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Although the physiochemical merits of g-C3N4-based photocatalysts have garnered increasing interest in the fields of energy and environmental science, insufficient layer detachment has created a gap between fundamental research and practical applications. To unlock the intrinsic potential of g-C3N4, a bio-transformation of the ZnMn2O4 ((6)ZM) gel was employed to introduce highly-ordered modulation caused by steric hindrance during melamine pyrolysis. Phytomediated (6)ZM reorganized traditional carbon nitride into crossed C3N4 (CCN) monolayers, simultaneously engineering an auspicious Z-schematic system ((6)ZM/CCN). Phytoconverted (6)ZM retained the crystalline-amorphous configuration for facile charge transfer and provided a large surface area (288 m2 g−1) that was 2.3 times greater than that of thermally prepared g-C3N4 (TCN) monolayers. Additionally, (6)ZM exhibited a quantum confinement-promoted reduction capability and induced bulging on CCN monolayers to fully utilize photons through multilevel light scattering and reflection. Specific sequential two-step calcination of (6)ZM/CCN, furnishing affordable dual Z-schematic VO–(6)ZM/CCN, was specifically developed to introduce a third component into the structure without incurring additional operational cost or complexity. V2O5 (VO) nanoparticles were thermally anchored on (6)ZM/CCN to achieve highly efficient levofloxacin (LFC) detoxification under visible-light irradiation. After optimizing all effective synthesis parameters and experimental variables, VO–(6)ZM/CCN exhibited unsurpassed activity, achieving complete LFC photodegradation (50 mg L−1) within 120 min, which was 10.7, 8.7, and 24.7 times more kinetically efficient than the photodegradations achieved by (6)ZM, TCN, and VO, respectively. The outstanding performance of VO–(6)ZM/CCN was evident through complete mineralization of LFC, excellent decontamination of pharmaceutical wastewater within 300 min, resistance to performance deterioration during successive cycling runs, and the corresponding postcharacterization. The combination of simultaneous Z-scheme formation with photogenic (6)ZM provides a promising strategy to bridge the gap between experimental investigations and industrial applications of g-C3N4. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Hyaluronic Acid/Collagen Nanofiber Tubular Scaffolds Support Endothelial Cell Proliferation, Phenotypic Shape and Endothelialization" published in the journal Nanomaterials. The correction addresses errors in Figures 1B, 2A, and 5A of the original publication. The corrected figures are provided in the document. The authors apologize for any inconvenience caused but state that the scientific conclusions of the article remain unaffected. [Extracted from the article]

Artificial intelligent actuators are extensively explored for emerging applications such as soft robots, human‐machine interfaces, and biomedical devices. However, intelligent actuating systems based on synthesized polymers suffer from challenges in renewability, sustainability, and safety, while natural polymer‐based actuators show limited capabilities and performances due to the presence of abundant hydrogen‐bond lockers. Here this study reports a new hydrogen bond‐mediated strategy to develop mimosa‐inspired starch actuators (SA). By harnessing the unique features of gelatinization and abundant hydrogen bonds, these SA enable high‐sensitivity and multi‐responsive actuation in various scenarios. The non‐gelatinized SA can be irreversibly programmed into diverse shapes, such as artificial flowers, bowl shapes, and helix structures, using near‐infrared light. Furthermore, the gelatinized SA exhibit reversibly multi‐responsive actuation when exposed to low humidity (10.2%), low temperature (37 °C), or low‐energy light (0.42 W cm−2). More importantly, the SA demonstrate robust applications in smart living, including artificial mimosa, intelligent lampshade, and morphing food. By overcoming the hydrogen‐bond lockers inherent in natural polymers, SA open new avenues for next‐generation recyclable materials and actuators, bringing them closer to practical applications. [ABSTRACT FROM AUTHOR]

