with a total surfactant concentration of 0.1% w/v─ten times above their critical micelle concentration─to optimize drug solubilization and encapsulation. DLS confirmed nanoscale micelles (∼11–14 nm) with a narrow size distribution. Compared to conventional soaking and single-surfactant systems, mixed micelle-laden lenses achieved significantly higher drug loading (59.1  ±  11.5 μg), minimized leaching during sterilization, and reduced burst release. In vitro release extended over 96 h with sustained flux. In vivo studies in rabbits demonstrated a >20-fold improvement in bioavailability (AUC_0–24 = 579 μg·h/mL) and extended mean residence time (8.8 h) compared to eye drops, maintaining therapeutic tear concentrations for 24 h postapplication. The formulation also suppressed inflammatory IL-6 levels to near baseline, outperforming eye drops and soaked lenses. Cytotoxicity (96.3% viability) and ocular irritation tests confirmed excellent biocompatibility. In conclusion, this dual-surfactant micelle platform markedly enhances the therapeutic potential of drug-eluting contact lenses, offering a safe, sustained, and patient-compliant alternative for managing ocular inflammation. These findings support further clinical translation of micelle-integrated lenses as next-generation ocular drug delivery systems.

Although natural killer (NK) cells are key players in the immune response against tumors, their performance is restricted when it comes to solid cancers like triple-negative breast cancer (TNBC). This study proposes an NK cell-mediated immunotherapy strategy that enhances NK cytotoxicity by modulating the stiffness of TNBC cells through mechanical vibration. Using an in vitro model with MDA-MB-231 cells, a vibration culture system (1.0 g at 50 Hz, 1 min stimulus/1 min rest for 1 h) was applied to increase cell stiffness. Cytotoxicity assays revealed a 2.45-fold increase in NK cell-mediated killing of stiffened MDA-MB-231 cells compared to controls. Immunofluorescence, RT-qPCR, and calcium flux assays demonstrated enhanced NK cell activation, including improved target recognition, mechanosensitive ion channel activation, calcium influx, lytic granule release, and cytokine responses. These findings suggest that mechanical vibration-induced tumor cell stiffening is a promising, noninvasive strategy to improve NK cell function and enhance tumor immunotherapy.

This study proposes quaternized lignin (QL) as a sustainable and multifunctional additive for active food packaging applications and presents the development of fish gelatin (FG)-based nanofiber packaging materials. Cationic QL was synthesized via glycidyltrimethylammonium chloride (GTMAC) modification of kraft lignin to enhance its water dispersibility and antimicrobial properties. The resulting QL derivatives were incorporated into FG-based nanofibers via electrospinning, which were stabilized through Maillard reaction-induced cross-linking. The quaternization degree and incorporation of QL into FG nanofibers considerably affected the nanofiber morphology, mechanical properties, hydrophilicity, and structural stability. Antioxidant and antibacterial assays revealed that FG-based QL (FG/QL) nanofibers, especially those containing highly quaternized lignin (QL3), exhibited enhanced radical scavenging and bactericidal activities againstStaphylococcus aureus and Escherichia coli, which were attributed to the synergistic effect of QL and Maillard reaction products. The blueberry preservation test confirmed the practical efficacy of Maillard reaction-cross-linked FG/QL3 nanofibers in extending shelf life by inhibiting microbial spoilage. These results indicated that QL-functionalized FG nanofibers have potential applicability as biodegradable natural materials for active food packaging systems.

