Initial Adhesion Research Articles

PREPRINT Machine Learning for the Sensitivity Analysis of a Model of the Cellular Uptake of Nanoparticles for the Treatment of Cancer.

Experimental studies on the cellular uptake of nanoparticles (NPs), useful for the investigation of NP-based drug delivery systems, are often difficult to interpret due to the large number of parameters that can contribute to the phenomenon. It is therefore of great interest to identify insignificant parameters to reduce the number of variables used for the design of experiments. In this work, a model of the wrapping of elliptical NPs by the cell membrane is used to compare the influence of the aspect ratio of the NP, the membrane tension, the NP-membrane adhesion, and its variation during the interaction with the NP on the equilibrium state of the wrapping process. Several surrogate models, such as Kriging, Polynomial Chaos Expansion (PCE), and artificial neural networks (ANN) have been built and compared to emulate the computationally expensive model. Only the ANN-based model outperformed the other approaches by providing much better predictivity metrics and could therefore be used to compute the sensitivity indices. Our results showed that the NP's aspect ratio, the initial NP-membrane adhesion, the membrane tension, and the delay for the increase of the NP-membrane adhesion after receptor dynamics are the main contributors to the cellular internalization of the NP, while the influence of other parameters is negligible.

Simulation study on mitigating permeate flux decline with electroosmotic flux in dead-end ultrafiltration process

Piezoelectric membranes establish electrokinetic phenomena, including electroosmotic flow, to mitigate membrane fouling in the ultrafiltration process. This study employs numerical simulations to evaluate the role and impact of the electroosmotic flux effect on permeate flux decline and fouling mechanisms in the dead-end filtration process for silicon dioxide particles. This research demonstrates that electroosmotic flux significantly alleviates flux decline across varying values of surface zeta potential, membrane porosity, particle size and inlet concentration. Specifically, the electroosmotic flux effect is most pronounced in reducing flux decline when the surface zeta potential is higher and the membrane structure is more porous. This reduction in flux decline is attributed to the enhanced lift and drag forces generated by electroosmotic flux near the electrical double layer, which prevents rapid initial adhesion and subsequent fouling, such as internal blocking and cake layer formation. Additionally, the electroosmotic flux effect is most effective with smaller particle sizes and higher feed concentrations, helping to mitigate flux decline that would otherwise occur in the absence of electroosmotic flux. Compared to experimental and modelling investigations, the electroosmotic flux effect is shown to complement a reduction in permeate flux drop to facilitate the longevity of membranes in the ultrafiltration process.

Kanamycin promotes biofilm viability of MRSA strains showing extremely high resistance to kanamycin

Staphylococcus aureus is widely distributed in environment and can cause various human infection and food poisoning cases. Also, this pathogen is a typical biofilm former, which further complicates its pathogenicity. Antibiotics have been widely used to eliminate pathogenic bacteria, but their indiscriminate use has also led to the widespread emergence of drug-resistant bacteria, such as Methicillin-Resistant Staphylococcus aureus (MRSA). In this study, the effect of antibiotics on biofilm formation of MRSA strains 875 and 184 was explored. Firstly, MRSA 875 belongs to SCCmec type IV, ST239, carrying the atl, icaA, icaD, icaBC, and aap genes, and MRSA 184 belongs to SCCmec type II, ST5, carrying the atl, icaD, icaBC, aap, and agr genes. Then, a total of 8 antibiotics have been selected, including kanamycin, gentamycin, cipprofloxacin, erythromycin, meropenem, penicillin G, tetracycline, vancomycin. Minimum inhibitory concentrations (MICs) of each antibiotic were determined, and MIC of MRSA 875 and 184 to kanamycin/gentamicin are 2048/64 μg/mL and 2048/4 μg/mL, respectively. A total of 10 concentrations, ranging from 1/128 to 4 MIC with 2-fold, were used to study biofilm formation. Biofilm biomass and viability were determined during different phases, including initial adhesion (8 h), proliferation (16 h), accumulation (24 h) and maturation (48 h). Importantly, kanamycin at specific concentrations showed significant promotion of biofilm biomass and biofilm viability, with none of such observation acquired from other antibiotics. This study provides scientific basis and new research ideas for the quality control technology of microorganisms and safety prevention of MRSA.

