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Cobalt-based nanoparticles exhibit considerable potential as bi-functional electrocatalyst materials in diverse renewable energy systems due to their exceptional qualities, which include highly active catalytic characteristics, remarkable thermal and chemical stability, and super-dynamic behavior. However, several drawbacks remain, including poor conductivity and structural stability. The current advancements in surface nano-topography modification for cobalt-based nanomaterials serving as bifunctional electrocatalyst materials for renewable energy devices were discussed in this review. It discusses the fabrication methods of the materials, surface engineering strategies, and resulting enhancement mechanisms for good performance at the surface nano-topography. The influence of several surface nano-topology modification approaches on improved charge transfer, increased surface area and electrocatalytic activity, and reaction intermediate stabilization is also examined. In addition, engineering the surface morphology using a template-assisted doping strategy and etching process can produce enhancement mechanisms such as increased surface area, porous network, and more reactive active sites. This review is highly dedicated to the research of several cobalt-based nanomaterials in renewable energy devices and that there will be new frontiers in surface engineering strategies by upcoming scholars. • Focus on surface nano-topography modification for cobalt-based nanomaterials as bifunctional electrocatalysts. • Reveal recent developments for good catalytic performance at the surface nano-topography. • Strategies for overcoming the challenges and recent advances for ground-breaking future research are proposed. [ABSTRACT FROM AUTHOR]

Currently, biomineralization is widely used as a surface modification approach to obtain ideal material surfaces with complex hierarchical nanostructures, morphologies, unique biological functions, and categorized organizations. The fabrication of biomineralized coating for the surfaces of scaffolds, especially synthetic polymer scaffolds, can alter surface characteristics, provide a favorable microenvironment, release various bioactive substances, regulate the cellular behaviors of osteoblasts, and promote bone regeneration after implantation. However, the biomineralized coating fabricated by immersion in a simulated body fluid has the disadvantages of non-uniformity, instability, and limited capacity to act as an effective reservoir of bioactive ions for bone regeneration. In this study, in order to promote the osteoinductivity of 3D-printed PCL scaffolds, we optimized the surface biomineralization procedure by nano-topographical guidance. Compared with biomineralized coating constructed by the conventional method, the nano-topographically guided biomineralized coating possessed more mineral substances and firmly existed on the surface of scaffolds. Additionally, nano-topographically guided biomineralized coating possessed better protein adsorption and ion release capacities. To this end, the present work also demonstrated that nano-topographically guided biomineralized coating on the surface of 3D-printed PCL scaffolds can regulate the cellular behaviors of USCs, guide the osteogenic differentiation of USCs, and provide a biomimetic microenvironment for bone regeneration. [ABSTRACT FROM AUTHOR]

Objectives: Dental implants are currently becoming a routine treatment decision in dentistry. Synthetic polyetheretherketone (PEEK) polymer is a prevalent component of dental implantology field. The current study aimed to assess the influence of Nd:YAG laser nano-topographical surface engineering combined with ultraviolet light or platelet rich fibrin on the bioactivity and osseointegration of PEEK implants in laboratory and animal testing model. Materials and methods: Computer Aided Design-Computer Aided Manufacturing (CAD CAM) discs of PEEK were used to fabricate PEEK discs (8 mm × 3 mm) N = 36 and implant cylinders (3 mm × 6 mm) N = 72. Specimens were exposed to Nd:YAG laser at wavelength 1064 nm, and surface roughness topography/Ra parameter was recorded in nanometer using atomic force microscopy. Laser modified specimens were divided into three groups: Nd:YAG laser engineered surfaces (control), Nd:YAG laser/UV engineered surfaces and Nd:YAG laser/PRF engineered surfaces (N = 12 discs–N = 24 implants). In vitro bioactivity test was performed, and precipitated apatite minerals were assessed with X-ray diffraction analysis (XRD) and scanning electron microscopy (SEM). In vivo histomorphometric analysis was performed in rabbits with BIC% calculation. Results: Ra mean value of PEEK laser engineered surfaces was 125.179 nm. For the studied groups, XRD patterns revealed distinctive peaks of different apatite minerals that were demonstrated by SEM as dispersed surface aggregations. There was a significant increase in the BIC% from control group 56.43 (0.97) to laser/UV surfaces 77.30 (0.78) to laser/PRF 84.80 (1.29) (< 0.0001). Conclusions: Successful engineered nano-topographical biomimetic PEEK implant could be achieved by Nd:YAG laser technique associated with improving bioactivity. The combination with UV or PRF could be simple and economic methods to gain more significant improvement of PEEK implant surface bioactivity with superior osteointegration. [ABSTRACT FROM AUTHOR]

Interproximal enamel reduction is a part of the orthodontic treatment as a method of space generation in addition to other vast indications. Some studies found that different techniques might impose changes to the enamel surface that alter its topography, which in turn might influence its integrity and susceptibility to caries. Polishing, however, after this procedure is thought to be helpful to reduce these adverse effects. To evaluate the nano-topography of the enamel surfaces after interproximal reduction (IPR) and determine its influence on enamel surface roughness and examine the need for polishing to minimise these influences, when combined with topical fluoride application. A total of 60 proximal surfaces of 40 extracted maxillary premolars (10 premolars left unprepared as the control group) were reduced with different stripping instruments (discs, burs and manual strip system). The surface roughness of enamel was analysed with an atomic force microscope to determine the results quantitatively as well as qualitatively on the nanoscopic scale. One of each proximal surface was followed by polishing and fluoride varnish after the reduction. The results showed that surface roughness was increased in all groups without polishing. The greatest mean roughness was recorded for the disc group (212 ±125.7), followed by the bur group (172 ±93.1) and manual strips (153.8±106.7). The difference between the groups, however, was not significant for both mean roughness (P = 0.656) and height (P = 0.737). The parameters were decreased after polishing in all groups but the difference between methods was not significant for both parameters (P = 0.946 and P = 0.849); however, the mean height was reduced to nearly half the reading in the bur and manual strip method. The disc group only showed a statistically significant decrease in surface roughness with polishing (P < 0.05). All other results were not significant. All methods of interproximal reduction do not influence enamel surface nanotopography significantly with and without polishing. Polishing resulted in significant reduction of surface roughness only in the disc group. [ABSTRACT FROM AUTHOR]