With coronary artery disease remaining the leading cause of mortality worldwide, the design and manufacture of clinically viable synthetic coronary artery grafts remains a fundamental healthcare challenge. It is widely accepted that vascular mimicking materials (VMMs) should emulate the heterogeneous biomechanical and biological functions of the multilayered artery wall to ensure long-term patency postimplantation. However, few VMMs can adequately meet these complex design requirements. Poly(vinyl alcohol) (PVA)/gelatin cryogels are prospective VMMs due to their combined mechanical (PVA) and biointegrative (gelatin) features, but their development thus far has been limited to homogeneous constructs. The aim of this research is to assess the mechanical response of biomimetically designed multilayered grafts, simulated using Finite Element Analysis. The impact of a sinusoidal interface on circumferential stress distribution and graft compliance, was explored. Using qualitative insight from research on hydrogel based functionally graded biomaterials, and in the context of subzero extrusion additive manufacturing, rough (infinite) friction was used to model the contact between the layer. It was found that transmural stress patterns were continuously graded (phased) as a function of interface amplitude and frequency. In contrast to laminated models, which displayed a discontinuity in transmural stress between layers. This design methodology illustrates a novel approach to achieving functionally graded synthetic grafts through interface design.

Mitochondria have emerged as critical therapeutic targets in anticancer strategies, particularly for overcoming the inherent resistance challenges during tumor treatment. Herein, we present a metallodrug delivery system (FT-lipoAu/PTX) with multistage targeting capability, designed to achieve mitochondria-specific photothermal apoptosis and reverse tumor chemoresistance. FT-lipoAu/PTX was composed of folic acid (FA) and triphenylphosphonium (TPP)-modified paclitaxel (PTX) liposomes encapsulating gold nanorods (AuNRs). FA and TPP dual modification enable multistage targeting of folate receptor-overexpressing breast tumor cells, facilitating FT-lipoAu/PTX accumulation in mitochondria. Under near-infrared (NIR) laser irradiation, FT-lipoAu/PTX generated localized hyperthermia, triggering mitochondrial membrane potential depolarization, cytochrome c release, reduced cellular metabolic efficiency, and suppressed ATP synthesis. Importantly, this tumor metabolic reprogramming process significantly downregulated drug-resistance protein expression [e.g., efflux pump P-glycoprotein (P-gp)], thereby increasing intracellular PTX retention and enhancing chemotherapeutic efficacy. In a chemoresistant breast tumor murine model, FT-lipoAu/PTX demonstrated prolonged circulation, high tumor specificity, potent tumor growth suppression, and minimal systemic toxicity. Collectively, FT-lipoAu/PTX leveraged mitochondria-targeted phototherapy to overcome chemoresistance barriers, providing a robust strategy for effective chemotherapy.

RNA interference (RNAi)-based biopesticides offer precise pest control with minimal environmental impact, yet their field efficacy is limited by rapid degradation of double-stranded RNA (dsRNA) due to UV exposure, nucleases, and poor foliar adhesion. To address these challenges, we developed a mineral oil-based water-in-oil (W/O) emulsion to encapsulate dsRNA targeting the Amphitetranychus viennensis V-ATPase A gene. The formulation was optimized through hydrophilic–lipophilic balance (HLB) screening (optimal HLB = 10), ternary phase ratio adjustment (oil:water:surfactant = 64:20:16), and dsRNA loading concentration tests (optimal: 5000 mg/L). Bioassays assessed toxicity against eggs, nymphs, and adults of Amphitetranychus viennensis, alongside field trials comparing dsRNA@W/O (750× dilution) with naked dsRNA, double-applied naked dsRNA, and the chemical control etoxazole. Key findings demonstrated that dsRNA@W/O significantly enhanced stability: after 72 h of UV/air exposure, 93.67% of activity was retained, compared to complete degradation of naked dsRNA. The formulation accelerated lethality, reducing median lethal time (LT₅₀) from 4.84 to 1.95 days for nymphs and from 4.82 to 2.65 days for adults. Field efficacy at 20 days post-treatment reached 85.75% at 1.33 mg/L dsRNA, outperforming naked dsRNA (62.79%) and approaching etoxazole (95.69%), while using one-third the active ingredient of conventional dsRNA treatments. This work demonstrates a cost-effective, scalable mineral oil encapsulation strategy that synergizes RNAi-mediated pest control with mineral oil’s physical effects, offering a sustainable, environmentally safe, and economically feasible pest management approach.