Single- or few-layer forms of black phosphorus, so called phosphorene, were isolated by exfoliation in 2014 as 2D layered materials holding great promise in electronic and optoelectronic fields. In this perspective, we highlight recent developments in black phosphorus research, in particular, we will focus on the mechanical properties of its 2D form. Its unique puckered structure is responsible for strong anisotropy in mechanical and transport properties, different from graphene and transition-metal dichalcogenide 2D materials. This peculiar mechanical anisotropy can be exploited for applications such as nanomechanical resonators, thermoelectric devices, and motion sensors with tunable functions inaccessible by isotropic materials. Current bottlenecks hindering further progress in devices applications involve first surface degradation in environmental conditions which, in turn, can be exploited in surface friction mechanics to achieve superlubricity. In this framework, the investigation of mechanical properties of phosphorene will be pivotal for facile fabrication, transfer, and resolution of technical hurdles as well the discovery of novel applications. As research directions in next foreseeable future, we will discuss the challenge of crosstalk between mechanical and transport properties, in particular, how the stress–strain stimulations can be used to tune optoelectronic and thermoelectric performance. [ABSTRACT FROM AUTHOR]

Air pollution is known as one of the most important causes of death in the whole world. Therefore, pollution reduction to achieve clean air was noticed by everyone. This way, using nanotechnology to control air and monitor is a novel approach. This paper investigates the effect of the number of graphene nano-pores on the SiO 2 separation from the H 2 O vapour in the presence of an external electric field with the magnitude of 0.01 V/Å using the molecular dynamics (MD) method. The electric field affects the charged particles and causes disturbance in the structure. It also prevents SiO 2 nanoparticles from passing through the graphene nanosheet. Also, the presence of carbon nanosheets acts as a membrane and affects the diffusion of water in the nanostructure. So, the results show that in the presence of a nano-pore, the number of H 2 O molecules reaches to 496 and 568 in reservoirs 2 and 3. Also, the number of SiO 2 nanoparticles reaches 10 and 4 in reservoirs 2 and 3. This shows that in reservoirs 2 and 3, about 80% and 60% of the SiO 2 nanoparticles are separated. As mentioned before, the electric field prevents the passage of SiO 2 nanoparticles through the graphene nanosheet. As the number of graphene nano-pores increases by 2, 3, 4, and 5, the number of passing water molecules increases. Considering that the number of graphene nano-pores has increased and the movement path of particles has increased, the number of passing particles almost increases. However, the electric field prevents the passage of SiO 2 nanoparticles. According to the results, the suggested setup can be employed for designing highly efficient nanostructured membranes for air purification and monitoring. [Display omitted] [ABSTRACT FROM AUTHOR]

The cytotoxicity of ionic liquids (ILs) has been receiving attention in the context of the biological and environmental impact of their vast field of applications. It has been ascertained that the cell membrane is the main target of ILs when they interact with microorganisms, cells and bacteria; nevertheless, studies at the micro- and nano-scale aiming at better understanding of the fundamental mechanisms of toxicity of ILs are lacking. In this work, we used atomic force microscopy (AFM) to investigate the impact of room-temperature ILs on the mechanical, morphological and electrostatic properties of solid-supported DOPC phospholipid bilayers, taken as models of biomembranes. In particular, we have characterized the concentration-dependent and time-dependent evolution of the morphological, structural and mechanical properties of DOPC lipid membranes in the presence of imidazolium-based ILs with different alkyl chain lengths and hydrophilic/hydrophobic characteristics. The majority of ILs investigated were found to possess the ability of restructuring the lipid bilayer, through the formation of new IL/lipid complexes, showing distinctive morphological features (increase of area and roughness). The nanomechanical analysis of the lipid membrane exposed to ILs revealed a progressive, concentration-dependent perturbation of the structural ordering and rigidity of the membrane, evidenced by a decrease in the breakthrough force, Young's modulus and area stretching modulus. AFM detected a modification of the electrostatic double-layer at the membrane surface, in terms of a reduction of the original negative surface charge density, suggesting a progressive stratification of cations on the exposed leaflet of the lipid membrane. Our findings may be helpful in designing novel ILs with tailored interaction with biological membranes. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the regulatory effect of hyaluronic acid (HA)—coating silk fibroin (SF) nanofibers during epithelialization of urinary tract for urethral regeneration. The obtained electrospun biomimetic tubular HA‐SF nanofiber scaffold is composed of a dense inner layer and a porous outer layer in order to mimic adhesion and cavernous layers of the native tissue, respectively. A thin layer of HA‐gel coating was fixed in the inner wall to provide SF nanofibers with a dense and smooth surface nano‐topography and higher hydrophilicity. Compared with pure SF nanofibers, HA‐SF nanofibers significantly promoted the adhesion, growth, and proliferation of primary urothelial cells, and up‐regulate the expression of uroplakin‐3 (terminal differentiation keratin protein in urothelium). Using the New Zealand male rabbit urethral injury model, the scaffold composed of tubular HA‐SF nanofibers could recruit lumen and myoepithelial cells from the adjacent area of the host, rapidly reconstructing the urothelial barrier in the wound area in order to keep the urinary tract unobstructed, thereby promoting luminal epithelialization, smooth muscle bundle structural remodeling, and capillary formation. Overall, the synergistic effects of nano‐topography and biophysical cues in a biomimetic scaffold design for effective endogenous regeneration. [ABSTRACT FROM AUTHOR]