Introduction: Congenital or acquired bone defects in the oral and cranio-maxillofacial (OCMF) regions can seriously affect the normal function and facial appearance of patients, and cause great harm to their physical and mental health. To achieve good bone defect repair results, the prosthesis requires good osteogenic ability, appropriate porosity, and precise three-dimensional shape. Tantalum (Ta) has better mechanical properties, osteogenic ability, and microstructure compared to Ti6Al4V, and has become a potential alternative material for bone repair. The bones in the OCMF region have unique shapes, and 3D printing technology is the preferred method for manufacturing personalized prosthesis with complex shapes and structures. The surface characteristics of materials, such as surface morphology, can affect the biological behavior of cells. Among them, nano-topographic surface modification can endow materials with unique surface properties such as wettability and large surface area, enhancing the adhesion of osteoblasts and thereby enhancing their osteogenic ability.Methods: This study used 3D-printed porous tantalum scaffolds, and constructed nano-topographic surface through hydrothermal treatment. Its osteogenic ability was verified through a series of in vitro and in vivo experiments.Results: The porous tantalum modified by nano-topographic surface can promote the proliferation and osteogenic differentiation of BMSCs, and accelerate the formation of new bone in the Angle of the mandible bone defect of rabbits.Discussion: It can be seen that 3D-printed nano-topographic surface modified porous tantalum has broad application prospects in the repair of OCMF bone defects.

Currently, biomineralization is widely used as a surface modification approach to obtain ideal material surfaces with complex hierarchical nanostructures, morphologies, unique biological functions, and categorized organizations. The fabrication of biomineralized coating for the surfaces of scaffolds, especially synthetic polymer scaffolds, can alter surface characteristics, provide a favorable microenvironment, release various bioactive substances, regulate the cellular behaviors of osteoblasts, and promote bone regeneration after implantation. However, the biomineralized coating fabricated by immersion in a simulated body fluid has the disadvantages of non-uniformity, instability, and limited capacity to act as an effective reservoir of bioactive ions for bone regeneration. In this study, in order to promote the osteoinductivity of 3D-printed PCL scaffolds, we optimized the surface biomineralization procedure by nano-topographical guidance. Compared with biomineralized coating constructed by the conventional method, the nano-topographically guided biomineralized coating possessed more mineral substances and firmly existed on the surface of scaffolds. Additionally, nano-topographically guided biomineralized coating possessed better protein adsorption and ion release capacities. To this end, the present work also demonstrated that nano-topographically guided biomineralized coating on the surface of 3D-printed PCL scaffolds can regulate the cellular behaviors of USCs, guide the osteogenic differentiation of USCs, and provide a biomimetic microenvironment for bone regeneration.

Electrotaxis, the directional migration of cells in a constant electric field, is important in regeneration, development, and wound healing. Electrotaxis has a slower response and a smaller dynamic range than guidance by other cues, suggesting that the mechanism of electrotaxis shares both similarities and differences with chemical-gradient-sensing pathways. We examine a mechanism centered on the excitable system consisting of cortical waves of biochemical signals coupled to cytoskeletal reorganization, which has been implicated in random cell motility. We use electro-fused giant Dictyostelium discoideum cells to decouple waves from cell motion and employ nanotopographic surfaces to limit wave dimensions and lifetimes. We demonstrate that wave propagation in these cells is guided by electric fields. The wave area and lifetime gradually increase in the first 10 min after an electric field is turned on, leading to more abundant and wider protrusions in the cell region nearest the cathode. The wave directions display ‘U-turn’ behavior upon field reversal, and this switch occurs more quickly on nanotopography. Our results suggest that electric fields guide cells by controlling waves of signal transduction and cytoskeletal activity, which underlie cellular protrusions. Whereas surface receptor occupancy triggers both rapid activation and slower polarization of signaling pathways, electric fields appear to act primarily on polarization, explaining why cells respond to electric fields more slowly than to other guidance cues.

Optical surfaces are required to have high form accuracy and smoothness. The form accuracy must be below 50 nm. Form accuracy is currently on the order of several tens of nanometers or less; however, further improvement is required. To improve form accuracy, compensation grinding is performed based on form measurement results. However, when the form error is small, a small periodical waviness occurs on the ground surface, which is known as nano-topography. This waviness cannot be compensated for using conventional compensation methods because the nano-topography distributions are not reproducible. A previous study showed that grinding conditions affect the spatial frequency of nano-topography. Therefore, in this study, optimum grinding conditions are estimated from the view point of nano-topography distributions, and the grinding conditions are compensated to optimize these distributions. [ABSTRACT FROM AUTHOR]

Understanding the mechanisms underlying cell-surface interaction is of fundamental importance for the rational design of scaffolds aiming at tissue engineering, tissue repair and neural regeneration applications. Here, we examined patterns of neuroblastoma cells cultured in three-dimensional polymeric scaffolds obtained by two-photon lithography. Because of the intrinsic resolution of the technique, the micrometric cylinders composing the scaffold have a lateral step size of ~200 nm, a surface roughness of around 20 nm, and large values of fractal dimension approaching 2.7. We found that cells in the scaffold assemble into separate groups with many elements per group. After cell wiring, we found that resulting networks exhibit high clustering, small path lengths, and small-world characteristics. These values of the topological characteristics of the network can potentially enhance the quality, quantity and density of information transported in the network compared to equivalent random graphs of the same size. This is one of the first direct observations of cells developing into 3D small-world networks in an artificial matrix.

