ACS Applied Materials & Interfaces

Fetuin-A is a plasma protein of interest for bone-interfacing applications due to its role in mineralization processes through calcium/phosphate ion-binding capabilities. However, the role of fetuin-A in the initial stages of cellular interaction with biomaterials and the mechanisms involved are not fully clear. This work investigated the response of osteoblast-like Saos-2 cells to model gold substrates presenting pre-adsorbed fetuin-A as a surface modification, to determine the role of the protein in cell attachment and proliferation. Correlative quartz crystal microbalance with dissipation (QCM-D), surface plasmon resonance, and radiolabeling confirmed fetuin-A adsorbed on model surfaces in similar quantities compared to serum albumin but formed a less packed layer with increased water entrapment. Surfaces presenting pre-adsorbed fetuin-A enhanced cellular adhesion, similar to fibronectin, but attached cells displayed morphological characteristics more similar to those with pre-adsorbed albumin, with lower average surface area and maximum axis. Over 3 days, fetuin-A exhibited lower cellular proliferation compared to the fibronectin control, likely correlated to the decrease in cellular metabolism observed at the same time-point, and persisted over 7 days. These results provide insight into the role of adsorbed fetuin-A for bone-interfacing implant applications, suggesting the pre-adsorption of the protein alone aids cellular attachment, but is not sufficient to promote early stages of osseointegration.

Indwelling medical devices such as catheters and endotracheal tubes are major drivers of hospital-acquired morbidity and mortality due to bacterial colonization. The resulting healthcare-associated infections (HAIs) are further exacerbated by rising antimicrobial resistance, underscoring the urgent need for strategies that both prevent biofilm formation and reduce reliance on antibiotics. Polyvinyl chloride (PVC), a widely used material in medical tubing, is highly prone to bacterial attachment, making it a critical target for intervention. Here, we show that complete eradication of Staphylococcus aureus--both sessile on PVC and planktonic--can be achieved using a bovine serum albumin (BSA) amyloid-like coating in combination with vancomycin at a dose eight times lower than the MIC. While the amyloid film alone markedly reduces bacterial adhesion, the residual bacterial load still reaches infection-risk thresholds. This dual approach therefore not only prevents biofilm development but also significantly lowers antibiotic requirements, reducing the risk of resistance emergence and improving therapeutic safety. The coatings, deposited on PVC and on glass (as a model surface), were synthesized using dithiothreitol (DTT) as a reducing agent, as alternative to tris(2-carboxyethyl)phosphine (TCEP). Through optimization of the synthesis, the resulting films preserved their physicochemical and anti-biofouling properties while offering a simple, low-cost, and scalable approach. The coatings strongly adhere to both substrates, remain stable under aqueous and mechanical stress, and effectively suppress bacterial and mammalian cell adhesion without cytotoxicity. These properties are clinically relevant, reducing infection risk and mitigating tubing failure due to fibrous capsule formation, encasement, or crystallized biofilm-induced blockage. The demonstrated biocompatibility, robustness, and scalability of this coating platform underscore its translational potential as a clinically relevant strategy to mitigate HAIs, extend the functional lifetime of medical tubing, and alleviate the global burden of antimicrobial resistance.

Two-dimensional (2D) electronic materials hold immense promise for next-generation bio/neuro-electronic interfaces, but their biocompatibility has remained uncertain due to conflicting reports from studies focused on exfoliated flakes and suspensions. In this work, we present a comprehensive in vitro evaluation of electronic-grade large-area, chemical vapor deposition (CVD)-grown 2D materials - including platinum diselenide (PtSe2), platinum ditelluride (PtTe2), molybdenum disulfide (MoS2), and graphene - as substrates for mouse neural stem cell culture. Across all CVD-grown materials, the stem cells exhibited outstanding viability, with no significant differences in metabolic activity or live/apoptotic cell ratios compared to laminin-coated glass controls (p > 0.05). Importantly, these large-area 2D materials robustly supported neuronal differentiation, as evidenced by widespread {beta}III-tubulin expression. Strikingly, we found that flaky MoS2 promoted significantly greater neuronal maturation (>75% NeuN neurons) than any other substrate tested (25-50% NeuN; p < 0.05), revealing the critical influence of material format on bioactivity. While PtSe2 showed a tendency to promote glial lineage differentiation, our findings firmly establish large-area CVD-grown 2D materials as biocompatible, tunable platforms for neural interfacing, paving the way for their integration into advanced bio/neuro-electronic devices.