Nanoscale Strategies for Enhancing the Performance of Adhesive Dry Electrodes for the Skin.

High-quality electrophysiological monitoring requires electrodes to maintain a compliant and stable skin contact. This necessitates low impedance, good skin compliance, and strong adhesion to ensure continuous and stable contact under dynamic conditions. In this context, adhesive epidermal dry electrodes are advancing rapidly, which is promising for long-term applications in clinical diagnosis, wearable health monitoring, and human-machine interfaces. However, challenges persist, as conventional technologies usually fall short of meeting the high standards required for electrophysiological electrodes. This Perspective discusses four key aspects for high-performance epidermal electrodes from an adhesive perspective: initial adhesion, water resistance, dynamic stability, and removal simplicity. We review recent nanoscale strategies addressing these issues, providing a comprehensive guideline to enhance the application performance of epidermal dry electrodes. Additionally, we explore key nanoscale strategies and their associated functions, future technology roadmaps, and prospects for dry adhesive epidermal electrodes.

Bacterial adhesion and surface roughness of particulate-filled and short fiber-reinforced composites.

The objective of the study was to assess the initial adhesion of Streptococcus mutans (S. mutans) and surface roughness of different particulate-filled (PFC) and short fiber-reinforced (SFRC) composites. Five PFC composites (CeramX Universal, Filtek Universal, Omnichroma, Tetric Prime and Venus Diamond) and four SFRC composites (everX Posterior, everX Flow Bulk, everX Flow Dentin and experimental packable SFRC) were tested in this study. A non-contact 3D profilometer was employed to assess the surface roughness (Ra) of the polished specimens (using 4000-grit abrasive paper). For the bacterial adhesion test, the specimens (n = 5/group) were immersed in a solution of S. mutans to facilitate initial adhesion. To determine the number of cells on the surfaces of the discs as colony-forming units (CFU), the vials holding the microbial samples were highly agitated using a vortex machine. Subsequently, the samples were diluted multiple times and anaerobically incubated for 48h at 37°C on Mitis Salivarius Agar plates (Difco) supplemented with bacitracin. Bacterial adherence assessment was performed using SEM. The data were analyzed using ANOVA. All tested PFC and SFRC composites showed similar adhesion of S. mutan. The lowest Ra values (0.26µm) (p < 0.05) were found in the flowable SFRCs (everX Flow Bulk & Dentin), while the highest values (p < 0.05) were observed in CeramX and everX Posterior (0.42µm). Experimental SFRC had comparable Ra value (0.38µm) than other commercial composites. The presence of short microfibers in the composite appeared to have no adverse effects on the initial adhesion of bacteria or the surface roughness.

Biofilm-specific determinants of enterococci pathogen.

Amongst all Enterococcus spp., E. faecalis and E. faecium are most known notorious pathogen and their biofilm formation has been associated with endocarditis, oral, urinary tract, and wound infections. Biofilm formation involves a pattern of initial adhesion, microcolony formation, and mature biofilms. The initial adhesion and microcolony formation involve numerous surface adhesins e.g. pili Ebp and polysaccharide Epa. The mature biofilms are maintained by eDNA, It's worth noting that phage-mediated dispersal plays a prominent role. Further, the involvement of peptide pheromones in regulating biofilm maintenance sets it apart from other pathogens and facilitating the horizontal transfer of resistance genes. The role of fsr based regulation by regulating gelE expression is also discussed. Thus, we provide a concise overview of the significant determinants at each stage of Enterococcus spp. biofilm formation. These elements could serve as promising targets for antibiofilm strategies.