Objective: To investigate the role and molecular mechanism of nano-topography induced MSC osteoblastic differen tia-tion. Methods: The nanotopography of the titanium surface was prepared by anodization. qRT -PCR been used analyzed osteoblastic related gene expression. RNA sequencing obtained transcriptome data and screened the results (P<0.05). Changes of gene expression in the osteoblastic-related signaling pathway were observed. Results: Nano-topography was constructed on the surfuce of titanium. Osteoblastic-related genes (alkaline phosphatase (ALP), osteopontin (OPN) and osteocalcin (OCN)) were up-regulated (vs.cells on flat Ti) by real-time quantitative PCR. By analyzing the RNA sequencing data of these gene-related osteoblastic signaling pathways, it was found that the related protein genes in Notch and Wnt non-canonical signaling pathways changed significantly. Conclusion: By analyzing the genes related to osteoblastic differentiation of BMSC and RNA sequencing data, it is shown that in the process of Nano-topography-induced BMSC differentiation, Nano-topography up-regulated Notch and non-canonical Wnt signaling pathways compare with the flat surfuce. Therefore, it exhibits a more excellent effect of promoting bone differentiation. [ABSTRACT FROM AUTHOR]

Nano- and micro-structuring of implantable materials constitute a promising approach to introduce mechanical contact guidance effect, drive cells colonization, as well as to prevent bacteria adhesion and biofilm aggregation, through antifouling topography. Accordingly, this paper aims to extend the application of e-beam surface texturing and nano-structuring to the beta titanium alloys, which are of great interest for biomedical implants because of the low Young modulus and the reduction of the stress shielding effect. The paper shows that surface texturing on the micro-scale (micro-grooves) is functional to a contact guidance effect on gingival fibroblasts. Moreover, nano-structuring, derived from the e-beam surface treatment, is effective to prevent microfouling. In fact, human fibroblasts were cultivated directly onto grooved specimens showing to sense the surface micro-structure thus spreading following the grooves’ orientation. Moreover, Staphylococcus aureus colonies adhesion was prevented by the nano-topographies in comparison to the mirror-polished control, thus demonstrating promising antifouling properties. Furthermore, the research goes into detail to understand the mechanism of microfouling prevention due to nano-topography and microstructure.

Nano-scale surface roughening of metallic bio-implants plays an important role in the clinical success of hard tissue reconstruction and replacement. In this study, the nano-topographical features of titanium-niobium-zirconium (TNZ) alloy surfaces were controlled by using the target-ion induced plasma sputtering (TIPS) technique to improve the in vitro osteoblastic response. The TIPS technique is a novel strategy for etching the surface of metallic bio-implants using bombardment of target metal cations, which were accelerated by an extremely high negative bias voltage applied to the substrates. The nano-topography of the TNZ surfaces was successfully controlled by modulating experimental variables (such as the ion etching energy and the type of substrate or target materials) of TIPS. As a result, various nanopatterns (size: 10–210 nm) were fabricated on the surface of the TNZ alloys. Compared with the control group, experimental groups with nanopattern widths of ≥130 nm (130 and 210 nm groups) exhibited superior cell adhesion, proliferation, and differentiation. Our findings demonstrate that TIPS is a promising technology that can impart excellent biological functions to the surface of metallic bio-implants.

Garima Bhardwaj, Thomas J Webster Department of Chemical Engineering, Northeastern University, Boston, MA, USA Background: The attachment and initial growth of bacteria on an implant surface dictates the progression of infection. Treatment often requires aggressive antibiotic use, which does not always work. To overcome the difficulties faced in systemic and local antibiotic delivery, scientists have forayed into using alternative techniques, which includes implant surface modifications that prevent initial bacterial adhesion, foreign body formation, and may offer a controlled inflammatory response.Objective: The current study focused on using electrophoretic deposition to treat titanium with a nanophase titanium dioxide surface texture to reduce bacterial adhesion and growth. Two distinct nanotopographies were analyzed, Ti-160, an antimicrobial surface designed to greatly reduce bacterial colonization, and Ti-120, an antimicrobial surface with a topography that upregulates osteoblast activity while reducing bacterial colonization; the number following Ti in the nomenclature represents the atomic force microscopy root-mean-square roughness value in nanometers.Results: There was a 95.6% reduction in Staphylococcus aureus (gram-positive bacteria) for the Ti-160-treated surfaces compared to the untreated titanium alloy controls. There was a 90.2% reduction in Pseudomonas aeruginosa (gram-negative bacteria) on Ti-160-treated surfaces compared to controls. For ampicillin-resistant Escherichia coli, there was an 81.1% reduction on the Ti-160-treated surfaces compared to controls. Similarly for surfaces treated with Ti-120, there was an 86.8% reduction in S. aureus, an 82.1% reduction in P. aeruginosa, and a 48.6% reduction in ampicillin-resistant E. coli. The Ti-120 also displayed a 120.7% increase at day 3 and a 168.7% increase at day 5 of osteoblast proliferation over standard titanium alloy control surfaces.Conclusion: Compared to untreated surfaces, Ti-160-treated titanium surfaces demonstrated a statistically significant 1 log reduction in S. aureus and P. aeruginosa, whereas Ti-120 provided an additional increase in osteoblast proliferation for up to 5 days, criteria, which should be further studied for a wide range of orthopedic applications. Keywords: nanotopography, infection, titanium dioxide, electrophoretic deposition