Undesired attachment of proteins, cells/bacteria, and organisms on material surfaces is problematic in industrial and health care settings. In this study, polymer coatings are synthesized from subunits of cyclodextrin, an additive/excipient found in food/pharmaceutical formulations. These unique polymers, which have been applied mainly towards sustained drug delivery applications, are evaluated in this study for their ability to mitigate non-specific protein adsorption, mammalian cell (NIH/3T3) adhesion, and bacterial cell (Staphylococcus aureus, Escherichia coli) attachment. Effects of cyclodextrin polymer composition, particularly incorporation of nonpolar crosslinks, on material properties and passive anti-biofouling performance are investigated. Results suggest that lightly-crosslinked cyclodextrin polymers possess excellent passive resistance to protein, cell, and bacterial attachment, likely due to the hydrophilic and electrically neutral surface properties of these coatings. At the same time, anti-biofouling performance decreased with increasing crosslink ratios, possibly a reflection of decreased polymer mobility, increased rigidity, and increased hydrophobic character. Cyclodextrin-based materials may be broadly useful as coatings in industrial or medical applications where biofouling-resistant and/or drug-delivering surfaces are required.

Surface functionalization of biomaterials enables the immobilization of proteins and other molecules and can be utilized to direct the biological response to devices and implants. Fetuin-A is a blood plasma protein involved in numerous physiological processes, including the regulation of mineralization. Notably, many investigations of fetuin-A have explored its cellular interaction when in solution, but limited studies report the role of fetuin-A when used as a surface modifier. The present investigation explores the response elicited by fetuin-A on Saos-2 cells when it is immobilized on a model gold surface through the covalent reaction with dithiobis(succinimdyl propionate) (DSP). Comparative surface characterization using x-ray photoelectron spectroscopy (XPS), atomic force microscopy - infrared spectroscopy (AFM-IR) and surface plasmon resonance (SPR) confirmed the surface modifications but indicate partial inhomogeneity in the functionalizer surface coverage. The interaction of albumin and fetuin-A with the surface was quantified by radiolabeling, quartz crystal microbalance with dissipation (QCM-D) and SPR, demonstrating a higher mass of fetuin-A bound to the surface in comparison to serum albumin. Over 7 days, cells bound to the surfaces with immobilized fetuin-A showed significantly hindered proliferation of osteoblast-like cells compared to the positive control (fibronectin), presumably due to a decrease in cell metabolism. This study provides new insights into the role of fetuin-A in regulating Saos2 cell response and elucidates its potential use in combination with chemical functionalizers for biomedical applications requiring surface modification.

Biomaterials are widely employed across diverse biomedical applications and represent an attractive strategy to explore physiologically how extracellular matrix components influence the cellular response. In this study, we aimed to use previously developed biomimetic streptavidin platforms to investigate the role of glycosaminoglycans (GAGs) in bone morphogenetic protein 2 (BMP2) signaling. However, we observed that the interpretation of our findings was skewed due to the GAG-unrelated, non-specific adsorption of BMP2 on components of our biomaterials. Non-specific adsorption of proteins is a recurrent and challenging issue for biomaterial studies. Despite the initial incorporation of anti-fouling poly(ethylene glycol) (PEG) chains within our biomaterials, the residual non-specific BMP2 adsorption still triggered BMP2 signaling within the same range as our conditions of interest. To tackle this issue, we explored various options to prevent BMP2 non-specific adsorption. Specifically, we tested alternative constructions of our biomaterials on gold or glass substrate using distinct PEG-based linkers. We identified the aggregation of BMP2 at neutral pH as a potential cause of non-specific adsorption and thus determined specific buffer conditions to prevent it. We also investigated the induced BMP2 signaling over different culture periods. Nevertheless, none of these options resulted in a viable suitable solution to reduce the non-specific BMP2 signaling. Next, we studied the effect of various blocking strategies. We identified a blocking condition involving a combination of bovine serum albumin and trehalose that successfully reduced the unspecific attachment of BMP2 and the non-specific signaling. Furthermore, the effect of this blocking step was improved when using gold platforms instead of glass, particularly with Chinese hamster ovary (CHO) cells that seemed less responsive to non-specifically bound BMP2 than C2C12 cells.