Chemodynamic therapy (CDT) is an emerging treatment that usually employs chemical agents to decompose hydrogen peroxide (H2O2) into hydroxyl radical (•OH) via Fenton or Fenton‐like reactions, inducing cell apoptosis or necrosis by damaging biomacromolecules such as, lipids, proteins, and DNA. Generally, CDT shows high tumor‐specificity and minimal‐invasiveness in patients, thus it has attracted extensive research interests. However, the catalytic reaction efficiency of CDT is largely limited by the relatively high pH at the tumor sites. Herein, a 808 nm laser‐potentiated peroxidase catalytic/mild‐photothermal therapy of molybdenum diphosphide nanorods (MoP2 NRs) is developed to improve CDT performance, and simultaneously achieve effective tumor eradication and anti‐infection. In this system, MoP2 NRs exhibit a favorable cytocompatibility due to their inherent excellent elemental biocompatibility. Upon irradiation with an 808 nm laser, MoP2 NRs act as photosensitizers to efficiently capture the photo‐excited band electrons and valance band holes, exhibiting enhanced peroxidase‐like catalytic activity to sustainedly decompose tumor endogenous H2O2 to •OH, which subsequently destroy the cellular biomacromolecules both in tumor cells and bacteria. As demonstrated both in vitro and in vivo, this system exhibits a superior therapeutic efficiency with inappreciable toxicity. Hence, the work may provide a promising therapeutic technique for further clinical applications. [ABSTRACT FROM AUTHOR]

Reconstruction of peripheral nerve defects with tissue engineered nerve scaffolds is an exciting field of biomedical research and holds potential for clinical application. However, due to poor neovascularization after the implantation, nerve regeneration is still not satisfactory, especially for large nerve defects. These obstacles hinder the investigation of basic neurobiological principles and development of a wide range of treatments for peripheral nerve diseases. Herein, we designed an amphiphilic alternating block polyurethane (abbreviated as PU) copolymer-based nerve guidance scaffold, which has good Schwann cell compatibility, and more importantly, a rapid vascularization of the scaffold in vivo. In the sciatic nerve transection model of SD rats, vascularized PU nerve guidance scaffolds induced rapid regeneration of nerve fibers and axons along the scaffold. Through the analysis of nerve electrophysiology, sciatic nerve functional index, histology, and immunofluorescence related to angiogenesis, we determined that PU with rapid vascularization function enhances recovery and re-obtains nerve conduction function. Our study points out a new strategy of using nerve tissue engineering scaffolds to treat large nerve defects. [ABSTRACT FROM AUTHOR]

The combination of thermoresponsive polymers with natural biomaterials can extend the properties portfolio, especially in the field of biomedicine, where a great cell adhesiveness and biodegradation is necessary for bone regeneration. The poly(N‐isopropylacrylamide)‐grafted‐gelatin gels were already reported where several synthetic parameters, such as polymer or gelatin were varied and final properties were studied. Nevertheless, the ratio of the cross‐linker was always the same, and consequently, their properties were not analyzed yet. There are various preparation methods of these systems but microwave synthesis was not deeply studied, and consequently, important benefits can be obtained due to its efficiency and time saving. In this work, we modified the ratio of cross‐linker and important changes are observed in the thermoresponsive and mechanical properties tested by calorimetry, thermogravimetry, rheology, and atomic force microscopy. The amount of cross‐linker modulates the homogeneity of the resulting gels, and consequently, the lower critical solution temperature, the absorption of water into surfaces and the mechanical behavior of the new materials. [ABSTRACT FROM AUTHOR]

