ACS Applied Bio Materials最新文献

Supraparticles (SPs) are secondary particles formed through nanoparticle self-assembly with porous architectures and bioinspired structural features suitable for drug delivery applications. Although binder-mediated structural control influences SP assembly, how different loaded drugs systematically alter amyloid nanofibril (ANF) and SP structures remains unclear. In this study, neutral, basic, and acidic model drugs—acetaminophen (ACP), fluconazole (FCZ), and proglumide (PGM), respectively—were incorporated into spray-dried SPs composed of silica nanoparticles (SiNPs) and ANFs to investigate the effects of drug properties on SP structure and release behavior. All drugs exhibited nearly 100% loading efficiency, and powder X-ray diffraction analysis revealed that they were in an amorphous state within the SPs. ACP- and FCZ-loaded SPs maintained their characteristic ANF-induced wrinkled morphology, whereas PGM-loaded SPs exhibited a pronounced loss of wrinkling at pH 2, indicating that acidic drugs can disrupt ANF-mediated assembly during SP formulation. Drug release studies further showed that ANFs suppressed the initial burst release and slowed the overall release by restricting diffusion pathways within the SP structures. This suppression was the most pronounced in PGM-loaded SPs, likely owing to drug retention within the assembled ANF domains. These findings demonstrate that drug acid–base properties critically modulate SP morphology and release behavior, highlighting the importance of drug–biomaterial interactions in designing SP-based delivery platforms.

Gas therapy offers powerful clinical potential but remains limited by poor control of gas concentration, localization, and stability. Microporous materials, particularly metal–organic frameworks and zeolites, present a path toward precision gas therapy by allowing selective adsorption, protection, and controlled release of therapeutic gases such as oxygen, nitric oxide, carbon monoxide, and hydrogen sulfide. Their permanent porosity, tunable pore size, and active metal centers enable the design of materials that respond to biological or external stimuli with high selectivity. This review highlights how structural and chemical control within microporous materials determines gas-storage and -delivery performance, with emphasis on emerging biomedical applications. The discussion includes recent advances in material synthesis, gas loading mechanisms, and biological evaluation, outlining how microporous materials can overcome current barriers in therapeutic gas administration. Future opportunities are presented for translating these frameworks into safe, efficient, and clinically adaptable systems for precision medical treatment.

In this work we explore a plasma-assisted, solvent-free synthesis of hydroxyapatite nanoparticles (HAp NPs) by exposing the precursors (i.e. CaCl₂ and (NH₄)₂HPO₄) solely to N₂ and O₂ plasma gases at different powers and treatment times. Depending on the plasma generation conditions, different calcium phosphate (CaP) phases are formed in addition to HAp, including octacalcium phosphate (OCP) and dicalcium phosphate dihydrate (DCPD). The conditions identified as the most favorable for the plasma-assisted synthesis of HAp, in terms of preferential formation of HAp over OCP and DCPD, reaction completion, and conversion efficiency of the reagents into HAp, consist of using O₂ at 0.8 mbar as the working gas, with a plasma power of 50% and a treatment time of 300 s. HRTEM studies demonstrate that, under these operating conditions, plasma-assisted synthesis predominantly yields crystalline HAp nanoparticles (NPs) with average size of 5.5 ± 2.5 nm. The synthesized ultra-small HAp NPs are incorporated into Ca²⁺-mediated alginate (Alg) hydrogels to assess their potential as both nanofillers and crosslinking agents for improving hydrogel stability under Ca²⁺-free conditions. While the incorporation of HAp NPs does not significantly affect the hydrophilicity or overall structure of the Alg network, it markedly influences the stiffness and gelation process through the interactions between Alg carboxylate groups and the Ca²⁺ ions located in the HAp crystal lattice. The results demonstrate that ultra-small HAp NPs can function as secondary crosslinking agents, increasing the crosslinking density and strengthening the hydrogel network, when the Alg binding sites are not already saturated by Ca²⁺ ions supplied by CaCl₂.

The integration of microneedles (MNs) with electrochemical biosensors is a promising strategy for minimally invasive detection of metabolites from interstitial fluid (ISF). Conventional MN-based sensing platforms typically rely on conductive coatings or surface functionalization of MNs to obtain an electrochemical signal. However, such modifications increase fabrication steps, reduce dermal biocompatibility, and compromise their structural integrity during skin insertion. Here, we have integrated chitosan MNs with a printed electrochemical sensor (i.e., laser-scribed graphene; LSG) without modifying the needle surface for the non-enzymatic detection of uric acid (UA). For this, a filter paper disc was sandwiched between the MN array and the printed LSG sensor for efficient absorption and uniform distribution of a small volume of ISF collected from the artificial skin via MNs to form a complete electrochemical circuit. The developed MNs-integrated paper-interfaced LSG (MNs-P-LSG) sensor exhibited diffusion-controlled charge transfer behavior, with an apparent diffusion coefficient of 2.97 × 10^–5 cm²s^–1. The sensor exhibits a linear detection range from 100 to 1000 μM with a sensitivity of 0.006 μAμM^–1 i.e. 0.053 μAμM^–1cm^–2 and a limit of detection of 91 μM, covering the clinically relevant range. Validation studies performed using artificial ISF incorporated into phantom gel (artificial skin) showed recovery deviations of up to 15%, indicating acceptable analytical accuracy. Thus, the developed MNs-P-LSG sensor enables enzyme-free, minimally invasive detection of UA without surface modification of MNs.