The biomedical applications of Mg-based alloys are limited by their rapid corrosion rate in the body fluid. In this study, the hydrothermal synthesis is employed to produce protective bioactive hydroxyapatite coating (HAC) and strontium-substituted hydroxyapatite coating (Sr-HAC) to further enhance the corrosion resistance and in vitro biocompatibility of biodegradable AZ91D Mg alloy in physiological environments. For comparison, the brucite Mg(OH)2 prepared by the alkaline pre-treatment is designated as a control group. Experimental evidences of XRD and XPS analysis confirm that Sr2+ ions can be incorporated into HA crystal structure. It is noted that the hydrothermally synthesized Sr-HAC conversion coating composed of a specific surface topography with the nanoscaled flake-like fine crystallites is constructed on the AZ91D Mg alloy. The hydrophilicity of Mg substrate is effectively enhanced with the decrease in static contact angles after performing alkaline and hydrothermal treatments. Potentiodynamic polarization measurements reveal that the nanostructured Sr-HAC-coated specimens exhibit superior corrosion resistance than HAC and alkaline pre-treated Mg(OH)2. Moreover, immersion tests demonstrate that Sr-HAC provides favorable long-term stability for the Mg alloy with decreasing concentration of released Mg2+ ions in the SBF and the reduced corrosion rate during the immersion length of 30 days. The cells cultured on Sr-HAC specimens exhibit higher viability than those on the alkaline-pre-treated Mg(OH)2 and HAC specimens. The Sr-substituted HA coating with a nanostructured surface topography can help to stimulate the cell viability of osteoblastic cells.

Abstract The 3-D spatial and mechanical features of nano-topography can create alternative environments, which influence cellular response. In this paper, murine fibroblast cells were grown on surfaces characterized by protruding nanotubes. Cells cultured on such nano-structured surface exhibit stronger cellular adhesion compared to control groups, but despite the fact that stronger adhesion is generally believed to promote cell cycle progression, the time cells spend in G1 phase is doubled. This apparent contradiction is solved by confocal microscopy analysis, which shows that the nano-topography inhibits actin stress fiber formation. In turn, this impairs RhoA activation, which is required to suppress the inhibition of cell cycle progression imposed by p21/p27. This finding suggests that the generation of stress fibers, required to impose the homeostatic intracellular tension, rather than cell adhesion/spreading is the limiting factor for cell cycle progression. Indeed, nano-topography could represent a unique tool to inhibit proliferation in adherent well-spread cells. Graphical abstract Nano-topography influences cell mechanotransduction, by inhibiting stress fiber, formation. The lack of stress fibers blocks the transmission of out-to-inside force from, adhesion points to actin cytoskeleton and, consequently, the achievement of the critical, tensional homeostasis, which is required for RhoA activation and RhoA-dependent, suppression of p21 levels and cell cycle progression. Unlabelled Image [ABSTRACT FROM AUTHOR]

Abstract: Topographical and mechanical cues are vital for cell fate, tissue development in vivo, and to mimic the native cell growth environment in vitro. To date, the combinatory effect of mechanical and topographical cues as not been thoroughly investigated. This study investigates the effect of PCL nanofiber alignment and hydrostatic pressure on stem cell differentiation for bone tissue regeneration. Bone marrow‐derived human mesenchymal stem cells were seeded onto standard tissue culture plastic and electrospun random and aligned nanofibers. These substrates were either cultured statically or subjected to intermittent hydrostatic pressure at 270 kPa, 1 Hz for 60 min daily over 21 days in osteogenic medium. Data revealed higher cell metabolic activities for all mechanically stimulated cell culture formats compared with non‐stimulated controls; and random fibers compared with aligned fibers. Fiber orientation influenced cell morphology and patterns of calcium deposition. Significant up‐regulation of Collagen‐I, ALP, and Runx‐2 were observed for random and aligned fibers following mechanical stimulation; highest levels of osteogenic markers were expressed when hydrostatic pressure was applied to random fibers. These results indicate that fiber alignment and hydrostatic pressure direct stem cell fate and are important stimulus for tissue regeneration. © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: A: 629–640, 2018. [ABSTRACT FROM AUTHOR]

In clinical applications, osseointegration is essential for the long-term stability of dental implants. Inspired by the hierarchical structure of natural bone, we applied the electrochemical etching (EC) technique to form a micro-nano structure on a titanium alloy (Ti6Al4V) substrate, called EC surface. Sand blasting and acid etching (SLA) and machined (M) methods were employed to generate micro and smooth textures, respectively, as the control groups. The surface topographies of the three substrates were characterized using scanning electron microscopy (SEM). Then, human osteoblast-like cells (MG63) were cultured on substrates, and adhesion, proliferation, morphology, alkaline phosphatase activity (ALP), and gene expression levels of Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), osteopontin (OPN), and type I collagen (COLIA 1) were analyzed. MG63 cells cultured on the EC Ti alloy substrates displayed better cell adhesion, significant proliferation, and a higher production level of ALP, gene expressions of RUNX2, OCN, OPN and COLIA 1 ( p < 0.01 or p < 0.05) compared with those of SLA and M substrates. These results indicate that the micro-nano structure fabricated by electrochemical etching method is beneficial for the biological functions of MG63 cells and may be a promising candidate in dental implants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 757-769, 2017. [ABSTRACT FROM AUTHOR]

Introduction: Congenital or acquired bone defects in the oral and cranio-maxillofacial (OCMF) regions can seriously affect the normal function and facial appearance of patients, and cause great harm to their physical and mental health. To achieve good bone defect repair results, the prosthesis requires good osteogenic ability, appropriate porosity, and precise three-dimensional shape. Tantalum (Ta) has better mechanical properties, osteogenic ability, and microstructure compared to Ti6Al4V, and has become a potential alternative material for bone repair. The bones in the OCMF region have unique shapes, and 3D printing technology is the preferred method for manufacturing personalized prosthesis with complex shapes and structures. The surface characteristics of materials, such as surface morphology, can affect the biological behavior of cells. Among them, nano-topographic surface modification can endow materials with unique surface properties such as wettability and large surface area, enhancing the adhesion of osteoblasts and thereby enhancing their osteogenic ability. Methods: This study used 3D-printed porous tantalum scaffolds, and constructed nano-topographic surface through hydrothermal treatment. Its osteogenic ability was verified through a series of in vitro and in vivo experiments. Results: The porous tantalum modified by nano-topographic surface can promote the proliferation and osteogenic differentiation of BMSCs, and accelerate the formation of new bone in the Angle of the mandible bone defect of rabbits. Discussion: It can be seen that 3D-printed nano-topographic surface modified porous tantalum has broad application prospects in the repair of OCMF bone defects., 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. The reviewer XZ declared a shared affiliation with the authors to the handling editor at the time of review., (Copyright © 2023 Zhang, Zhou, Liu, Chen, Wu, Zhang, Lin and Zhang.)