Random copolymer gels of N-isopropylacrylamide (NIPAM) and N-ethylacrylamide (NEAM) are synthesized using different monomer compositions in 1:1 methanol-water mixtures. The samples are characterized by scanning electron microscopy, atomic force microscopy (AFM), and rheological studies. It is observed that with the variation of the monomer compositions in the reaction mixture, the thermoresponsive, morphological, AFM, and rheological properties varied significantly. Porosity and roughness of the gels gradually increase with the gradual increase in NIPAM loading in the gels, lower critical solution temperature, mechanical strength (Young's modulus, storage modulus) significantly decreases with the increase in poly( N-isopropylacrylamide) loading in the gels. All results can be explained on the basis of the differences in thermoresponsive character of homo- and copolymer gels of NIPAM and NEAM in water, their composition in the reaction mixtures, and their different kind of interactions with solvents. [ABSTRACT FROM AUTHOR]

Background: Thanks to mechanotransductive components cells are competent to perceive nanoscale topographical features of their environment and to convert the immanent information into corresponding physiological responses. Due to its complex configuration, unraveling the role of the extracellular matrix is particularly challenging. Cell substrates with simplified topographical cues, fabricated by top-down micro- and nanofabrication approaches, have been useful in order to identify basic principles. However, the underlying molecular mechanisms of this conversion remain only partially understood. Results: Here we present the results of a broad, systematic and quantitative approach aimed at understanding how the surface nanoscale information is converted into cell response providing a profound causal link between mechanotransductive events, proceeding from the cell/nanostructure interface to the nucleus. We produced nanostructured ZrO2 substrates with disordered yet controlled topographic features by the bottom-up technique supersonic cluster beam deposition, i.e. the assembling of zirconia nanoparticles from the gas phase on a flat substrate through a supersonic expansion. We used PC12 cells, a well-established model in the context of neuronal differentiation. We found that the cell/nanotopography interaction enforces a nanoscopic architecture of the adhesion regions that affects the focal adhesion dynamics and the cytoskeletal organization, which thereby modulates the general biomechanical properties by decreasing the rigidity of the cell. The mechanotransduction impacts furthermore on transcription factors relevant for neuronal differentiation (e.g. CREB), and eventually the protein expression profile. Detailed proteomic data validated the observed differentiation. In particular, the abundance of proteins that are involved in adhesome and/or cytoskeletal organization is striking, and their up- or downregulation is in line with their demonstrated functions in neuronal differentiation processes. Conclusion: Our work provides a deep insight into the molecular mechanotransductive mechanisms that realize the conversion of the nanoscale topographical information of SCBD-fabricated surfaces into cellular responses, in this case neuronal differentiation. The results lay a profound cell biological foundation indicating the strong potential of these surfaces in promoting neuronal differentiation events which could be exploited for the development of prospective research and/or biomedical applications. These applications could be e.g. tools to study mechanotransductive processes, improved neural interfaces and circuits, or cell culture devices supporting neurogenic processes. [ABSTRACT FROM AUTHOR]

Atomic Force Microscopy (AFM) has a great potential as a tool to characterize mechanical and morphological properties of living cells; these properties have been shown to correlate with cells' fate and patho-physiological state in view of the development of novel early-diagnostic strategies. Although several reports have described experimental and technical approaches for the characterization of cellular elasticity by means of AFM, a robust and commonly accepted methodology is still lacking. Here, we show that micrometric spherical probes (also known as colloidal probes) are well suited for performing a combined topographic and mechanical analysis of living cells, with spatial resolution suitable for a complete and accurate mapping of cell morphological and elastic properties, and superior reliability and accuracy in the mechanical measurements with respect to conventional and widely used sharp AFM tips. We address a number of issues concerning the nanomechanical analysis, including the applicability of contact mechanical models and the impact of a constrained contact geometry on the measured Young's modulus (the finite-thickness effect). We have tested our protocol by imaging living PC12 and MDA-MB-231 cells, in order to demonstrate the importance of the correction of the finite-thickness effect and the change in Young's modulus induced by the action of a cytoskeleton-targeting drug. [ABSTRACT FROM AUTHOR]