The development of advanced three-dimensional (3D) scaffolds for cancer modeling and drug screening remains a critical need in biomedical engineering. Most 3D printed scaffolds for cell growth focus on a tessellated design involving sequentially deposited printed fibers. Although this design offers a high degree of flexibility in scaffold dimensions, including fiber width and inter-fiber spacing, continuous voids in the Z-axis require additional methods to avoid cell sedimentation to the underlying substrate such as the incorporation of support materials. In this work, we present a modified design strategy based on the rotation of the internal infill pattern between successive layers. This strategy yields tessellated scaffolds that significantly improve cell retention and spatial cell distribution with no need for additional support matrices. Using this optimized design, we developed a 3D breast cancer model to investigate chemotherapeutic resistance by comparing MDA-MB-231 cells and their corresponding cancer stem cells, under paclitaxel treatment. The incorporation of gold nanorods in the scaffold matrix allowed us to perform real-time, in situ drug monitoring via surface-enhanced Raman scattering (SERS) sensing. These tessellated plasmonic scaffolds enable the evaluation of chemoresistance by tracking differential drug accumulation in 3D.

We report a one-step biosynthesis of silver nanoparticles (Fa-AgNPs) using an aqueous Fagonia indica extract and benchmark their activity at the nano-fungal biointerface against Candida albicans and the emerging, multidrug-resistant pathogen Candida auris. Fa-AgNPs were polydisperse and quasi-spherical, with a smaller mean diameter than citrate-capped chemically synthesized AgNPs (Cs-AgNPs) (19.41 ± 7.32 nm vs. 29.01 ± 2.63 nm). Fa-AgNPs outperformed Cs-AgNPs on both species, with MICs of 31.25 vs 125 µg/mL against C. albicans and 3.91 vs 7.81 µg/mL against azole-resistant C. auris. Against C. auris, Fa-AgNPs were at least 64-fold more potent than fluconazole (3.91 vs >250 µg/mL). To our knowledge, this is the first report of F. indica-mediated AgNPs achieving an MIC below 4 µg/mL against this pathogen. Mechanistically, Fa-AgNPs delayed the onset of growth, elevated intracellular ROS in C. albicans, and induced catalase-based antioxidant defense in both species; SEM showed loss of budding cells and extracellular polymeric substances, together with a transition from smooth to rough surfaces and cell-wall damage, in both species, consistent with a primarily oxidative interfacial mechanism. Hemolysis assays indicated acceptable blood compatibility at the lowest concentration tested (2.5 µg/mL), with hemolysis increasing at higher concentrations.

A major limitation across nanoparticle delivery platforms is inefficient intracellular delivery following cellular uptake, often resulting from sequestration within endosomal compartments. Here, we show that peptide architecture can influence intracellular trafficking and reduce accumulation within early endosomal compartments in lipid–protein nanocarriers. Specifically, we fuse R6W3 (RRWWRRWRR), an amphipathic cell penetrating peptide, to the N- or C-terminus of the nanodisc scaffold proteins and systematically evaluate its impact on membrane interactions and cellular behavior. Structural and biophysical characterization confirms that R6W3 incorporation preserves nanodisc assembly and protein–lipid interactions, enabling direct attribution of functional differences to peptide-driven interfacial effects. R6W3-functionalized nanodiscs exhibit enhanced membrane binding and cellular uptake, with N-terminal fusion producing the strongest interfacial interactions. In live cells, R6W3 functionalization increases endocytic activity, evidenced by increased formation of clathrin-coated pits and intracellular colocalization with clathrin-coated vesicles. Notably, R6W3-functionalized nanodiscs display reduced accumulation in early endosomes relative to unmodified nanodiscs, consistent with altered intracellular trafficking following endocytic uptake. Functionally, doxorubicin-loaded, R6W3-functionalized nanodiscs produced a greater reduction in cell viability than unmodified controls at equivalent concentrations. Together, these results demonstrate that R6W3 functionalization is an important design consideration for modulating nanodisc-cell interactions, from membrane association and cellular uptake to intracellular trafficking. These findings provide a framework for engineering nanodisc-based delivery systems with improved intracellular access.