One of the determinant factors for successful bioengineering is to achieve appropriate nano-topography and three-dimensional substrate. In this research, polycaprolactone (PCL) nano-fibrous mat with different roughness modified with O plasma was fabricated via electrospinning. The purpose of this study was to evaluate the effect of plasma modification along with surface nano-topography of mats on the quality of human fibroblast (HDFs) and osteoblast cells (OSTs)-substrate interaction. Surface properties were studied using scanning electron microscopy (SEM), atomic force microscopy (AFM), contact angle, Fourier-transformation infrared spectroscopy. We evaluated mechanical properties of fabricated mats by tensile test. The viability and proliferation of HDFs and OSTs on the substrates were followed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT). Mineralization of the substrate was determined by alizarin red staining method and calcium content of OSTs was determined by calcium content kit. Cells morphology was studied by SEM analysis. The results revealed that the plasma-treated electrospun nano-fibrous substrate with higher roughness was an excellent designed substrate. A bioactive topography for stimulating proliferation of HDFs and OSTs is to accelerate the latter's differentiation time. Therefore, the PCL substrate with high density and major nano-topography were considered as a bio-functional and elegant bio-substrate for tissue regeneration applications. [ABSTRACT FROM AUTHOR]

A β-Ta nanocrystalline coating was engineered onto a Ti-6Al-4V substrate using a double cathode glow discharge technique to improve the corrosion resistance and bioactivity of this biomedical alloy. The new coating has a thickness of ~40 μm and exhibits a compact and homogeneous structure composed of equiaxed β-Ta grains with an average grain size of ~22 nm, which is well adhered on the substrate. Nanoindentation and scratch tests indicated that the β-Ta coating exhibited high hardness combined with good resistance to contact damage. The electrochemical behavior of the new coating was systematically investigated in Hank’s physiological solution at 37 °C. The results showed that the β-Ta coating exhibited a superior corrosion resistance as compared to uncoated Ti-6Al-4V and commercially pure tantalum, which was attributed to a stable passive film formed on the β-Ta coating. The in vitro bioactivity was studied by evaluating the apatite-forming capability of the coating after seven days of immersion in Hank’s physiological solution. The β-Ta coating showed a higher apatite-forming ability than both uncoated Ti-6Al-4V and commercially pure Ta, suggesting that the β-Ta coating has the potential to enhance functionality and increase longevity of orthopaedic implants. [ABSTRACT FROM AUTHOR]

Porous silicon is a nano material in which pores with different sizes, densities and depths are infiltrated in conventional silicon imparting it augmented properties including biodegradability, biocompatibility, photoluminescence. Here, we realized porous silicon substrates in which the pore size and the fractal dimension were varied over a significant range. We loaded the described substrates with a PtCl ( O , O ′ − acac )( DMSO ) antitumor drug and determined its release profile as a function of pore size over time up to 15 days. We observed that the efficacy of delivery augments with the pore size moving from small (∼ 8 nm, efficiency of delivery ∼ 0.2) to large (∼ 55 nm, efficiency of delivery ∼ 0.7). Then, we verified the adhesion of MCF-7 breast cancer cells on the described substrates with and without the administration of the antitumor drug. This permitted to decouple and understand the coincidental effects of nano-topography and a controlled dosage of drugs on cell adhesion and growth. While large pore sizes guarantee elevated drug dosages, large fractal dimensions boost cell adhesion on a surface. For the particular case of tumor cells and the delivery of an anti-tumor drug, substrates with a small fractal dimension and large pore size hamper cell growth. The competition between nano-topography and a controlled dosage of drugs may either accelerate or block the adhesion of cells on a nanostructured surface, for applications in tissue engineering, regenerative medicine, personalized lab-on-a-chips, and the rational design of implantable drug delivery systems. [ABSTRACT FROM AUTHOR]

The study and the comprehension of the mechanism of cell adhesion and cell interaction with a substrate is a key point when biology and medicine meet engineering. This is the case of several biomedical applications, from regenerative medicine and tissue engineering to lab on chip and many others, in which the realization of the appropriate artificial surface allows the control of cell adhesion and proliferation. In this context, we aimed to design and develop a fabrication method of mesoporous (MeP) silicon substrates, doped with gold nanoparticles, in which we combine the capability of porous surfaces to support cell adhesion with the SERS capabilities of gold nanoparticles, to understand the chemical mechanisms of cell/surface interaction. MeP Si surfaces were realized by anodization of a Si wafer, creating the device for cell adhesion and growth. Gold nanoparticles were deposited on porous silicon by an electroless technique. We thus obtained devices with superior SERS capabilities, whereby cell activity may be controlled using Raman spectroscopy. MCF-7 breast cancer cells were cultured on the described substrates and SERS maps revealing the different expression and distribution of adhesion molecules were obtained by Raman spectroscopic analyses. [ABSTRACT FROM AUTHOR]

It is well established that surface topography can affect cell functions. However, finding a reproducible and reliable method for regulating stem cell behavior is still under investigation. It has been shown that cell imprinted substrates contain micro- and nanoscale structures of the cell membrane that serve as hierarchical substrates, can successfully alter stem cell fate. This study investigated the effect of the overall cell shape by fabricating silicon wafers containing pit structure in the average size of spherical-like chondrocytes using photolithography technique. We also used chondrocyte cell line (C28/I2) with spindle-like shape to produce cell imprinted substrates. The effect of all substrates on the differentiation of adipose-derived mesenchymal stem cells (ADSCs) has been studied. The AFM and scanning electron microscopy images of the prepared substrates demonstrated that the desired shapes were successfully transferred to the substrates. Differentiation of ADSCs was investigated by immunostaining for mature chondrocyte marker, collagen II, and gene expression of collagen II, Sox9, and aggrecan markers. C28/I2 imprinted substrate could effectively enhanced chondrogenic differentiation compared to regular pit patterns on the wafer. It can be concluded that cell imprinted substrates can induce differentiation signals better than engineered lithographic substrates. The nanostructures on the cell-imprinted patterns play a crucial role in harnessing cell fate. Therefore, the patterns must include the nano-topographies to have reliable and reproducible engineered substrates., (© 2023 IOP Publishing Ltd.)