The urokinase-type plasminogen activator receptor ( uPAR) is a non-integrin vitronectin (VN) cell adhesion receptor linked to the plasma membrane by a glycolipid anchor. Through structure-function analyses of uPAR, VN and integrins, we document that uPAR-mediated cell adhesion to VN triggers a novel type of integrin signalling that is independent of integrin-matrix engagement. The signalling is fully active on VN mutants deficient in integrin binding site and is also efficiently transduced by integrins deficient in ligand binding. Although integrin ligation is dispensable, signalling is crucially dependent upon an active conformation of the integrin and its association with intracellular adaptors such as talin. This non-canonical integrin signalling is not restricted to uPAR as it poses no structural constraints to the receptor mediating cell attachment. In contrast to canonical integrin signalling, where integrins form direct mechanical links between the ECM and the cytoskeleton, the molecular mechanism enabling the crosstalk between non-integrin adhesion receptors and integrins is dependent upon membrane tension. This suggests that for this type of signalling, the membrane represents a critical component of the molecular clutch. [ABSTRACT FROM AUTHOR]

To test the biocompatiblecharacter of room-temperature ionic liquids(ILs), the interaction of various ILs with biological membrane (biomembrane)models was studied in this work. Dioleoyl phosphatidylcholine (DOPC)adsorbed on a mercury (Hg) electrode forms an impermeable defect-freemonolayer which is a well established biomembrane model, prone tobe studied by electrochemical techniques. We have monitored the modificationsof the Hg supported monolayer caused by ILs using rapid cyclic voltammetry(RCV), alternating current voltammetry (ACV), and electrochemicalimpedance spectroscopy (EIS). A series of imidazolium-based ILs wereinvestigated whose interaction highlighted the role of anion and lateralside chain of cation during the interaction with DOPC monolayers.It was shown that the hydrophobic and lipophilic character of theIL cations is a primary factor responsible for this interaction. Hg-supportedmonolayers provide an accurate analysis of the behavior of ILs atthe interface of a biomembrane leading to a comprehensive understandingof the interaction mechanisms involved. At the same time, these experimentsshow that the Hg-phospholipid model is an effective toxicity sensingtechnique as shown by the correlation between literature in vivo toxicitydata and the data from this study. [ABSTRACT FROM AUTHOR]

In this study, we designed and synthetized artificial vascular scaffolds based on nanofibers of collagen functionalized with hyaluronic acid (HA) in order to direct the phenotypic shape, proliferation, and complete endothelization of mouse primary aortic endothelial cells (PAECs). Layered tubular HA/collagen nanofibers were prepared using electrospinning and crosslinking process. The obtained scaffold is composed of a thin inner layer and a thick outer layer that structurally mimic the layer the intima and media layers of the native blood vessels, respectively. Compared with the pure tubular collagen nanofibers, the surface of HA functionalized collagen nanofibers has higher anisotropic wettability and mechanical flexibility. HA/collagen nanofibers can significantly promote the elongation, proliferation and phenotypic shape expression of PAECs. In vitro co-culture of mouse PAECs and their corresponding smooth muscle cells (SMCs) showed that the luminal endothelialization governs the biophysical integrity of the newly formed extracellular matrix (e.g., collagen and elastin fibers) and structural remodeling of SMCs. Furthermore, in vitro hemocompatibility assays indicated that HA/collagen nanofibers have no detectable degree of hemolysis and coagulation, suggesting their promise as engineered vascular implants. [ABSTRACT FROM AUTHOR]