Sustainable synthesis of photoluminescent nanomaterials with tuneable surface chemistry and defined biological activity remains a central challenge in green nanoscience. Here we show that the energy-input route used to carbonise a single bearberry (Arctostaphylos uva-ursi) extract precursor system exerts a decisive and mechanistically coherent influence over the surface chemistry, optical performance, and bioactivity of the resulting carbon quantum dots (CQDs). Hydrothermal processing (160 {degrees}C, 6 h) yields particles of 7.13 nm hydrodynamic diameter enriched in surface hydroxyl and carbonyl groups, a higher graphitic sp{superscript 2} carbon fraction (43.06%), and potent DPPH radical scavenging activity. In contrast, microwave-assisted synthesis yields 9.65 nm particles with a higher surface carboxylate content (O-C=O: 19.06%), enhanced fluorescence quantum yield, and increased intracellular uptake. Uptake is statistically significant in retinal epithelial cells at 200 {micro}g/mL (p < 0.001) and shows concentration-dependent accumulation in zebrafish larvae from 100 {micro}g/mL (p < 0.05). Combined XPS C 1s deconvolution and FTIR difference spectroscopy indicate that incomplete decarboxylation under microwave conditions underlies these distinct properties. Both formulations maintained full cytocompatibility across 10-250 {micro}g/mL in both RPE-1 and HeLa cells, with no statistically significant reduction in viability at any tested concentration. These findings define a synthesis-route-encoded structure property relationship that enables rational selection between antioxidant-optimised and imaging-optimised CQD formulations from an identical green precursor system.

Nanomaterials have been extensively investigated for their potential in delivering therapeutics to target tissues, but few have advanced to clinical application. The luminal surface of endothelial cells that line blood vessels are covered by a glycocalyx, a complex extracellular matrix rich in anionic glycans. However, the role of this glycocalyx in governing nanomaterial-cell interactions is often overlooked. In this study, we demonstrate that gold nanoparticles functionalized with branched polyethyleneimine (AuNP+) bind to primary human endothelial cells expressing either a developing or mature glycocalyx, with the interaction involving hyaluronan and heparan sulfate. Notably, the mature glycocalyx decreases the toxicity of AuNP+. In contrast, lipoic acid-functionalized gold nanoparticles (AuNP-) bind to endothelial cells with a developing glycocalyx, but not a mature glycocalyx. To further investigate this phenomenon, we studied charged polymers, including poly(arginine) (polyR) and poly(glutamic acid) (polyE). PolyE does not associate with endothelial cells regardless of glycocalyx maturity, but when glycans are enzymatically degraded, it can bind to the cells. Conversely, polyR associates with endothelial cells irrespective of glycocalyx maturity or glycan degradation. These findings highlight the intricate relationship between nanomaterial charge and presentation in interactions with endothelial cells, offering insights for modulating nanomaterial interactions with the blood vessel wall.

