Biocompatible Janus microparticle synthesis in a microfluidic device.

Janus particles are popular in recent years due to their anisotropic physical and chemical properties. Even though there are several established synthesis methods for Janus particles, microfluidics-based methods are convenient and reliable due to low reagent consumption, monodispersity of the resultant particles and efficient control over reaction conditions. In this work a simple droplet-based microfluidic technique is utilized to synthesize magnetically anisotropic TiO2-Fe2O3 Janus microparticles. Two droplets containing reagents for Janus particle were merged by using an asymmetric device such that the resulting droplet contained the constituents within its two hemispheres distinct from each other. The synthesized Janus particles were observed under the optical microscope and the scanning electron microscope. Moreover, a detailed in vitro characterization of these particles was completed, and it was shown that these particles have a potential use for biomedical applications.

Morphology of Nanostructured Tantalum Oxide Controls Stem Cell Differentiation and Improves Corrosion Behavior.

Tantalum is receiving increasing attention in the biomedical field due to its biocompatible nature and superior mechanical properties. However, the bioinert nature of tantalum still poses a challenge and limits its integration into the bone tissue. To address these issues, we fabricated nanotubular (NT), nanocoral (NC), and nanodimple morphologies on tantalum surfaces via anodization. The size of these nanofeatures was engineered to be approximately 30 nm for all anodized samples. Thus, the influence of the anodized nanostructured morphology on the chemical and biological properties of tantalum was evaluated. The NT and NC samples exhibited higher surface roughness, surface energy, and hydrophilicity compared to the nonanodized samples. In addition, the NT samples exhibited the highest corrosion resistance among all of the investigated samples. Biological experiments indicated that NT and NC samples promoted human adipose tissue-derived mesenchymal stem cell (hADMSC) spreading and proliferation up to 5 days in vitro. ALP, COL1A1, and OSC gene expressions as well as calcium mineral synthesis were upregulated on the NT and NC samples in the second and third weeks in vitro. These findings highlight the significance of nanostructured feature morphology for anodized tantalum, where the NT morphology was shown to be a potential candidate for orthopedic applications.

Synthesis of Anisotropic Magnetic Polymeric Janus Particles by In Situ Separation of Magnetic Nanoparticles in a Microfluidic Device.

Magnetic Janus particles have been studied extensively for medical and biological applications owing to their controllable mobility in fluid media. In this work, we report a novel microfluidic device designed for the synthesis of magnetically anisotropic Janus particles made of poly(ethylene glycol) diacrylate and embedded with magnetic iron oxide nanoparticles. Our method consists of a droplet generation step followed by magnetic separation using an external magnetic field and ultraviolet polymerization. The synthesized particles exhibit a monodisperse size distribution with a standard deviation of less than 3.5%, which is among the best size distributions obtained in the literature for magnetic Janus particles. The anisotropic magnetic property of the particles enable them to rotate about their own axes in the presence of an external magnetic field, introducing another degree of freedom to their motion. This microfluidic technique is simple, one-step, and versatile, offering control over the size distribution to synthesize magnetically anisotropic Janus particles.

Multifunctional Silk Fibroin/Carbon Nanofiber Scaffolds for In Vitro Cardiomyogenic Differentiation of Induced Pluripotent Stem Cells and Energy Harvesting from Simulated Cardiac Motion.

In this proof-of-concept study, cardiomyogenic differentiation of induced pluripotent stem cells (iPSCs) is combined with energy harvesting from simulated cardiac motion in vitro. To achieve this, silk fibroin (SF)-based porous scaffolds are designed to mimic the mechanical and physical properties of cardiac tissue and used as triboelectric nanogenerator (TENG) electrodes. The load-carrying mechanism, ß-sheet content, degradation characteristics, and iPSC interactions of the scaffolds are observed to be interrelated and regulated by their pore architecture. The SF scaffolds with a pore size of 379 ± 34 µm, a porosity of 79 ± 1%, and a pore interconnectivity of 67 ± 1% upregulated the expression of cardiac-specific gene markers TNNT2 and NKX2.5 from iPSCs. Incorporating carbon nanofibers (CNFs) enhances the elastic modulus of the scaffolds to 45 ± 3 kPa and results in an electrical conductivity of 0.021 ± 0.006 S/cm. The SF and SF/CNF scaffolds are used as conjugate TENG electrodes and generate a maximum power output of 0.37 × 10-3 mW/m2, with an open-circuit voltage and a short circuit current of 0.46 V and 4.5 nA, respectively, under simulated cardiac motion. A novel approach is demonstrated for fabricating scaffold-based cardiac patches that can serve as tissue scaffolds and simultaneously allow energy harvesting.

Antibacterial properties and osteoblast interactions of microfluidically synthesized chitosan - SPION composite nanoparticles.

In this research, a multi-step microfluidic reactor was used to fabricate chitosan - superparamagnetic iron oxide composite nanoparticles (Ch - SPIONs), where composite formation using chitosan was aimed to provide antibacterial property and nanoparticle stability for magnetic resonance imaging (MRI). Monodispersed Ch - SPIONs had an average particle size of 8.8 ± 1.2 nm with a magnetization value of 32.0 emu/g. Ch - SPIONs could be used as an MRI contrast agent by shortening T2 relaxation parameter of the surrounding environment, as measured on a 3 T MRI scanner. In addition, Ch - SPIONs with concentrations less than 1 g/L promoted bone cell (osteoblast) viability up to 7 days of culture in vitro in the presence of 0.4 T external static magnetic field. These nanoparticles were also tested against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), which are dangerous pathogens that cause infection in tissues and biomedical devices. Upon interaction of Ch - SPIONs with S. aureus and P. aeruginosa at 0.01 g/L concentration, nearly a 2-fold reduction in the number of colonies was observed for both bacteria strains at 48 h of culture. Results cumulatively showed that Ch - SPIONs were potential candidates as a cytocompatible and antibacterial agent that can be targeted to biofilm and imaged using an MRI.