Plasticity and functional diversity of macrophages play an important role in resisting pathogens invasion, tumor progression and tissue repair. At present, nanodrug formulations are becoming increasingly important to induce and control the functional diversity of macrophages. In this framework, the internalization process of nanodrugs is co-regulated by a complex interplay of biochemistry, cell physiology and cell mechanics. From a biophysical perspective, little is known about cellular mechanics' modulation induced by the nanodrug carrier's internalization. In this study, we used the polylactic-co-glycolic acid (PLGA)–polyethylene glycol (PEG) nanofibers as a model drug carrier, and we investigated their influence on macrophage mechanics. Interestingly, the nanofibers internalized in macrophages induced a local increase of stiffness detected by atomic force microscopy (AFM) nanomechanical investigation. Confocal laser scanning microscopy revealed a thickening of actin filaments around nanofibers during the internalization process. Following geometry and mechanical properties by AFM, indentation experiments are virtualized in a finite element model simulation. It turned out that it is necessary to include an additional actin wrapping layer around nanofiber in order to achieve similar reaction force of AFM experiments, consistent with confocal observation. The quantitative investigation of actin reconfiguration around internalized nanofibers can be exploited to develop novel strategies for drug delivery. [ABSTRACT FROM AUTHOR]

Nanohybrids of graphene with water soluble polymer were synthesized using 'grafting from' method. GO, prepared by modified Hummers' method, was first reacted with sodium azide. Alkyne-terminated RAFT-CTA was synthesized by reaction of propargyl alcohol and S-1-dodecyl-S'-(α,α'-dimethyl-α'-acetic acid) trithiocarbonate. RAFT-CTA was grafted onto the GO sheets by facile click-reaction and subsequently, N-isopropylacrylamide (NIPAM) and N-ethyleacrylamide (NEAM) were polymerized on graphene sheets via RAFT polymerization method. The respective copolymers with different ratios were also prepared. The nanohybrids were characterized by FTIR, XRD, TGA, Raman, SEM, and AFM. Both SEM and AFM clearly showed rod-like structures for rGO-PNEAM. XRD showed a small peak at 2θ = 19.21°, corresponding to d-spacing ≈ 4.6 Å. In addition, the nanohybrids showed a very broad temperature range for the LCST in water between ca. 30 and 70 °C. [ABSTRACT FROM AUTHOR]

The molecular clutch (MC) model proposes that actomyosin-driven force transmission permits integrin-dependent cell migration. To investigate the MC, we introduced diverse talin (TLN) and integrin variants into Flp-In™ T-Rex™ HEK293 cells stably expressing uPAR. Vitronectin variants served as substrate providing uPAR-mediated cell adhesion and optionally integrin binding. This particular system allowed us to selectively analyse key MC proteins and interactions, effectively from the extracellular matrix substrate to intracellular f-actin, and to therewith study mechanobiological aspects of MC engagement also uncoupled from integrin/ligand binding. With this experimental approach, we found that for the initial PIP 2 -dependent membrane/TLN/f-actin linkage and persistent lamellipodia formation the C-terminal TLN actin binding site (ABS) is dispensable. The establishment of an adequate MC-mediated lamellipodial tension instead depends predominantly on the coupling of this C-terminal TLN ABS to the actomyosin-driven retrograde actin flow force. This lamellipodial tension is crucial for full integrin activation eventually determining integrin-dependent cell migration. In the integrin/ligand-independent condition the frictional membrane resistance participates to these processes. Integrin/ligand binding can also contribute but is not necessarily required. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hyaluronic acid (HA)-functionalized PLA tubular microfibers were designed and synthetized by electrospinning. • The resulting HA/PLA microfibers have no detectable trace of hemolysis and coagulation. • The HA/PLA microfibers promoted vascular endothelial cells proliferation and phenotypic expression. • The tubular HA/PLA based tubular scaffolds enhanced luminal pre-endothelialization of vascular ECs in vitro. This work was designed to evaluate the efficacy of hyaluronic acid (HA) functionalized tubular poly-lactic acid (PLA) microfibers in directing the luminal pre-endothelialization of vascular endothelial cells (ECs). Tubular HA/PLA microfibers with hierarchical architecture were prepared by electrospinning and chemical cross-linking process. A layer of HA microfibrous film coating was fixed on the inner wall surface of the tubular HA/PLA microfibers, resulting in higher anisotropy wettability and relatively lower surface energy and roughness. We confirmed that HA coating on PLA microfibers surface have reduced hemolytic activity and coagulation degree. Mouse vascular ECs exhibited surface-dependent differences in cell elongation and proliferation (HA/PLA > PLA). Compared with PLA microfibers, the gene expression levels of platelet EC adhesion molecule-1 (PECAM-1/CD31) and vascular endothelial growth factor (VEGF) in ECs of HA/PLA microfibers surface were up-regulated. Immunostaining analysis revealed that the surface of HA/PLA nanofibers supported the expression of mature vascular EC phenotype CD31 protein. In vitro co-culture analysis showed that the luminal pre-endothelialization induced vascular smooth muscle cells (SMCs) to maintain their phenotypic shape and establish natural behavior patterns in the hierarchical tubular scaffold. These studies indicate that the biophysical cues of scaffolds are potent regulators of vascular EC endothelialization. [ABSTRACT FROM AUTHOR]