Lifitegrast is an FDA-approved drug that inhibits T-cell mediated inflammation associated with dry eye syndrome (DES). Lifitegrast is a potent inhibitor of the interaction between LFA-1 on T-cells and ICAM-1 on endothelial cells at the ocular surface. While effective in treating DES, 5% (81.2 mM) lifitegrast has low drug utilization and elicits off-target effects. Here we engineer contact lenses to release therapeutically-relevant doses of lifitegrast to every tear film for up to 10-hours. Lifitegrast is coupled to the polymer of the soft hydrogel lens via a photolabile (caged) crosslinker. Exposures of the lens to the 400-430 nm wavelengths of indoor daylight excite the caged crosslinker molecules and trigger a bond-cleavage reaction that releases authentic lifitegrast passively to the tear film. The photoproduct of the reaction remains chemically-linked to the polymer of the single-use lens. Our studies show that passive exposures of the lens to indoor light would generate an average of 990 nM lifitegrast to every tear film in a zero-order reaction for up to 10-hours. This concentration exceeds the Kd for the interaction between ICAM-1 and LFA-1 by [~]330-fold and would sustain inhibition of inflammatory responses at the ocular surface. The amount of lifitegrast released from the lens increases during exposures to outdoor sunlight. Over a 10-hour exposure to indoor light, a single lens would release 0.44% of the lifitegrast present in two drops of commercial 5% lifitegrast. Compared to tear-drop approaches, our engineered lenses would sustain the passive delivery of therapeutically-relevant doses of lifitegrast over a longer period, and exhibit improved drug utilization at a lower cost. Our technology could easily be integrated into daily-use contact lenses in order to prevent inflammation at the ocular surface, dry-eye and contact lens-mediated discomfort. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/439289v1_ufig1.gif" ALT="Figure 1"> View larger version (75K): org.highwire.dtl.DTLVardef@1049076org.highwire.dtl.DTLVardef@a83fceorg.highwire.dtl.DTLVardef@1f52c4borg.highwire.dtl.DTLVardef@12f0ead_HPS_FORMAT_FIGEXP M_FIG C_FIG

The transport of therapeutics and gene carriers to their site of action is often hindered by biological barriers, such as cell layers and basement membranes. Among these, the inner limiting membrane (ILM) represents a major barrier within the eye, separating the vitreous body from the retina. The ILM must be crossed, if for instance gene carriers are to reach retinal target cells following intravitreal administration. However, the ILM is a densely cross-linked basement membrane barrier, allowing only the smallest nanoparticles to pass. Here, we demonstrate that active micro-colloids decorated with enzymes can locally open the ILM and thereby facilitate the diffusion of passive carriers into retinal tissue. We utilize an ex vivo porcine eye model to determine the membrane permeability threshold using fluorescent nanoprobes. We further show that collagenase-decorated silica microparticles can facilitate the transport of nanoparticles, while exhibiting excellent biocompatibility with no adverse morphological or functional retinal effects over a six-week in vivo evaluation in a porcine model. Overall, our findings introduce a biocompatible and minimally invasive strategy to facilitate the targeted nanoparticle transport across biological barriers, which we demonstrate for retinal delivery enabled by active colloids.

Effective tissue regeneration and immune responses are essential for the success of biomaterial implantation. Although the interaction between synthetic materials and biological systems is well-recognized, the role of surface topographical cues in regulating the local osteoimmune microenvironment--specifically, their impact on host tissue and immune cells and their dynamic interactions--remains underexplored. This study addresses this gap by investigating the impact of surface topography on osteogenesis and immunomodulation. We fabricated MXene/Hydroxyapatite (HAP)-coated surfaces with controlled 2.5D nano-, submicro-, and micro-scale topographical patterns using our custom bottom-up pattering method. These engineered surfaces were employed to assess the behavior of osteoblast precursor cells and macrophage polarization. Our results demonstrate that MXene/HAP-coated surfaces with microscale crumpled topography significantly influence osteogenic activity and macrophage polarization: These surfaces notably enhanced osteoblast precursor cell spreading, proliferation, differentiation, and facilitated a shift in macrophages towards an anti-inflammatory, pro-healing M2 phenotype. The observed cell responses indicate that the physical cues from the crumpled topographies, combined with the chemical cues from the MXene/HAP coatings, synergistically create a favorable osteoimmune microenvironment. This study presents the first evidence of employing MXene/HAP-multilayer coated surfaces with finely crumpled topography to concurrently facilitate osteogenesis and immunomodulation for improved implant-to-tissue integration. The tunable topographic patterns of these coatings, coupled with a facile and scalable fabrication process, make them widely applicable for various biomedical purposes. Our results highlight the potential of these novel coatings to improve the in vivo performance and fate of implants by modulating the host response at the material interface.