Bacterial-infected wounds remain an intractable global health issue due to the escalation of antibiotic resistance and the dysregulated inflammatory microenvironment, while conventional therapies fail to achieve antibacterial and anti-inflammatory effects simultaneously. Herein, a multifunctional cobalt single-atom nanozyme-berberine (Co SA/B) nanoplatform is fabricated for bacterial-infected wound repair, integrating the multi-enzyme catalytic and photothermal properties of single-atom nanozymes with the natural bioactivities of berberine (BBR). The atomically dispersed Co sites endow the platform with multiple enzyme-like activities to trigger reactive oxygen species generation, bacterial glutathione depletion, and wound hypoxia relief, thereby eliminating pathogens via oxidative stress. Under 808 nm laser irradiation, the Co SA carbon matrix exhibits prominent photothermal performance, realizing photothermal therapy and further boosting catalytic activity. Loaded BBR synergistically reinforces antibacterial efficacy and modulates the inflammatory microenvironment by inducing M1-to-M2 macrophage repolarization, relieving local inflammation, and promoting tissue regeneration. In vitro experiments verify that Co SA/B combined with a near-infrared (NIR) laser efficiently eradicates Staphylococcus aureus (S. aureus) and Escherichia coli, disrupts bacterial biofilms/membranes with negligible cytotoxicity to normal cells. In vivo evaluations of a S. aureus-infected mouse abscess model confirm that Co SA/B achieves photothermal–catalytic synergistic therapy, significantly inhibiting bacterial colonization, alleviating inflammatory infiltration, and promoting epidermal regeneration and collagen deposition, with excellent in vivo biosafety. This work initiates the combination of single-atom nanozymes and natural herbal bioactive ingredients to synergistically tune oxidative stress levels and the inflammatory microenvironment, presenting an antibiotic-free intervention for bacterial-infected wound repair.

This study examines bench-scale synthesis and the physicochemical and functional properties of hemoglobin (Hb) formulations, including bovine (bHb), human (hHb), and pyridoxylated (PLP, pyridoxal-5′-phosphate) human Hb (PLP-hHb), along with their poly(ethylene glycol) (PEG)-conjugated counterparts. These PEGylated Hb constructs were synthesized via an inside-out strategy targeting the β-Cys93 residue of Hb using a four-arm PEG-maleimide molecule (MW = 20 kDa per arm; 80 kDa total), producing multi-arm PEG conjugated Hbs (MA-PEG-Hbs). The precursor Hbs exist as α₂β₂ tetramers (MW ∼64–65 kDa; diameter ∼5 nm), whereas MA-PEG-Hbs showed increased size (320–345 kDa; ∼14 nm), consistent with 3–4 Hb tetramers per PEG scaffold. This expansion reduced haptoglobin binding kinetics by ∼6–9-fold, potentially prolonging circulation and reducing renal clearance. Circular dichroism confirmed preservation of α-helical structure and heme integrity, while thermal stability decreased but remained within 63–66 °C. Bench-scale synthesis demonstrated scalability, with MA-PEG-hHb achieving the highest yield (∼84 ± 8%). Oxygen-binding studies showed preserved cooperativity and increased affinity (lower P₅₀): MA-PEG-bHb (16.2 ± 0.6 mm Hg), MA-PEG-hHb (6.88 ± 0.10 mm Hg), and MA-PEG-PLP-hHb (8.87 ± 0.27 mm Hg), with cooperativity coefficients of 2.1 ± 0.1, 2.2 ± 0.01, and 1.7 ± 0.03. These contrast with Hemospan (P₅₀ = 6 ± 2 mm Hg; cooperativity 1.2 ± 0.5). Hemospan was synthesized by surface PEGylation of thiolated hHb with 5 kDa maleimide-PEG, suggesting that high oxygen affinity HBOCs such as the MA-PEG-Hbs variants may benefit in targeting ischemic tissues with extremely low oxygen tension. Oxidative analysis showed increased auto-oxidation after PEGylation (bHb: 0.010 → 0.026 h⁻¹; hHb: 0.007 → 0.013 h⁻¹; PLP-hHb: 0.011 → 0.015 h⁻¹), comparable to Hemospan (0.007 → 0.021 h⁻¹). Overall, multi-arm PEGylation enhances the molecular size, increases oxygen affinity, and circulation potential while maintaining oxidative behavior within ranges observed for commercial HBOCs, highlighting a balance between functional performance and biochemical stability.

Light-responsive photocages are attractive tools for controlled drug delivery, yet achieving efficient photo-release in aqueous media remains challenging. Herein, a symmetrical BODIPY bis(oxime ester) derivative (BD-diOE) was developed for visible-light-triggered release of valproic acid (VPA). The study confirmed a sequential photo-uncaging process resulting in the release of two equivalents of VPA. To improve aqueous performance, BD-diOE was encapsulated into Pluronic F127 micelles (BD-diOE@F127). Quantitative analysis revealed that BD-diOE@F127 in water releases approximately 30% more VPA than BD-diOE in a methanol–mixed water solvent under identical irradiation conditions. Moreover, BD-diOE@F127 exhibited pronounced light-dependent in vitro cytotoxicity. These results demonstrate that the combination of symmetric molecular design and micelle formulation provides a promising platform for photo-responsive biomaterials and controlled drug delivery applications.