Macrophages are involved in every stage of the innate/inflammatory immune responses in the body tissues, including the resolution of the reaction, and they do so in close collaboration with the extracellular matrix (ECM). Simplified substrates with nanotopographical features attempt to mimic the structural properties of the ECM to clarify the functional features of the interaction of the ECM with macrophages. We still have a limited understanding of the macrophage behavior upon interaction with disordered nanotopography, especially with features smaller than 10 nm. Here, we combine atomic force microscopy (AFM), finite element modeling (FEM), and quantitative biochemical approaches in order to understand the mechanotransduction from the nanostructured surface into cellular responses. AFM experiments show a decrease of macrophage stiffness, measured with the Young's modulus, as a biomechanical response to a nanostructured (ns-) ZrO x surface. FEM experiments suggest that ZrO x surfaces with increasing roughness represent weaker mechanical boundary conditions. The mechanical cues from the substrate are transduced into the cell through the formation of integrin-regulated focal adhesions and cytoskeletal reorganization, which, in turn, modulate cell biomechanics by downregulating cell stiffness. Surface nanotopography and consequent biomechanical response impact the overall behavior of macrophages by increasing movement and phagocytic ability without significantly influencing their inflammatory behavior. Our study suggests a strong potential of surface nanotopography for the regulation of macrophage functions, which implies a prospective application relative to coating technology for biomedical devices.

The cytoskeleton is involved during movement, shaping, resilience, and functionality in immune system cells. Biomarkers such as elasticity and adhesion can be promising alternatives to detect the status of cells upon phenotype activation in correlation with functionality. For instance, professional immune cells such as macrophages undergo phenotype functional polarization, and their biomechanical behaviors can be used as indicators for early diagnostics. For this purpose, combining the biomechanical sensitivity of atomic force microscopy (AFM) with the automation and performance of a deep neural network (DNN) is a promising strategy to distinguish and classify different activation states. To resolve the issue of small datasets in AFM-typical experiments, nanomechanical maps were divided into pixels with additional localization data. On such an enlarged dataset, a DNN was trained by multimodal fusion, and the prediction was obtained by voting classification. Without using conventional biomarkers, our algorithm demonstrated high performance in predicting the phenotype of macrophages. Moreover, permutation feature importance was employed to interpret the results and unveil the importance of different biophysical properties and, in turn, correlated this with the local density of the cytoskeleton. While our results were demonstrated on the RAW264.7 model cell line, we expect that our methodology could be opportunely customized and applied to distinguish different cell systems and correlate feature importance with biophysical properties to unveil innovative markers for diagnostics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Zhang, Zhao, Yang and Galluzzi.)

Direct neuronal reprogramming of somatic cells into induced neurons (iNs) has been recently established as a promising approach to generating neuron cells. Previous studies have reported that the biophysical cues of the in vitro microenvironment are potent modulators in the cell fate decision; thus, the present study explores the effects of a customized pattern (named colloidal self-assembled patterns, cSAPs) on iN generation from human fibroblasts using small molecules. The result revealed that the cSAP, composed of binary particles in a hexagonal-close-packed (hcp) geometry, is capable of improving neuronal reprogramming efficiency and steering the ratio of the iN subtypes. Cells exhibited distinct cell morphology, upregulated cell adhesion markers (i.e., SDC1 and ITGAV), enriched signaling pathways (i.e., Hippo and Wnt), and chromatin remodeling on the cSAP compared to those on the control substrates. The result also showed that the iN subtype specification on cSAP was surface-dependent; therefore, the defined physicochemical cue from each cSAP is exclusive. Our findings show that direct cell reprogramming can be manipulated through specific biophysical cues on the artificial matrix, which is significant in cell transdifferentiation and lineage conversion.

