Copper oxide (CuO) and Mg-doped CuO (CuO-Mg) nanoparticles were synthesized using a green approach with Azadirachta indica leaf extract. The biosynthesized nanoparticles were characterized using multiple techniques including x-ray diffraction (XRD), energy-dispersive x-ray (EDX) analysis, scanning electron microscopy (SEM), and UV-Vis-NIR spectrometry. The XRD analysis verified the purity of the synthesized materials and confirmed a monoclinic crystal structure. Doping CuO with Mg decreased the average crystallite size. EDX spectral analysis confirmed the presence of Cu, Mg, and O elements in the Mg-doped nanoparticles. The optical bandgap ranged from 1.28 to 1.37 eV, in which undoped CuO exhibited a high optical bandgap. The antibacterial activity of CuO nanoparticles increased upon increasing the concentration of Mg doping against the tested pathogens, including Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Staphylococcus aureus. The biosynthesized CuO and Mg-doped CuO nanoparticles demonstrated potent concentration-dependent cytotoxic effects on breast cancer cells, achieving complete growth inhibition at 70 μg/ml CuO and 60 μg/ml Mg-doped CuO, with IC50 values of approximately 35.4 and 30.0 μg/ml, respectively.
Polycaprolactone (PCL) has emerged as a promising biomaterial for artificial heart applications due to its biodegradability and mechanical properties. However, its hydrophobic nature and limited biocompatibility pose challenges for cardiovascular applications, requiring optimal cell-material interactions. This study investigates the surface modification of silk fibroin-derived peptide/PCL coatings to enhance biocompatibility and cellular response for potential artificial heart applications. PCL substrates were blended with varying concentrations of silk fibroin-derived peptide (0.2%, 0.5%, and 1% w/v). Surface characterization was performed using water contact angle measurements, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy. Biocompatibility was evaluated through cell viability assays and CD31 expression analysis. Silk fibroin-derived peptide incorporation significantly improved surface hydrophilicity, with contact angles decreasing from 78° (bare PCL) to 62° (1% silk fibroin-derived peptide). FTIR analysis confirmed successful incorporation of silk fibroin-derived peptides, showing characteristic PCL ester C=O absorption at ∼1720 cm-1 and concentration-dependent amide I contributions at ∼1630-1670 cm-1. Cell viability studies demonstrated enhanced cellular response with increasing silk fibroin-derived peptide concentration, particularly evident at day 7. CD31 expression analysis revealed improved endothelial marker expression, with the highest levels observed on 1% silk fibroin-derived peptide-incorporated substrates. The results demonstrate that silk fibroin blended to PCL significantly enhances biocompatibility through improved hydrophilicity and cellular interactions. Taken together, these preliminary results indicate that silk fibroin-derived peptide-incorporated PCL could represent a promising biomaterial platform for artificial heart applications, with the potential to improve endothelial compatibility and support endothelialization.
This study examines sulfamethoxazole (SMX), a sulfonamide antibiotic strongly associated with severe cutaneous adverse effects, as a potential regulator of invariant natural killer T (iNKT) cells. This work combines molecular docking (to evaluate the likelihood of SMX binding to residues within a conventional binding pocket), molecular dynamics (to assess the stability of SMX binding and the forces that may destabilize the interaction), flow cytometry (to evaluate iNKT-cell activation in the presence of SMX within the context of established antigen presentation models), and particularly Raman spectroscopy (to investigate whether SMX-associated spectral features are retained after co-incubation and interaction) directly on sorted iNKT cells. Functional activation was assessed through IFN-γ production from sorted iNKT cells and correlated with Raman spectral data to support our hypothesis. The Raman spectroscopy was performed on both CD1d dimer (in isolation) as the presenter molecule of the drug and in sorted iNKT cells (in isolation), to identify spectroscopic evidence of drug-CD1dimer or drug-cell interactions under near-physiological conditions. From the CD1d experiment, we observed spectral features consistent with potential interactions between CD1d and serum-derived lipids, in a manner comparable to the positive control (α-GalCer). From the iNKT experiment, peaks at 1610 and 1663 cm-1 are the representative peaks that emerge under SMX stimulation conditions in iNKT cells (through TCR binding), as identified by second principal component (PC2) analysis. From the complete experiment, (CD1d + iNKT) suggests the possibility of a direct interaction between SMX and iNKT TCRs. Flow cytometry analysis further demonstrated a significant increase in ZAP-70 phosphorylation in sorted iNKT cells exposed to SMX under serum-free conditions, supporting the possibility of proximal TCR-associated signaling in the absence of CD1d.