We have used swift heavy-ion beam based lithography to create patterned bio-functional surfaces on rutile TiO 2 single crystals. The applied lithography method generates a permanent and well defined periodic structure of micrometre sized square holes having nanostructured TiO 2 surfaces, presenting different physical and chemical properties compared to the surrounding rutile single crystal surface. On the patterned substrates selective binding of oligonucleotides molecules is possible at the surfaces of the holes. This immobilisation process is only being controlled by UV light exposure. The patterned transparent substrates are compatible with fluorescence detection techniques, are mechanically robust, have a high tolerance to extreme chemical and temperature environments, and apparently do not degrade after ten cycles of use. These qualities make the patterned TiO 2 substrates useful for potential biosensor applications. [ABSTRACT FROM AUTHOR]

Titanium implant osseointegration is dependent on the cellular response to surface modifications and coatings. Titania-enriched nanocomposite polymeric resin coatings were prepared through the application of advanced ultrafine powder coating technology. Their surfaces were readily modified to create nano-rough (<100 nm) surface nano-topographies that supported human embryonic palatal mesenchymal cell responses. Energy dispersive x-ray spectroscopy confirmed continuous and homogenous coatings with a similar composition and even distribution of titanium. Scanning electron microscopy (SEM) showed complex micro-topographies, and atomic force microscopy revealed intricate nanofeatures and surface roughness. Cell counts, mitochondrial enzyme activity reduction of yellow 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) to dark purple, SEM, and inverted fluorescence microscopy showed a marked increase in cell attachment, spreading, proliferation, and metabolic activity on the nanostructured surfaces. Reverse Transcription- Polymerase Chain Reaction (RT-PCR) analysis showed that type I collagen and Runx2 expression were induced, and Alizarin red staining showed that mineral deposits were abundant in the cell cultures grown on nanosurfaces. This enhancement in human mesenchymal cell attachment, growth, and osteogenesis were attributed to the nanosized surface topographies, roughness, and moderate wetting characteristics of the coatings. Their dimensional similarity to naturally occurring matrix proteins and crystals, coupled with their increased surface area for protein adsorption, may have facilitated the response. Therefore, this application of ultrafine powder coating technology affords highly biocompatible surfaces that can be readily modified to accentuate the cellular response. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 100A:2695-2709, 2012. [ABSTRACT FROM AUTHOR]

Titanium nitride surfaces with silver concentrations of TiN/4.6at%Ag, TiN/10.8at%Ag and TiN/16.7at%Ag were produced using magnetron deposition. Antimicrobial and topographic properties affecting the interactions of the surfaces with microorganisms were assessed using Pseudomonas aeruginosa (1 μm × 3 μm rod-shaped Gram-negative bacteria) and Staphylococcus aureus (1 μm coccus-shaped Gram-positive bacteria) with retention assays, live/dead staining, and strength of attachment measurements. Retention of P. aeruginosa on the surfaces increased with an increase in surface silver content, grain size and topography, but the cells were easily removed from the surface under water when a force was applied. S. aureus cells were retained in lower numbers, but once attached, cells were difficult to remove. S. aureus cells attached in increased numbers on surfaces with lower silver content and smaller dimension surface features. The modification of hard wearing surfaces by addition of silver increased the antimicrobial activity of the surface, but the spectrum of antimicrobial activity varied with the target cell and surface properties. This work demonstrates that a range of methods and cell types need to be tested against surfaces which either discourage cell colonization and/or are potentially antimicrobial since the novel surface properties produced may inadvertently select and give advantage to a particular cell species. This may, in turn, affect the predicted surface efficacy. [ABSTRACT FROM AUTHOR]

Abstract: We have used ordered anodic alumina membranes as masks to create large scale ordered arrays of either holes or chemical islands on silica. Regularly spaced holes were obtained by direct etching of silica/silicon or glass substrates through the membranes used as etching masks. To create an array of chemically functional islands, the membrane is first glued on the substrate using a soft polymer and subsequently the polymer is etched gently though the mask. Finally organo-silane molecules are deposited through the alumina/polymer hybrid mask and the mask is removed chemically leaving nanoislands on the substrate. We anticipate that this technique will be useful in future biological and biomedical applications. [Copyright &y& Elsevier]

Aims: To describe the early phases of healing at the alveolar ridge around dental implants placed into fresh extraction sockets and to study whether (i) the dimension of the socket and (ii) a new implant surface nano-topography may have any influence. Materials and Methods: Sixteen beagle dogs received 64 test (new surface) and control implants randomly placed at the distal socket of 3P3 and 4P4. The implant shoulder was levelled with the marginal buccal bone crest. Animals were sacrificed at 4 h, 1, 2, 4 and 8 weeks for histological examination. Results: Bone loss occurred at the buccal crest between the 4-h and 1-week healing intervals, being more pronounced at the third premolar site [vertical bone loss between day 0 and 8 weeks 1.1 (0.5) mm]. The corresponding loss at the fourth premolar site was 0.3 (0.5) mm. Test sites containing implants with discrete crystalline deposition nano-particles' surface exhibited less buccal bone resorption than control sites at 8 weeks. Conclusion: Dimensions of the socket influenced the process of wound healing of implants placed into fresh extraction sockets, with more bone loss in the narrower sockets; however, the implant surface nano-topography seemed to have a limited effect in the healing of this implant surgical protocol. [ABSTRACT FROM AUTHOR]