INNOVATIVE INSULATING MATERIAL IN THE ASPECT OF ENSURING THE SAFETY OF HYDROCARBON TRANSPORTATION

Ensuring continuous and safe operation of the main oil and gas pipelines is a critical aspect for preserving the environment and efficient use of hydrocarbon resources. More than half of accidents on trunk gas pipelines occur due to corrosion wear of the metal caused by insufficient protection of the insulation coating. The consequences of such incidents have a devastating impact on the environment and human lives: spilled oil and oil products pollute the soil, and leaking gas can lead to explosions and forest fires.Corrosion processes hiding under the coating due to poor adhesion and due to non-fulfillment of their functions by the coating lead to increased peeling of insulation and the formation of new corrosion foci, including stress-corrosion processes. Consequently, imperfect insulation coating and insufficient adhesion to metal are one of the main causes of accidents on main pipelines.The purpose of this work was to study and prove the chemical interaction of the functional groups of asmol insulation compositions with the metal surface. In the course of work, the following tasks were solved:- assessment of the ratio of initial adhesion parameters obtained in laboratory and route conditions and their values after 1.5 and 6 years of operation;- study of the IR spectrum in order to prove the presence of functional groups in the asmol material;- study of the protective capacity of the asmol coating structure in an aggressive corrosive environment at different temperatures.Methods were used to measure the quantitative adhesion of the anti-corrosion coating and the peel area during cathode polarization, in accordance with State Standard R 51164-98. The composition of the asmol material was studied by IR spectroscopy.It has been shown that functional groups, the presence of which has been confirmed by spectral analysis, of asmol material in the insulation coating make it possible to chemically adhere to steel. Indirect proof of this is the stability of the adhesion strength over time, the cohesive separation of the asmol coating in determining adhesion indicators under trace conditions and the relatively small area of coating detachment during cathode polarization.

Quantitative study of early-stage transient bacterial adhesion to bioactive glass and glass ceramics: atomic force microscopic observations

Antimicrobial potential of bioactive glass (BAG) makes it promising for implant applications, specifically overcoming the toxicity concerns associated with traditional antibacterial nanoparticles. The 58S composition of BAG (with high Ca and absence of Na) has been known to exhibit excellent bioactivity and antibacterial behaviour, but the mechanisms behind have not been investigated in detail. In this pioneering study, we are using Atomic Force Microscopy (AFM) to gain insights into 58S BAG’s adhesive interactions with planktonic cells of both gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria; along with the impact of crystallinity on antibacterial properties. We have recorded greater bacterial inhibition by amorphous BAG compared to semi-crystalline glass–ceramics and stronger effect against gram-negative bacteria via conventional long-term antibacterial tests. AFM force distance curves has illustrated substantial bonding between bacteria and BAG within the initial one second (observed at a gap of 250 ms) of contact, with multiple binding events. Further, stronger adhesion of BAG with E.coli (~ 6 nN) compared to S. aureus (~ 3 nN) has been found which can be attributed to more adhesive nano-domains (size effect) distributed uniformly on E.coli surface. This study has revealed direct evidence of impact of contact time and 58S BAG’s crystalline phase on bacterial adhesion and antimicrobial behaviour. Current study has successfully demonstrated the mode and mechanisms of initial bacterial adhesion with 58S BAG. The outcome can pave the way towards improving the designing of implant surfaces for a range of biomedical applications.

Phase-Change Stamp with Highly Switchable Adhesion and Stiffness for Damage-Free Multiscale Transfer Printing.

Transfer printing is a technology widely used in the production of flexible electronics and vertically stacked devices, which involves the transfer of predefined electronic components from a rigid donor substrate to a receiver substrate with a stamp, potentially avoiding the limitations associated with lithographic processes. However, the stamps typically used in transfer printing have several limitations related to unwanted organic solvents, substantial loading, film damage, and inadequate adhesion switching ratios. This study introduces a thermally responsive phase-change stamp for efficient and damage-free transfer printing inspired by the adhesion properties observed during water freezing and ice melting. The stamp employs phase-change composites and simple fabrication protocols, providing robust initial adhesion strength and switchability. The underlying mechanism of switchable adhesion is investigated through experimental and numerical studies. Notably, the stamp eliminates the need for extra preload by spontaneously interlocking with the ink through in situ melting and crystallization. This minimizes ink damage and wrinkle formation during pickup while maintaining strong initial adhesion. During printing, the stamp exhibits a sufficiently weak adhesion state for reliable and consistent release, enabling multiscale, conformal, and damage-free transfer printing, ranging from nano- to wafer-scale. The fabrication of nanoscale short-channel transistors, epidermal electrodes, and human-machine interfaces highlights the potential of this technique in various emerging applications of nanoelectronics, nano optoelectronics, and soft bioelectronics.