Foliar fungal diseases are major threats to global grain production, which is integral to food security and agricultural economies. Current management relies on broadacre fungicides applied after infection, which are costly, environmentally problematic, and promote the emergence of chemically resilient phytopathogens. Prophylactic strategies remain limited, but a shared requirement of foliar disease may be a key target for intervention: the pathogen must successfully detect and recognize the surface of their host. The initial point of contact in plant-fungi interactions can hence be reframed as a biointerface problem governed by the physicochemical properties of the leaf surface. Leaf surfaces are coated in a waxy layer called the cuticle, a biocomposite comprised of a cutin matrix embedded and coated with compounds called cuticular waxes. Increasing evidence shows that these waxes can signal recognition to pathogenic fungi to promote infection. However, studying these interactions is challenging due to their complexity, with whole-leaf models masking the contributions of individual surface variables. To address this, we propose a biomimetic model system using fabricated wax films to replicate native leaf chemistries on inert substrates. These systems allow for precise tuning of surface physicochemical properties, enabling systematic investigation of fungal responses to defined surface chemistries. These systems can then be used to develop prophylactic strategies that alter leaf surface properties, disrupting host-recognition in fungal pathogens to reduce foliar fungal disease incidence in agriculture globally. By reframing fungal disease as a biointerface problem, this research offers a path toward more sustainable and targeted fungal disease management.
Hydrogels are high-water-content polymer networks similar to those of soft tissues and have shown immense potential in fields such as tissue engineering, flexible electronics, and intelligent sensors. However, traditional hydrogels still face challenges such as low mechanical strength, poor toughness, and susceptibility to fatigue. Inspired by tough natural soft tissues (such as muscles and tendons), the introduction of a robust fibrous network into hydrogels enables effective stress transfer, crack bridging, and energy dissipation, thus overcoming the mechanical limitations of traditional hydrogels. This paper reviews fiber-reinforced hydrogels prepared from different reinforcing fibers (e.g., natural, synthetic, inorganic, and carbon-based), as well as the interfacial interactions between the fibers and the matrix (including physical entanglement, dynamic noncovalent bonds, and covalent bonds), and summarizes the preparation methods, such as in situ infiltration, directional freezing, and 3D printing. It also discusses their applications in the fields of medicine, sensing, and wearable devices and finally provides an outlook on current challenges such as precise interface regulation and large-scale intelligent manufacturing.
Real-time monitoring of biological barrier integrity is crucial for drug development and disease modeling. The gold-standard technique, transendothelial electrical resistance (TEER), is often limited by the cost and complexity of commercial alternating current systems. To address this, we developed a novel, low-cost biosensor based on a direct current (DC) series voltage division principle, featuring custom hardware and open-source firmware. Validation demonstrated a wide dynamic range (155-105 600 Ω cm2) and high accuracy (±3%). The device showed excellent correlation with a commercial EVOM3 system in monitoring TEER trends during endothelial barrier formation and oxidative stress-induced disruption. Biosensor readings were consistent with barrier kinetics captured by xCelligence RTCA and live-cell imaging. Furthermore, a strong negative correlation was established between decreasing TEER values and increasing paracellular leakage of sodium fluorescein. These results collectively validate our DC-based system as a reliable, accurate, and accessible tool for quantifying in vitro barrier integrity, with significant potential to democratize research in biomedicine and toxicology.