Antibacterial additive use has surged due to rising incidences of food contamination, despite concerns over antibiotic resistance. Bacteriophage (bacterial viruses) represent a unique and promising opportunity as antibacterial agents, offering targeted bacterial lysis while being food safe. However, their commercial success has been limited by the significant diffusion barriers they face within food, preventing effective delivery at contamination sites. Here, we introduce bacteriophage-loaded microneedle patches that enable targeted phage delivery directly within food, eliminating internal pathogens in a minimally disruptive manner. The application of microneedles within food is first explored. The platform is then substantiated by comparing performance in raw beef and cooked chicken, where we achieved up to 3-logs reduction in Escherichia coli, thus providing complete decontamination according to regulatory limits. In contrast, conventional surface application of the same phage failed to provide significant decontamination. To ensure broad applicability, phage cocktails were also loaded into microneedles to demonstrate polymicrobial decontamination against other common food contaminants including Salmonella. This platform can also be adapted to extend food shelf-life by targeting spoilage-inducing bacteria.

1Self-assembled monolayers (SAMs) have been widely utilized as a way of tailoring surface chemistry through the adsorption of organic molecules to different materials. SAMs are easy to prepare and offer a wide variety of organic molecules that afford additional or improved properties to the coated material. Spatial control of SAM placement has been achieved over many length-scales, even at the nanoscale. However, nanopatterned SAMs are usually prepared through serial processes utilizing atomic scanning probes or soft-lithography utilizing elastomeric masters. These techniques are expensive or not repeatable. Here we present the use of nanospheres for the creation of nanopatterned Au:Cu films which spatially control the grafting of a thermoresponsive SAM made from poly(N-isopropyl acrylamide) (PNIPAM). Chemical characterization validates the presence of PNIPAM and environmental atomic force microscopy showed its response to temperature which was evidenced by a change in stiffness. Our approach represents an affordable large area methodology for repeatable spatial control of SAMs at the nanoscale.