The immune response of macrophages plays an important role in defending against viral infection, tumor deterioration and repairing of contused tissue. Macrophage functional differentiation induced by nanodrugs is the leading edge of current research, but nanodrugs have toxic side effects, and the influence of their physical properties on macrophages is not clear. Here we create an alternative way to modulate macrophage function through PLGA-PEG fibers' Young's modulus. Previously, we revealed that by controlling the Young's modulus of the fibers from kPa to MPa, all the fibers entered murine macrophage cells (RWA 264.7) in a similar manner, and based on that, we found that macrophages' mechanical properties were affected by the fibers' Young's modulus, that is, hard fibers with a Young's modulus of ∼1 MPa increased the cell average Young's modulus, but did not affect the cell shape, while soft fibers with a Young's modulus of ∼100 kPa decreased the cell average Young's modulus and modulated the cell shape to a more spherical one. On the other hand, only the soft fibers induced proinflammatory cytokine secretion, indicating an M1 macrophage functional modulation by low Young's modulus fibers. This study explored the mechanical properties of the interactions between PLGA-PEG fibers and cells, in particular, when guiding the direction of the modulation of macrophage function, which is of great significance for the applications of material biology in the biomedical field.

Polydopamine (PDA) is a biocompatible cell-adhesive polymer with versatile applications in biomedical devices. Previous studies have shown that PDA coating could improve cell adhesion and differentiation of human mesenchymal stem cells (hMSCs). However, there is still a knowledge gap in the effect of PDA-mediated protein adsorption on the epigenetic status of MSCs. This work used gelatin-coated cell culture surfaces with and without PDA underlayer (Gel and PDA-Gel) to culture and differentiate primary human adipose-derived stem cells (hASCs). The properties of these two substrates were significantly different, which, in combination with a variation in extracellular matrix (ECM) protein bioactivity, regulated cell adhesion and migration. hASCs reduced focal adhesions by downregulating the expression of integrins such as αV, α1, α2, and β1 on the PDA-Gel compared to the Gel substrate. Interestingly, the ratio of H3K27me3 to H3K27me3+H3K4me3 was decreased, but this only occurred for upregulation of AGG and BMP4 genes during chondrogenic differentiation. This result implies that the PDA-Gel surface positively affects the chondrogenic, but not adipogenic and osteogenic, differentiation. In conclusion, for the first time, this study demonstrates the sequential effects of PDA coating on the biophysical property of adsorbed protein and then focal adhesions and differentiation of hMSCs through epigenetic regulation. This study sheds light on PDA-mediated mechanotransduction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Harati, Tao, Shahsavarani, Du, Galluzzi, Liu, Zhang, Shaw, Shokrgozar, Pan and Wang.)

This study was designed to investigate the regulatory effect of hyaluronic acid (HA)-coating silk fibroin (SF) nanofibers during epithelialization of urinary tract for urethral regeneration. The obtained electrospun biomimetic tubular HA-SF nanofiber scaffold is composed of a dense inner layer and a porous outer layer in order to mimic adhesion and cavernous layers of the native tissue, respectively. A thin layer of HA-gel coating was fixed in the inner wall to provide SF nanofibers with a dense and smooth surface nano-topography and higher hydrophilicity. Compared with pure SF nanofibers, HA-SF nanofibers significantly promoted the adhesion, growth, and proliferation of primary urothelial cells, and up-regulate the expression of uroplakin-3 (terminal differentiation keratin protein in urothelium). Using the New Zealand male rabbit urethral injury model, the scaffold composed of tubular HA-SF nanofibers could recruit lumen and myoepithelial cells from the adjacent area of the host, rapidly reconstructing the urothelial barrier in the wound area in order to keep the urinary tract unobstructed, thereby promoting luminal epithelialization, smooth muscle bundle structural remodeling, and capillary formation. Overall, the synergistic effects of nano-topography and biophysical cues in a biomimetic scaffold design for effective endogenous regeneration., Competing Interests: All authors declared no potential conflicts of interest., (© 2021 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)