Understanding and controlling the mechanisms of cell adhesion to nanomaterials is essential in tissue engineering, regenerative medicine, the development of experimental models for the study of neurodegenerative diseases. Nonetheless, despite the great many of studies that have examined how cells interact with nanoscale surfaces, little is known about the temporal dimension of the process of adhesion. In a previous work, Decuzzi and Ferrari, by examining how the energy of a cell changes while binding to a nanoscale surface, determined a criterion to decide whether nanoroughness can either enhance or retard cell adhesion. While accurate, however their model template disregards the time variable. Here, starting from the work of Decuzzi and Ferrari, we have developed a mathematical model based on chemotaxis that describes how cells adhere to a nanorough surface over time. Relaxing the originating constraint of a fixed density of ligand molecules expressed by the cell membrane, we show that the strength of adhesion depends on time and that, for certain values of the model parameters, a cell can arrive to establish a stable adhesion to a substrate even if the process of binding is initially energetically unfavourable. We show that, for a cell-membrane stiffness of 10 k P a , an initial density of receptors of 500 b o n d s / μ m 2 , a specific and non-specific energy density of adhesion of 10 - 5 J / m 2 and 10 - 7 J / m 2 , and roughness in the low nanometer range, cell adhesion forces can be completely activated from few seconds to some tens of minutes from the initial contact with the surface. [ABSTRACT FROM AUTHOR]

Abstract: The adsorption of bovine serum albumin (BSA) on platinum surfaces with a root-mean-square roughness ranging from 1.49nm to 4.62nm was investigated using quartz crystal microbalance with dissipation (QCM-D). Two different BSA concentrations, 50μg/ml and 1mg/ml, were used, and the adsorption studies were complemented by monitoring the antibody interaction with the adsorbed BSA layer. The adsorption process was significantly influenced by the surface nano-roughness, and it was observed that the surface mass density of the adsorbed BSA layer is enhanced in a non-trivial way with the surface roughness. From a close examination of the energy dissipation vs. frequency shift plot obtained by the QCM-D technique, it was additionally observed that the BSA adsorption on the roughest surface is subject to several distinct adsorption phases revealing the presence of structural changes facilitated by the nano-rough surface morphology during the adsorption process. These changes were in particular noticeable for the adsorption at the low (50μg/ml) BSA concentration. The results confirm that the nano-rough surface morphology has a significant influence on both the BSA mass uptake and the functionality of the resulting protein layer. [Copyright &y& Elsevier]

Abstract: The potential energy of interaction between a microsphere and regular nano-topographies of varying shape and dimensions in 1:1 aqueous electrolyte is determined using the surface element integration (SEI) technique. The height and diameter of a square-lattice of cylindrical protruding and hollow asperities are varied to show the influence of these geometric parameters on the interaction energy. The simulation predicts that the nano-protrusions would decrease the energy barrier towards adhesion, which in turn would yield much larger deposition rates than predicted by the DLVO (Derjaguin–Landau–Verwey–Overbeek) theory for particles on smooth surfaces. In qualitative agreement with experimental observations, decreasing the radius of curvature of the protrusions results in lower energy barriers. Inversely, at 100mM the presence of nano-pits on a surface would increase the height of the energy barrier, thus hampering particle deposition. [Copyright &y& Elsevier]

Protein adsorption behavior on the surfaces of biomedical materials is highly related to the biocompatibility of the materials. In the past, numerous research reports were mainly focused on the effect of chemical components of a material's surface on protein adsorption. The effect of surface topography on protein adsorption, the topic of this review, has recently received keen interest. The influence of surface nano-topographic factors, including roughness, curvature and geometry, on protein adsorption as well as the protein adsorption behavior, such as the amount of protein adsorbed, the activity and morphology of adsorbed protein, is introduced. [ABSTRACT FROM AUTHOR]

Abstract: In the field of biomaterials surfaces, the ability of the atomic force microscope (AFM) to access the surface structure at unprecedented spatial (vertical and lateral) resolution, is helping in a better understanding on how topography affects the overall interaction of biological cells with the material surface. Since cells in a wide range of sizes are in contact with the biomaterial surface, a quantification of the surface structure in such a wide range of dimensional scales is needed. With the advent of the AFM, this can be routinely done in the lab. In this work, we show that even when it is clear that such a scale-dependent study is needed, AFM maps of the biomaterial surface taken at different scanning lengths are not completely consistent when they are taken at the same scanning resolution, as it is usually done: AFM images of different scanning areas have different point-to-point physical distances. We show that this effect influences the quantification of the average (R a) and rms (R q) roughness parameters determined at different length scales. This is the first time this inconsistency is reported and should be taken into account when roughness is measured in this way. Since differences will be in general in the range of nanometres, this is especially interesting for those processes involving the interaction of the biomaterial surface with small biocolloids as bacteria, while this effect should not represent any problems for larger animal cells. [Copyright &y& Elsevier]

Abstract: A novel approach was developed to form engineered, electrically viable, neuronal networks, consisting of ganglion-like clusters of neurons. In the present method, the clusters are formed as the cells migrate on low affinity substrate towards high affinity, lithographically defined carbon nanotube templates on which they adhere and assemble. Subsequently, the gangliated neurons send neurites to form interconnected networks with pre-designed geometry and graph connectivity. This process is distinct from previously reported formation of clusterized neural networks in which a network of linked neurons collapses via neuronal migration along the inter-neuron links. The template preparation method is based on photo-lithography, micro-contact printing and carbon nanotube chemical vapor deposition techniques. The present work provides a new approach to form complex, engineered, interconnected neuronal network with pre-designed geometry via engineering the self-assembly process of neurons. [Copyright &y& Elsevier]