BackgroundMicro- and nanoplastics (MNPs) contamination may pose a significant risk to human health. However, their true impact remains underexplored due to substantial limitations of current analytical methods. Traditional techniques like Raman and FTIR microscopy, coupled with filtration, fail to detect smaller MNPs and are prone to external contamination. Likewise, pyrolysis-GC/MS lacks the ability to pinpoint MNP size or location. MethodsThis study presents a universal approach for MNPs detection in tissues, validated to mitigate external contamination risks and enable the identification of significantly smaller MNPs. The method preserves histological information, allowing for comprehensive spatial analysis, including assesment of local DNA damage using the {gamma}-H2AX histone. FindingsApplying this method to human placenta samples revealed orders of magnitude higher MNP loads than previously reported, with quantities ranging from thousands to millions per cm3, far exceeding current reports of fewer than 1 MNP per gram or cm3 of tissue. Importantly, within the observed concentration range, we found a positive association between MNP load and placental DNA damage. InterpretationOur findings show that that the prevalence of MNPs in biological tissues has been substantially underestimated, as the smallest and potentially most harmful MNPs go undetected with traditional methods. Furthermore, we found that the concentations were linked with genotoxic effects in the placenta. This novel analytical workflow represents a significant advancement in MNPs research and provides crucial insights into their impact on human health. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSPrior to our study, MNPs have been detected in human tissues, including the placenta, but in very low quantities, often fewer than 1 MNP per gram or cm3 (Amereh et al., 2022; Ragusa et al., 2021). Current detection methods, such as Raman and FTIR microscopy, have significant challenges, particularly in detecting MNPs in the lower size range, which are considered more hazardous (Dzier[z]y[n]ski et al., 2024). These methods also involve lengthy sample preparation processes, including chemical dissolution and filtration, which inherently lead to the loss of histological information. Additionally, they carry a high risk of external sample contamination, as well as MNP degradation and alteration, compromising the accuracy and reliability of the results (Renner et al., 2018). Added value of this studyThis study introduces a universal analytical workflow for MNPs detection in tissues that addresses critical limitations of existing methods. By eliminating external contamination risks and enabling the detection of significantly smaller MNPs, this method revealed orders of magnitude higher MNPs loads in human placenta samples compared to previous reports. The preservation of histological information allows for detailed spatial mapping of MNPs, contributing to a more comprehensive understanding of their distribution and potential biological impacts. A key finding of this study is the positive association between MNP load and placental DNA damage, as quantified by {gamma}-H2AX labeling. This direct correlation between MNP exposure and genotoxic effects strongly suggests that the observed DNA damage is not an artifact of external contamination but rather a consequence of internalized MNPs within the tissue. This first finding of the presence of {gamma}-H2AX foci, a well-established biomarker of DNA double-strand breaks, underscores the potential genotoxic risk posed by MNPs and highlights their ability to induce cellular harm at the molecular level. Implications of all the available evidenceOur research indicates that the true MNPs load in human tissues may be significantly higher than previously recognized. The analytical workflow presented here has the potential to transform the field of MNPs research by enabling more accurate assessments of MNP prevalence in human and other biological tissues. Designed with methods and techniques widely available to researchers across disciplines, this workflow can be readily applied to diverse biological and environmental studies. This, in turn, could inform future studies on their biological interactions, long-term health effects, and dose-response relationships. Given the widespread presence of MNPs in the environment, our findings underscore the urgent need for longitudinal studies to evaluate the chronic effects of exposure, particularly in vulnerable populations such as pregnant individuals and their developing fetuses. Additionally, our findings and methodology are a stepping stone towards true direct toxicological research on MNPs. Addressing MNP contamination at the source and improving public and regulatory awareness are critical steps toward developing effective mitigation strategies.

Infections are a significant risk to patients who receive medical implants, and can often lead to implant failure, tissue necrosis, and even amputation. So far, although various surface modification approaches have been proposed for prevention and treatment of microbial biofilms on indwelling medical devices, most are too expensive/complicated to fabricate, unscalable, or limited in durability for clinical use. Here we present a new bottom-up design for fabricating scalable and durable nano-pattered coatings with dynamic topography for long-term antibacterial effects. We show that MXene layer-by-layer (LbL) self-assembled coatings -- with finely tunable crumple structures with nanometer resolution and excellent mechanical durability -- can be successfully fabricated on stretchable poly(dimethylsiloxane) (PDMS). The crumpled MXene coating with sharp-edged peaks shows potent antibacterial effects against Staphylococcus aureus and Escherichia coli. In addition, we find that on-demand dynamic deformation of the crumpled coating can remove [&ge;]99% of adhered bacterial cells for both species, resulting in a clean surface with restored functionality. This approach offers improved practicality, scalability, and antibacterial durability over previous methods, and its flexibility may lend itself to many types of biomaterials and implantable devices.