This Special Topic Collection brings together a diverse and timely collection of contributions that reflect the expanding frontiers of biointerfaces research in India. We are deeply grateful to all the authors for their contributions. This collection explores themes that are both fundamental in scope and closely aligned with pressing biomedical challenges, including cancer metastasis, drug delivery, genetic disorders, and biomaterials design. We briefly highlight the key findings in each of the contributions that make up this collection.
Efficient illumination and light management are increasingly important in modern society. Biomimetic strategies inspired by biological optical systems have, therefore, attracted considerable attention for the development of novel photonic devices. This study investigates light control mechanisms in the photophores of the bioluminescent deep-sea bristlemouth Sigmops gracilis (Gonostomatidae). The reflection and scattering properties of photophores were examined under external illumination. Strong light scattering from guanine platelets was observed on the photophore surface. The observed scattering behavior was successfully reproduced using a biomimetic model consisting of multiple aligned thin chambers containing guanine platelets suspended in water, demonstrating that multilayered platelet assemblies significantly enhance reflectivity. These results indicate that the accumulation of guanine platelets at the photophore surface contributes to increased light intensity around the photophore. In addition, guanine platelets exhibiting anisotropic directional scattering, similar to that observed on the fish body surface, were reconstructed using a magnetic rotation method. Together with previous findings on internal photophore components, these results suggest that external photophore structures in bioluminescent deep-sea fish provide an effective biomimetic strategy for the efficient reuse and redirection of light emitted from photocytes.
Specialized bacteria can effectively nucleate ice crystals using ice nucleating proteins (INPs) anchored to the cell surface. Biogenic freezing has several applications, from snow making to cryo-medicine and freeze/antifreeze materials. For biomimetic designs of INP analogs, it is important to understand how the proteins involved in the process bind to material surfaces. In this study, we determine the binding of a model INP to hydrophobic self-assembled monolayers (SAMs) as well as hydrophilic carboxyl-terminated SAMs. INPs are large proteins with more than 1200 amino acids and a long series of repeat units. Since full-length INPs are difficult to produce and handle, we have investigated a shorter model INP dubbed InaZ9R, which has nine repeat units and still folds into the hallmark beta-helix structure known from the full-length protein. Combining x-ray photoelectron spectroscopy and near-edge x-ray absorption fine structure spectroscopy, we find that InaZ9R form closely packed monolayers on both hydrophilic and hydrophobic surfaces. Angle-resolved nitrogen K-edge near-edge x-ray absorption fine structure spectra show a high degree of orientational order associated with the native β-sheet structure.
Ant middens represent accumulations of discarded materials and provide insight into colony-level foraging and processing behavior. While middens of granivorous ants are typically dominated by plant material, animal remains are occasionally present, yet their origin and mechanical basis remain poorly understood. Here, we investigated the occurrence of gastropod shells in an external midden of the harvester ant Messor wasmanni and evaluated ant mandible mechanics to provide some background for shell fracturing. Midden material was collected during three sampling events and sorted by material type and size. Snail shells were identified to either genus or species level, fracture locations were documented, and representative shells were fractured experimentally using major worker mandibles to quantify shell-breaking forces. The forces varied widely depending on snail species, growth stage, and fracture location, with juvenile shells and mechanically weak regions fracturing at substantially lower forces than adult shells or their reinforced regions. Nanoindentation revealed strong regional and caste-specific differences in mandible mechanical properties, with highest hardness and Young's modulus at the masticatory margin of major workers. Elemental analyses showed enrichment of zinc and other metals in cutting edges, consistent with enhanced wear resistance. This study integrates ecological, mechanical, and material data to provide a mechanistic framework for interpreting snail shell occurrence in ant middens.