In order for cells to react to topography, they must be able to sense shape. When considering nano-topography, these shapes are much smaller than the cell, but still strong responses to nano-topography have been seen. Filopodia, or microspikes, presented by cells at their leading edges are thought to be involved in gathering of special information. In order to investigate this, and to develop an understanding of what size of feature can be sensed by cells, morphological observation (electron and fluorescent microscopy) of fibroblasts reacting to nano-pits with 35, 75 and 120 nm diameters has been used in this study. The nano-pits are especially interesting because unlike many of the nanofeatures cited in the literature, they have no height for the cells to react to. The results showed that cell filopodia, and retraction fibres, interacted with all pit sizes, although direct interaction was hard to image on the 35 nm pits. This suggests that cells are extremely sensitive to their nanoevironment and that should be taken in to consideration when designing next-generation tissue engineering materials. We suggest that this may occur through nanocontact guidance as filopodia are moved over the pits. [Copyright &y& Elsevier]

Having the ability to control cell behaviour would be of great advantage in tissue engineering. One method of gaining control over cell adhesion, proliferation, guidance and differentiation is use of topography. Whilst it has be known for some time that cells can be guided by micro-topography, it is only recently becoming clear that cells will respond strongly to nano-scale topography. The fact that cells will take cues from their micro- and nano-environment suggests that the cells are in some way ‘spatially aware’. It is likely that cells probe the shape of their surroundings using filopodia, and that this initial filopodia/topography interaction may be critical to down-stream cell reactions to biomaterials, or indeed, the extracellular matrix. One intriguing question is how small a feature can cells sense? In order to investigate the limits of cell sensing, high-resolution scanning electron microscopy has been used to simultaneously view cell filopodia and 10 nm high nano-islands. Fluorescence microscopy has also been used to look at adhesion formation. The results showed distinct filopodial/nano-island interaction and changes in adhesion morphology. [Copyright &y& Elsevier]

It is well known that many cell types react strongly to micro-topography. It is rapidly becoming clear than cells will also react to nano-topography. Polymer demixing is a rapid and low-cost chemical method of producing nano-topography. This manuscript investigates human fibroblast response to 27 nm high nano-islands produced by polymer demixing. Cell spreading, cytoskeleton, focal adhesion and Rac localisation were studied. The results showed that an initial rapid adhesion and cytoskeletal formation on the islands at 4 days of culture gave way to poorly formed contacts and vimentin cytoskeleton at 30 days of culture. [Copyright &y& Elsevier]

Electrotaxis, the directional migration of cells in a constant electric field, is important in regeneration, development, and wound healing. Electrotaxis has a slower response and a smaller dynamic range than guidance by other cues, suggesting that the mechanism of electrotaxis shares both similarities and differences with chemical-gradient-sensing pathways. We examine a mechanism centered on the excitable system consisting of cortical waves of biochemical signals coupled to cytoskeletal reorganization, which has been implicated in random cell motility. We use electro-fused giant Dictyostelium discoideum cells to decouple waves from cell motion and employ nanotopographic surfaces to limit wave dimensions and lifetimes. We demonstrate that wave propagation in these cells is guided by electric fields. The wave area and lifetime gradually increase in the first 10 min after an electric field is turned on, leading to more abundant and wider protrusions in the cell region nearest the cathode. The wave directions display 'U-turn' behavior upon field reversal, and this switch occurs more quickly on nanotopography. Our results suggest that electric fields guide cells by controlling waves of signal transduction and cytoskeletal activity, which underlie cellular protrusions. Whereas surface receptor occupancy triggers both rapid activation and slower polarization of signaling pathways, electric fields appear to act primarily on polarization, explaining why cells respond to electric fields more slowly than to other guidance cues., Competing Interests: QY, YM, LC, MH, BA, AB, PD, JF, WL No competing interests declared, (© 2022, Yang et al.)

Nano-scale surface roughening of metallic bio-implants plays an important role in the clinical success of hard tissue reconstruction and replacement. In this study, the nano-topographical features of titanium-niobium-zirconium (TNZ) alloy surfaces were controlled by using the target-ion induced plasma sputtering (TIPS) technique to improve the in vitro osteoblastic response. The TIPS technique is a novel strategy for etching the surface of metallic bio-implants using bombardment of target metal cations, which were accelerated by an extremely high negative bias voltage applied to the substrates. The nano-topography of the TNZ surfaces was successfully controlled by modulating experimental variables (such as the ion etching energy and the type of substrate or target materials) of TIPS. As a result, various nanopatterns (size: 10–210 nm) were fabricated on the surface of the TNZ alloys. Compared with the control group, experimental groups with nanopattern widths of ≥130 nm (130 and 210 nm groups) exhibited superior cell adhesion, proliferation, and differentiation. Our findings demonstrate that TIPS is a promising technology that can impart excellent biological functions to the surface of metallic bio-implants. [ABSTRACT FROM AUTHOR]

Nano- and micro-structuring of implantable materials constitute a promising approach to introduce mechanical contact guidance effect, drive cells colonization, as well as to prevent bacteria adhesion and biofilm aggregation, through antifouling topography. Accordingly, this paper aims to extend the application of e-beam surface texturing and nano-structuring to the beta titanium alloys, which are of great interest for biomedical implants because of the low Young modulus and the reduction of the stress shielding effect. The paper shows that surface texturing on the micro-scale (micro-grooves) is functional to a contact guidance effect on gingival fibroblasts. Moreover, nano-structuring, derived from the e-beam surface treatment, is effective to prevent microfouling. In fact, human fibroblasts were cultivated directly onto grooved specimens showing to sense the surface micro-structure thus spreading following the grooves' orientation. Moreover, Staphylococcus aureus colonies adhesion was prevented by the nano-topographies in comparison to the mirror-polished control, thus demonstrating promising antifouling properties. Furthermore, the research goes into detail to understand the mechanism of microfouling prevention due to nano-topography and microstructure. [ABSTRACT FROM AUTHOR]