The development of an effective for subcutaneous or intradermal injection drug delivery requires systems with improved bioavailability and biocompatibility. Systematic physicochemical and biological interrogation of carnauba-wax/red-palm-oil lipid nanoparticles (LNPs) stabilised with d--tocopheryl-PEG-1000-succinate and polysorbate-40 shows that purposeful matrix engineering yields a robust sub-50 nm carrier for under-skin delivery. Cryo-TEM and SAXS uncover a disc-toroid hybrid morphology dominated by 30-40 nm particles with toroidal/disc shape - an advantageous biconcave geometry to enhance surface-to-volume ratio and is expected to accelerate enzymatic erosion after injection. Orthogonal analytics (AF4-MD, DLS, MALS, WAXS) confirmed that loading with quinine or dihydroartemisinin leaves size and crystallinity unchanged while delivering encapsulation efficiencies of approximately 90 % and long-term particle stability up to 18 months at 4 {degrees}C. Red-palm oil and the dual-surfactant corona act synergistically to suppress bimodality and narrow size distribution compared with single-component controls. Short-term viability assays in keratinocytes, fibroblasts and macrophages showed no cytotoxicity even at [&ge;]1 % (w/v) lipid, underscoring excellent biocompatibility. Fluorescein-labelled LNPs injected into ex vivo human skin traversed the dermis and hypodermis, while only nanomolar lipid concentrations appeared in the receiver medium, indicating a sustained local depot. Collectively, these insights link composition, structure and performance, positioning wax-based disc-toroid LNPs as a flexible platform for high-load delivery of small-molecule or biopharmaceutical therapeutics via minimally invasive under-skin administration.

Red-emitting carbon quantum dots (HP-CQDs) were synthesised for the first time from aqueous leaf extracts of Hamelia patens through single-step, reagent-free microwave-assisted carbonisation (750 W). The resulting nanoparticles displayed a narrow hydrodynamic size distribution centred at 3.9 nm, consistent with atomic force microscopy measurements showing a maximum height of 2.81 nm. Under 400 nm excitation, the CQDs exhibited a characteristic red emission maximum at 675 nm, representing a rare example of long-wavelength-emitting green CQDs derived from plant biomass. UV-Vis absorption bands at 224 and 256 nm were assigned to {pi}-{pi}* transitions of aromatic carbon domains and n-{pi}* transitions associated with carbonyl-containing surface groups, respectively. X-ray photoelectron spectroscopy (XPS) indicated a carbon-rich composition (C: 67.24%, O: 31.25%, N: 1.52%) with prominent C-O (42.67%) and C-C/C=C (42.64%) contributions. ATR-FTIR further confirmed the retention of hydroxyl, ether, and aliphatic functionalities following carbonisation. The excitation-wavelength-independent emission peak position implicates discrete surface molecular states rather than a heterogeneous distribution of emitters. HP-CQDs exhibit potent DPPH radical scavenging activity (IC50 = 141.8 {micro}g mL-1), comparable to ascorbic acid (IC50 = 114.8 {micro}g mL-1), and maintain >95% cell viability in both HeLa and RPE-1 cells up to 250 {micro}g mL-1. Confocal microscopy demonstrates concentration-dependent cytoplasmic accumulation and selective perinuclear localization at 300 {micro}g mL-1. In vivo biodistribution in zebrafish larvae confirms systemic uptake with statistically significant fluorescence enhancement at 500 {micro}g mL-1 (p < 0.01), establishing HP-CQDs as biocompatible red-fluorescent probes with dual imaging-antioxidant functionality. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/724069v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@1dbe864org.highwire.dtl.DTLVardef@763ed0org.highwire.dtl.DTLVardef@115e9b9org.highwire.dtl.DTLVardef@1a3941e_HPS_FORMAT_FIGEXP M_FIG C_FIG

Nanoscale-based tools for immunomodulation are expected to offer a rich battery of options for more targeted and safer approaches to achieve clinically effective manipulation of the local and systemic immune environment. In this study, we aimed to design nanoscale constructs based on graphene oxide (GO) nanosheets as platform carriers for the TLR7/8 agonist Resiquimod (R848). The non-covalent complexation of R848 molecules on the GO surface resulted in stable complexes by preserving their biological activity. The physicochemical properties, molecular quantification, as well as the overall performance of the complex were systematically investigated. We hypothesized the formation of GO:drug nano-constructs with strong colloidal stability over time, due to the strong {pi}-{pi} interactions between the R848 molecules and the GO surface, and identified that R848 loading efficiency consistently ranged around 75% (of starting molecules), quantified by HPLC and UV-Vis. The 2D morphology of the thin nanosheets was retained after complexation, determined by various (AFM and SEM) microscopic techniques. Based on the surface physicochemical characterization of the complexes by Raman, FTIR, XPS, and XRD, the formation of non-covalent interactions among the GO surface and the R848 molecules was confirmed. Most importantly, GO:R848 complexes did not compromise the biological activity of R848, and effectively activated macrophages in vitro. Collectively, this study demonstrates that thin GO sheets can act as platforms for the non-covalent association with small TLR7/8 agonist molecules, forming stable and highly reproducible complexes, that could be exploited as effective immunomodulatory agents.