Biliary stents are medical devices inserted into the bile duct to treat biliary strictures. However, inserted stents can become occluded within a few months after placement. In this study, the inner surface of a polyethylene (PE) tube was plasma-treated with helium (He), nitrogen (N2), oxygen (O2), and their gas mixtures to improve resistance to stent occlusion. Surface characteristics were analyzed by water contact angle (WCA) and x-ray photoelectron spectroscopy (XPS) measurements. In the WCA results, bare PE without plasma treatment was the most hydrophobic at 100.7°, whereas PE(He) plasma-treated with He gas became the most hydrophilic at 26.1°. XPS deconvolution analysis revealed that the PE(He) and PE(He/N2) contained a considerable proportion of O 1s present as amide (-CONH-) groups exceeding 40%, whereas the other samples had proportions below 7%. The resistance to stent occlusion was verified through microbial and cancer cell adhesion assays. In the microbial adhesion assay, Escherichia coli (E. coli) was used, and PE(He) showed a statistically significant reduction in E. coli growth compared to bare PE. Inhibition of cancer cell adhesion was the most pronounced in PE(He) and PE(He/N2), with reductions in fluorescence intensities of 75.5% and 81.5%, respectively. Overall, both surface hydrophilization and amidation were found to be effective in inhibiting the adhesion of organic contaminants. It was proposed that plasma surface treatment has the potential to improve resistance to biliary stent occlusion.
The Langmuir monolayer technique has proven to be an effective method for constructing lipid-based models of cell membranes. Compared to other artificial membrane systems, such as liposomes or supported lipid bilayers, it offers a relatively simple and versatile approach to reconstructing lipid components of biological membranes and systematically modifying their composition. The technique allows precise control over experimental parameters such as surface pressure and temperature, which influence the physical state and organization of lipid monolayers. Lipid monolayer models are widely used to investigate molecular interactions at membrane interfaces, including the effects of biomolecules or xenobiotics on membrane properties, identification of potential molecular targets of drugs, and evaluation of mechanisms underlying their pharmacological activity or toxicity. While the successful application of the monolayer technique in lipid membrane modeling has been extensively reported in the literature, comprehensive discussions of lipid compositions for modeling various membrane types-such as eukaryotic, prokaryotic, viral, and pathological membranes-remain limited. In particular, systematic descriptions of lipid mixtures used to model membranes characteristic of eukaryotic cells, prokaryotes, viruses, or pathological states are limited. The aim of this review is to address this gap by summarizing lipid compositions used in Langmuir monolayer models designed to mimic different biological membrane types.
As the body's largest organ and primary protective barrier, skin is critical for maintaining physiological homeostasis. Severe skin injuries pose a major global healthcare challenge, with hundreds of thousands of annual deaths attributed to limited transplantable skin availability. 3D bioprinting has emerged as a revolutionary approach to fabricate biomimetic, anatomically precise skin constructs. This review summarizes the research progress of 3D bioprinting in skin structural and functional regeneration: it systematically assesses five core bioprinting technologies (extrusion, inkjet, stereolithography, laser-induced forward transfer, and in situ printing) along with their advantages and limitations in skin fabrication; outlines advancements in skin-specific bioinks (biomaterials, skin cells, growth factors and medicines) and their regulatory roles in regeneration; and discusses achievements and challenges in reconstructing skin vasculature, and pigmentation. Finally, current bottlenecks and future directions for achieving complete structural and functional skin regeneration via 3D bioprinting are comprehensively addressed.