Micro/Nano Hierarchical Crater-Like Structure Surface With Mechanical Durability and Low-Adhesion for Anti-Icing/Deicing.

Superhydrophobic surfaces have attracted significant attention for their ability to prevent ice formation and facilitate deicing without requiring external energy. However, these surfaces are often vulnerable to damage from external forces, leading to functional failure due to poor mechanical stability, which limits their widespread use. Drawing inspiration from the hierarchical groove of rose petals and the micropapillae of lotus leaves, a simple laser-based method is proposed to create a superhydrophobic surface with a micro/nano hierarchical crater-like structure (HCLS). To enhance the surface, boiling water treatment is applied to induce dense nanostructures, resulting in an optimal contact angle (CA) of 162° and a desirable sliding angle (SA) of 2.0°. The initial ice adhesion strength of HCLS is as low as 1.4kPa and remains below 10kPa even after 300cm sandpaper abrasion. Furthermore, the HCLS demonstrates excellent mechanical durability, maintaining its performance under conditions that simulate the continuous impact of water and sand in extreme weather. This approach offers an innovative design concept that has the potential to advance the development of anti-icing and deicing surfaces for future aircraft.

Effect of Silicon Nitride Coating on Titanium Surface: Biocompatibility and Antibacterial Properties.

In recent years, with the advent of a super-aged society, lifelong dental care has gained increasing emphasis, and implant therapy for patients with an edentulous jaw has become a significant option. However, for implant therapy to be suitable for elderly patients with reduced regenerative and immunological capabilities, higher osteoconductive and antimicrobial properties are required on the implant surfaces. Silicon nitride, a non-oxide ceramic known for its excellent mechanical properties and biocompatibility, has demonstrated high potential for inducing hard tissue differentiation and exhibiting antibacterial properties. In this study, silicon nitride was deposited on pure titanium metal surfaces and evaluated for its biocompatibility and antibacterial properties. The findings indicate that silicon nitride improves the hydrophilicity of the material surface, enhancing the initial adhesion of rat bone marrow cells and promoting hard tissue differentiation. Additionally, the antibacterial properties were assessed using Staphylococcus aureus, revealing that the silicon nitride-coated surfaces exhibited significant antibacterial activity. Importantly, no cytotoxicity was observed, suggesting that silicon nitride-coated titanium could serve as a novel implant material.

Facile synthesis of soy protein adhesives with high cold-pressing bonding ability through waterborne epoxy resin and bifunctional branched structure system

Biomass high-temperature soy meal (HSM)-based adhesives are gaining significant attention in the green household industry. However, the low initial adhesion and poor bonding performances have limited their applications in actual production. In this study, a stable waterborne epoxy emulsion (WEU) crosslinker and polyethylenimine (PEI) toughener were synergistically used to modify the HSM matrix owing to their regulated covalent interactions and branched chemistry. The WEU was prepared using a synthetic emulsifier that featured flexible polyether and alternating amine group blocks, providing numerous hydrogen bond sites and a toughened entangled network. PEI, with a unique spatial structure, was introduced to facilitate the noncovalent interactions, and also acted as a curing agent under thermo-curing. The synthesized adhesives exhibited excellent cold-pressing bonding strength at 0.99 MPa, which is sufficient to meet actual needs. Under certain pressure and thermal conditions, covalent bonds facilitated the formation of the crosslinking network. The resulting cured adhesive exhibited improved toughness, which was attributed to the branched and multiple noncovalent energy dissipation network. The HSM15-P7 adhesive exhibited outstanding wet shear strength, which increased by 3675 % compared with that of the unmodified HSM adhesives. This HSM15-P7 adhesive exhibited outstanding results compared with other reported biomass wood adhesives. This study provides a facile and comprehensible method for developing other bioresources for high-value industry products with high performances.