Wound and device-associated infections remain difficult to eradicate because biofilms block host immunity and antibiotics, accelerating chronicity and resistance. Here, we present a portable, low-cost dual-syringe spray that deposits an ultra-thin, self-assembling antimicrobial film directly on wounds and implant surfaces. The device co-delivers oppositely charged hyaluronic acid (HA) and a cationic antimicrobial peptide (polyarginine, PAR30), which rapidly form a conformal nanometric polyelectrolyte complex at the tissue-material interface. Molecular dynamics simulation revealed pronounced positional heterogeneity within the PAR30/HA complex and identified an N-terminal arginine as a dominant interaction hotspot. The resulting coating adheres to diverse substrates, kills bacteria on contact, prevents biofilm formation, and sustains antimicrobial efficacy. Across vitro assays and murine wound infection models, treatment produced 4 to 5 log reductions in bacterial burden against methicillin-resistant Staphylococcus aureus and Gram-negative pathogens, including Pseudomonas aeruginosa and Escherichia coli. The formulation is biocompatible, did not increase cutaneous inflammation or IL-6 levels in vivo, and reduced post-surgical pain and motor deficits in a mouse incision model. To our knowledge, this is the first antimicrobial treatment system applicable to both tissues and medical devices. Developed under a safe-and-sustainable-by-design approach, this technology combines biocompatible components, nanometric coating for minimal material use, and a simple syringe-based delivery device, offering a scalable, antibiotic-free strategy for wound care and medical device infection prevention. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=173 HEIGHT=200 SRC="FIGDIR/small/717441v1_ufig1.gif" ALT="Figure 1"> View larger version (68K): org.highwire.dtl.DTLVardef@49381aorg.highwire.dtl.DTLVardef@1023e64org.highwire.dtl.DTLVardef@4e282aorg.highwire.dtl.DTLVardef@12eeae4_HPS_FORMAT_FIGEXP M_FIG C_FIG

The scalable fabrication of stable colloidosomes with controlled permeability and defined multicompartmental architecture remains a critical challenge, limiting their broader use in molecular delivery and environmental remediation. Here, we develop a hybrid lipid-metal-organic framework (lipid-MOF) colloidosome assembled through an interfacial emulsification strategy that integrates the structural rigidity of ZIF-8 particles with lipid-mediated membrane stabilization. During assembly, ZIF-8 particles accumulate at the oil-water interface to form a shell, producing hollow micron-sized spherical colloidosomes. The resulting colloidosomes exhibit excellent colloidal stability in aqueous media for over 30 days with a zeta potential of approximately -50 mV. Nitrogen adsorption measurements reveal a surface area of 45 m2g-1 and an average pore width of 4 nm. Fluorescence imaging shows that hydrophobic Nile red preferentially partitions into the colloidosomal membrane, whereas hydrophilic fluorescein isothiocyanate (FITC) localize predominantly within the aqueous interior, enabling simultaneous encapsulation of molecules with contrasting polarity with loading efficiencies approaching 90%. Furthermore, the colloidosomes demonstrate rapid removal of model pollutants from water, achieving >90% removal of methylene blue and metal ions without stirring. Together, these results introduce lipid-MOF colloidosomes as a new class of hybrid platforms that unify structural stability, multicompartmental encapsulation, and efficient adsorption behavior, opening pathways toward sustainable platforms for drug delivery and environmental bioremediation.