Mollusks, and their particularly diverse class Gastropoda, owe much of their ecological success due to the evolution of their radula-a specialized feeding apparatus. This structure, composed of a chitinous membrane and sometimes mineralized teeth, plays a critical role in food acquisition and processing across a wide range of habitats. The radula's morphology, material composition, and mechanical properties exhibit remarkable diversity and functional optimization, shaped by millions of years of evolutionary refinement. Adaptive variations in tooth shape, composite material content (often rich in iron, calcium, silicon, or other elements), mechanical properties, and coordinated interaction among radular components enable mollusks to withstand strong contact forces, minimize structural failure and tooth wear, and thrive in distinct ecological niches. This review synthesizes current insights into the structure and mechanical properties of the radula teeth, highlighting its adaptations to the preferred ingesta and the functional principles of the teeth. In the course of adaptation to similar physical constraints of the ingesta, different solutions evolved independently. Besides main aspects interesting for ecological research and organismic biology, the radula's structural intelligence and efficiency present a rich source of inspiration for biomimetic innovation.
Lyme disease, caused by the bacterium Borrelia burgdorferi (B. burgdorferi), is a significant public health concern in North America, with approximately 500 000 cases reported annually in the United States. The dissemination of B. burgdorferi from the initial tick bite site to various tissues is facilitated by surface adhesins that bind to extracellular matrix proteins such as fibronectin (Fn). This study investigates the binding dynamics of B. burgdorferi surface proteins RevA, BBK32, BmpA, OspA, FlaB, and OspC to Fn using atomic force microscopy-based single-molecule force spectroscopy. Our results demonstrate that RevA and BBK32 form strong, stable bonds with Fn, highlighting their roles as key mediators of host-cell attachment. By quantifying the rupture forces and kinetic parameters of these interactions, we provide a deeper understanding of B. burgdorferi adhesion mechanics and offer insights into potential therapeutic strategies targeting early bacterial attachment.
Vapor-deposited polymer films offer a solvent-free, scalable route to engineer optically functional biointerfaces with tunable geometry. Recently developed technologies, such as condensed droplet polymerization (CDP), enable the direct fabrication of polymer dome arrays (PDAs) with precise control over size, curvature, and array density, as key parameters for high-resolution imaging and cellular compatibility. This perspective highlights the unique advantages of CDP-based microlenses as solid immersion lenses for live-cell imaging, pointing to their potential integration into tissue scaffolds, point-of-care diagnostics, and drug delivery platforms. We further discuss how polymeric material selection could enable refractive index tuning, mechanical adaptability, and biocompatibility for diverse biological applications. These capabilities position CDP-fabricated microlenses as a multifunctional platform for high-resolution imaging and for exploring how precisely engineered surface curvatures influence curvature-mediated signaling, mechano-transduction, and intracellular communication.
Bacterial strains can be divided into pathogenic and nonpathogenic strains. Distinguishing between the characteristics of these two types will help us understand the mechanisms that bacteria use to cause infections. Thus, the differences in the adhesion to a model hydrophilic silicon nitride surface and in the conformational properties between pathogenic and nonpathogenic Listeria species were probed using atomic force microscopy (AFM). The AFM force-distance approach curves were fitted to two steric models, the steric model and the extended-steric model, which assume the presence of one or two brushes on the bacterial cell surface, respectively. Our results indicated that no significant differences were noticed in the mean adhesion forces measured for pathogenic and nonpathogenic strains using the silicon nitride model surface. However, a larger number of adhesion peaks was found in the AFM retraction curves of the pathogenic strains. Similarly, when the conformational properties, represented by the mean thickness and the mean grafting density of the biopolymer brush, were determined using the steric model, no significant differences were observed between the pathogenic and nonpathogenic strains. However, when the conformational properties, represented by the mean thickness and the mean grafting density of the two brush layers, were quantified using the extended-steric model, it was found that the pathogenic strains had a lower mean grafting density for the first long brush and a higher mean grafting density for the second short brush. Thus, our findings demonstrate that the extended-steric model provides a more detailed view of the conformational properties of Gram-positive Listeria strains and allows for the detection of existing differences.