Atmospheric Pressure Plasma Functionalization of Sealed PDMS Microfluidics: Application to Capillary Pumping and Enhanced Cell Growth.

Microfluidic devices serve as essential tools across diverse fields like medicine, biotechnology, and chemistry, enabling advancements in analytical techniques, point-of-care diagnostics, microfluidic cell cultures, and organ-on-chip models. While polymeric microfluidics are favoured for their cost-effectiveness and ease of fabrication, their inherent hydrophobic properties necessitate surface functionalization, often post-sealing. Here, we introduce a versatile apparatus for functionalizing sealed microfluidic devices using atmospheric plasma processing, with a focus on PDMS (polydimethylsiloxane) microfluidics. Through meticulous analysis of surface properties and capillary speed, before and after plasma treatment, along with a comparison between vacuum and atmospheric plasma functionalization methods, we demonstrate the efficacy of our approach. Subsequent experimentation within 3D PDMS microfluidic chambers, combining atmospheric pressure plasma treatment with collagen coating to facilitate mesenchymal stem cells (MSCs) growth over five days, reveals enhanced initial cell adhesion and proliferation, highlighting the potential of our method for improving cell-based applications within microfluidic systems.

Does dental material type influence bacterial adhesion under the same polishing conditions? Direct observation using a fluorescent staining technique: An in vitro study.

Highly polished 3, 4, and 5 mol% yttria-stabilized zirconia and CAD/CAM composite resin samples were prepared, and the influence of surface roughness (Ra and Sa, 21 areas/group), wettability (contact angle and surface energy, 3 samples/group), and surface chemical composition (2 samples/group) on single-strain bacterial adhesion models (Porphyromonas gingivalis, Streptococcus oralis, Streptococcus sanguinis, Streptococcus gordonii, and Streptococcus mutans) were compared via fluorescent staining with graphical analysis (21 areas/group). Statistical analysis was performed using the Shapiro-Wilk test followed by one-way analysis of variance with Tukey's test or the Kruskal-Wallis test with Dunn's test (α=0.05) and linear regression. For dental zirconia with the same surface roughness, the yttria content did not significantly influence the initial bacterial adhesion. However, higher bacterial adhesion was detected for the composite resin owing to its high C, O, and Si contents. There was no correlation between surface energy and bacterial adhesion for any bacterial strain (p<0.005).

Leaching-Free durable antibacterial composite films constructed via delicate balance between potent contact sterilization and low adhesion

Durable antibacterial surfaces are often required high bactericidal ability and low bacterial adhesion property, but the potent bactericidal surfaces, especially based on the contact bactericidal mechanism, are often paradoxically intended to attract bacteria to adhere. In this work, a delicate balance between the potent contact bactericidal action and low bacterial adhesion was successfully achieved in quaternized fluoropolymer/SiO2 composite films (QFP/SiO2 CFs) through judicious selection of a common fluorinated monomer, a common quaternary ammonium monomer, and a common inert inorganic nanoparticle, to acquire suitable surface energy and chain mobility to ensure low bacterial adhesion, as well as to allow appropriate surface-exposed quaternary ammonium units to synergistically enhance the contact bactericidal action with the specific fluorinated side chains. The QFP/SiO2 CFs were conveniently fabricated through miniemulsion polymerization and followed squeegeeing technique. The QFP/SiO2 CF with an optimized composition exhibited extremely low initial adhesion of bacteria, potent contact bactericidal action, superior long-term antibacterial performance, easy sonication-assistant regeneration for multiple usage, and low cytotoxicity with non-leachable attribute. This work may guide the design and efficient fabrication of leaching-free durable antibacterial surfaces for biological applications, as well as provide an effective strategy to balance contact bactericidal action and low bacteria adhesion for durable antibacterial performance.

Enhance PD/A biofilm formation via a novel biochar/tourmaline modified-biocarriers to treat low-strength contaminated surface water: Initial adhesion and high-substrate microenvironment

In this work, a novel polyurethane carrier modified with biochar and tourmaline/zeolite powder at ratio of 1:1 and 1:2 was developed to promote the formation of biofilms and the synergy of overall bacterial activity for Partial Denitrification/Anammox to treat low-nitrogen contaminated surface water. Based on the batch experiment, the modified biocarrier, BTP2 (biochar: tourmaline = 2: 1), exhibited the highest total nitrogen removal efficiency (83.63%) under influent total nitrogen of 15 mg/L and COD/NO3− of 3. The dense biofilm was formed in inner side of biocarrier owing to the increased surface roughness and various functional groups suggested by scanning electron microscopy and Fourier-transform infrared analysis. The EPS content increased from 200.15 to 220.26 mg/g VSS in BTP2 system. Besides, the rapid NH4+ capture and organics release of the modified carrier fueled the growth of anammox and denitrification bacteria, with the activity of 2.13 ± 0.52 mg N/gVSS/h and 6.70 ± 0.52 mg N/gVSS/h (BTP2). High-throughput sequencing unraveled the increased abundances of Candidatus_Competibacter (0.82%), Thauera (0.60%) and Candidatus_Brocadia (0.55%) which was responsible for the synergy of incomplete reduction of NO3− to NO2− and NH4+ oxidation. Overall, this study provided a valid and simple-control guide for biofilm formation towards rapid enrichment and great collaboration of Anammox and denitrification bacteria.

Optimizing small-diameter vascular grafts: Harnessing the power of recombinant human type III collagen (rhCOLIII) for enhanced antiplatelet and endothelialization performance

Small-diameter vascular grafts hold great promise as potential substitutes for coronary and peripheral arteries. However, their clinical availability is hindered by thrombogenicity and intimal hyperplasia. Herein, bilayer vascular grafts with enhanced antithrombogenicity and endothelialization were developed by two-step electrospinning technology. First, the well-designed recombinant human type III collagen (rhCOLIII), featuring numerous triplets that promote cell adhesion while excluding sequences prone to platelet adhesion and activation, was composited with poly(L-lactide-co-ε-caprolactone) (PLCL) to create a bioactive inner layer. Afterward, a pure PLCL outer layer with exceptional elasticity was constructed to provide mechanical support. In vitro antiplatelet and cytocompatibility experiments revealed that the graft containing 60% rhCOLIII exhibited almost no platelet adhesion, while the number of adhered endothelial cells increased approximately 20 times compared to pure PLCL. Furthermore, Beagle dog femoral artery implantation models demonstrated that the rhCOLIII-modified grafts underwent endothelialization within three months, contributing to the patency of grafts. The potential mechanism for enhanced endothelialization by rhCOLIII was investigated through transcriptome sequencing and verified by an integrated analysis of gene and protein expression. The cell-affinity units, Gly-Glu-Arg (GER) and Gly-Glu-Lys (GEK) triplets, present in rhCOLIII contribute to initial adhesion of endothelial cells. Following adhesion, they may upregulate the expression of integrins αVβ8 on the cell surface, thereby further enhancing cell adhesion. Subsequently, the FAK/PI3K/AKT pathway within endothelial cells may also be activated to promote cell proliferation.

A comparative study on the mechanical and antibacterial properties of BPA-free dental resin composites