Hydrolytic and enzymatic degradation of linear segmented polyurethanes with differing compositions were studied by atomic force microscopy and time-of-flight secondary ion mass spectroscopy. Poly (ester urethane urea)s (PEUUs) with two different molecular ratios of polycaprolactone diol (PCL) soft segments and L-lysine diisocyanate/hydrazine hard segments were exposed to aqueous conditions (water or phosphate buffered saline), and the changes in their surface chemistry and morphology were studied. It was found that polymer surface roughness in aqueous conditions is significantly affected by its bulk composition. After soaking in an aqueous buffer solution, the surface of PEUU with higher PCL concentration became significantly rougher compared to PEUU with lower PCL concentration. This surface roughening can be attributed to PCL lost from the surface during hydrolytic degradation. Despite the surface roughness changes, the rate of the hydrolytic degradation of PEUUs was found to be independent of bulk polymer composition. Enzymatic degradation of a linear segmented PEUU containing an oligopeptide segment [poly(peptide urethane urea) (PPUU)] in a collagenase solution was also investigated. The PPUU oligopeptide segment contained proline, hydroxyproline, and glycine amino acids. In a collagenase solution, the PPUU polymer exhibited a significantly higher degradation rate and surface roughness compared to a PEUU polymer that did not contain the oligopeptide segment.
High-speed atomic force microscopy (HS-AFM) was used to directly visualize the single-molecule adsorption dynamics of fibrinogen (FG) and bovine serum albumin (BSA) on atomically smooth mica and on silica nanoparticle (SiNP) coatings. By capturing the motion of individual proteins against a static background, HS-AFM enables the resolution of key dynamic processes, including surface diffusion, conformational adaptation, binding and unbinding events, and interfacial fluctuations on nanostructured surfaces. The results revealed two distinct, protein-specific adsorption mechanisms on SiNP coatings. BSA adsorbed via strong protein-surface interactions that promoted conformational adaptation and localized shell-like coverage of individual nanoparticles-progressively occupying interparticle interstices but leaving the overall nanoparticle topography visible. In contrast, FG adsorption followed a concentration-dependent, two-stage process; proteins first adsorbing directly to the nanoparticle surface, and at higher coverages, associated via protein-protein interactions, producing a secondary, dynamic, and loosely bound outer layer. This FG protein layer reduced the root-mean-square roughness of the underlying surface from a peak of ∼13.2 to ∼7.8 nm while introducing pronounced molecular-level fluctuations at the interface, as inferred from tip-induced smearing in HS-AFM images. These findings demonstrate that the relevant biological interface is not a static substrate, but a dynamic, structurally defined protein layer, whose properties are dictated by both nanoscale surface topography and the characteristics of the adsorbing proteins.
We aimed to synthesize modified magnesium nanowire (Ti-NW-Mg) on the surface of titanium implants and to investigate its effects on bone binding by regulating macrophage polarization in vitro. The Ti-NW-Mg was synthesized from smooth titanium (CP-Ti) by hydrofluoric acid etching and high temperature alkalization, and then through the displacement reaction of magnesium sulfate solution with the titanium surface. The control groups were CP-Ti, sandblasted and etched with acid titanium (Ti-SLA), and only for micro/nano-modified titanium surfaces (Ti-NW). The physicochemical properties of the Ti-NW-Mg surface were examined. The biological effects of materials on RAW264.7 cells were compared, and the effects on osteogenesis by mediating RAW264.7 polarization were discussed. We observed the effect of the materials on osteogenesis through immunohistochemistry. In this experiment, the Ti-NW-Mg surface was interwoven into a nanotopological network, which released a specific concentration of magnesium ions and had good hydrophilicity. Compared to CP-Ti, Ti-SLA, and Ti-NW, Ti-NW-Mg reduced the proliferation of macrophages on the surface, inhibited inflammation, regulated macrophage polarization, and promoted bone formation. Ti-NW-Mg reduced the proliferation and adhesion of macrophages and decreased the release of inflammatory factors from macrophages. These results provide an essential experimental basis for the effect of Ti-NW-Mg on improving implant osteogenesis and increasing the implant success rate.