ObjectiveThe commonly used base monomer utilized in resinous commercial dental restorative products is bis-GMA which is derived from bisphenol-A (BPA) - a well-known compound which may disrupt endocrine functions. To address concerns about its leaching into the oral environment and to optimize the quality of dental composites, a BPA-free alternative base monomer, fluorinated urethane dimethacrylate (FUDMA), was designed by modifying a UDMA monomer system. MethodsNine groups of composites were prepared by mixing the base monomers and TEGDMA in a ratio of 70/30 wt% to which were added silanized glass particles (mean diameter: 0.7 µm) in 3 different volume fractions (40, 45, and 50 vol%). Bis-GMA and UDMA base monomers were used as control groups in the same ratios. Various properties including degree of conversion (DC), flexural strength (FS) and flexural modulus (FM), water sorption (WS), solubility (SL), surface hardness and roughness, and initial adhesion property against S.mutans were investigated. One-way analysis of variance followed by Bonferroni test at α = 0.05 was used to analyze the results. ResultsA significant difference in FS between FUDMA-based composite with 40 vol% filler (120.3 ± 10.4 MPa) and Bis-GMA-based composite with the same filler fraction (105.8 ± 10.0 MPa) was observed but there was no significant difference among other groups. The UDMA based group exhibited the highest WS (1.3 ± 0.3 %). Bis-GMA showed greater initial bacterial adhesion but was not statistically different from the other groups (p = 0.082). SignificanceFUDMA-based resin composites exhibit comparable mechanical and bacterial adhesion properties compared with Bis-GMA and UDMA-based composites. The FUDMA composites show positive outcomes indicating they could be used as substitute composites to Bis-GMA-based composites.

Enzyme‐Assisted Activation Technique for Producing Versatile Hydrogel Microparticle Scaffolds with High Surface Chemical Reactivity

AbstractAdvancing the integration of nonliving and living components relies heavily on functional hydrogel materials with biocompatibility and customizability. In this study, an enzyme‐assisted surface activation method is developed to produce reactive hydrogel microparticles (HMPs) comprising thiolated hyaluronic acid and hyperbranched poly(β‐hydrazide esters). Fluorescence labeling analysis reveals an over six‐fold increase in surface‐active functional group density on the hydrogels and three‐fold on HMPs after enzyme activation. This enhancement improves accessibility of active elements, facilitating post‐functionalization and optimizing their capacity to support initial cell adhesion and spreading as carriers for cell cultures. Additionally, by utilizing the exposed reactive double bonds on the HMP surfaces post‐enzymatic treatment, thiolated HMPs are produced through a thiol‐ene coupling reaction with thiolated polymers. These thiolated HMPs bond together spontaneously, resulting in the formation of annealed granular hydrogels with interconnected large‐pore networks and a tunable storage modulus (G’) from tens to hundreds of pascals, compatible with most soft tissues. Integrated with 3D bioprinting, this hydrogel ink generates prints that foster cell adhesion, migration, growth, and network formation. Moving forward, integrating various granular hydrogel scaffold systems with the enzyme‐assisted activation technique holds significant promise for enhancing performance and expanding applications in regenerative medicine and innovative living materials.

Diclofenac sodium effectively inhibits the biofilm formation of Staphylococcus epidermidis.

Staphylococcus epidermidis is an opportunistic pathogen commonly implicated in medical device-related infections. Its propensity to form biofilms not only leads to chronic infections but also exacerbates the issue of antibiotic resistance, necessitating high-dose antimicrobial treatments. In this study, we explored the use of diclofenac sodium, a non-steroidal anti-inflammatory drug, as an anti-biofilm agent against S. epidermidis. In this study, crystal violet staining and confocal laser scanning microscope analysis showed that diclofenac sodium, at subinhibitory concentration (0.4 mM), significantly inhibited biofilm formation in both methicillin-susceptible and methicillin-resistant S. epidermidis isolates. MTT assays demonstrated that 0.4 mM diclofenac sodium reduced the metabolic activity of biofilms by 25.21-49.01% compared to untreated controls. Additionally, the treatment of diclofenac sodium resulted in a significant decrease (56.01-65.67%) in initial bacterial adhesion, a crucial early phase of biofilm development. Notably, diclofenac sodium decreased the production of polysaccharide intercellular adhesin (PIA), a key component of the S. epidermidis biofilm matrix, in a dose-dependent manner. Real-time quantitative PCR analysis revealed that diclofenac sodium treatment downregulated biofilm-associated genes icaA, fnbA, and sigB and upregulated negative regulatory genes icaR and luxS, providing potential mechanistic insights. These findings indicate that diclofenac sodium inhibits S. epidermidis biofilm formation by affecting initial bacterial adhesion and the PIA synthesis. This underscores the potential of diclofenac sodium as a supplementary antimicrobial agent in combating staphylococcal biofilm-associated infections.