3D Printing of Extracellular Matrix-Based Multicomponent, All-Natural, Highly Elastic, and Functional Materials toward Vascular Tissue Engineering.

3D printing offers an exciting opportunity to fabricate biological constructs with specific geometries, clinically relevant sizes, and functions for biomedical applications. However, successful application of 3D printing is limited by the narrow range of printable and bio-instructive materials. Multicomponent hydrogel bioinks present unique opportunities to create bio-instructive materials able to display high structural fidelity and fulfill the mechanical and functional requirements for in situ tissue engineering. Herein, 3D printable and perfusable multicomponent hydrogel constructs with high elasticity, self-recovery properties, excellent hydrodynamic performance, and improved bioactivity are reported. The materials' design strategy integrates fast gelation kinetics of sodium alginate (Alg), in situ crosslinking of tyramine-modified hyaluronic acid (HAT), and temperature-dependent self-assembly and biological functions of decellularized aorta (dAECM). Using extrusion-based printing approach, the capability to print the multicomponent hydrogel bioinks with high precision into a well-defined vascular constructs able to withstand flow and repetitive cyclic compressive loading, is demonstrated. Both in vitro and pre-clinical models are used to show the pro-angiogenic and anti-inflammatory properties of the multicomponent vascular constructs. This study presents a strategy to create new bioink whose functional properties are greater than the sum of their components and with potential applications in vascular tissue engineering and regenerative medicine.

Impregnation of polyethylene terephthalate (PET) grafts with BMP-2 loaded functional nanoparticles for reconstruction of anterior cruciate ligament.

Current artificial ligaments based on polyethylene terephthalate (PET) are associated with some disadvantages due to their hydrophobicity and low biocompatibility. In this study, we aimed to modify the surface of PET using polyethylene glycol (PEG)-terminated polystyrene (PS)-linoleic nanoparticles (PLinaS-g-PEG-NPs). We accomplished that BMP-2 in two different concentrations encapsulated in nanoparticles with an efficiency of 99.71 ± 1.5 and 99.95 ± 2.8%. While the dynamic contact angle of plain PET surface reduced from 116° to 115° after a measurement periods of 10 s, that of PLinaS-g-PEG-NPs modified PET from 80° to 17.5° within 0.35 s. According to in vitro BMP2 release study, BMP-2 was released 13.12 ± 1.76% and 45.47 ± 1.78% from 0.05 and 0.1BMP2-PLinaS-g-PEG-NPs modified PET at the end of 20 days, respectively. Findings from this study revealed that BMP2-PLinaS-g-PEG-NPs has a great potential to improve the artificial PET ligaments, and could be effectively applied for ACL reconstruction.

Anodized Nanostructured 316L Stainless Steel Enhances Osteoblast Functions and Exhibits Anti-Fouling Properties.

Poor osseointegration and infection are among the major challenges of 316L stainless steel (SS) implants in orthopedic applications. Surface modifications to obtain a nanostructured topography seem to be a promising method to enhance cellular interactions of 316L SS implants. In this study, arrays of nanodimples (NDs) having controlled feature sizes between 25 and 250 nm were obtained on 316L SS surfaces by anodic oxidation (anodization). Results demonstrated that the fabrication of NDs increased the surface area and, at the same time, altered the surface chemistry of 316L SS to provide chromium oxide- and hydroxide-rich surface oxide layers. In vitro experiments showed that ND surfaces promoted up to a 68% higher osteoblast viability on the fifth day of culture. Immunofluorescence images confirmed a well-spread cytoskeleton organization on the ND surfaces. In addition, higher alkaline phosphate activity and calcium mineral synthesis were observed on the ND surfaces compared to non-anodized 316L SS. Furthermore, a 71% reduction in Staphylococcus aureus (S. aureus) and a 58% reduction in Pseudomonas aeruginosa (P. aeruginosa) colonies were observed on the ND surfaces having a 200 nm feature size compared to non-anodized surfaces at 24 h of culture. Cumulatively, the results showed that a ND surface topography fabricated on 316L SS via anodization upregulated the osteoblast viability and functions while preventing S. aureus and P. aeruginosa biofilm synthesis.

Microfluidic Methods in Janus Particle Synthesis.

Janus particles have been at the center of attention over the years due to their asymmetric nature that makes them superior in many ways to conventional monophase particles. Several techniques have been reported for the synthesis of Janus particles; however, microfluidic-based techniques are by far the most popular due to their versatility, rapid prototyping, low reagent consumption and superior control over reaction conditions. In this review, we will go through microfluidic-based Janus particle synthesis techniques and highlight how recent advances have led to complex functionalities being imparted to the Janus particles.

Decellularized Bone Extracellular Matrix-Coated Electrospun PBAT Microfibrous Membranes with Cell Instructive Ability and Improved Bone Tissue Forming Capacity.

Current approaches to develop bone tissue engineering scaffolds have some limitations and shortcomings. They mainly suffer from combining mechanical stability and bioactivity on the same platform. Synthetic polymers are able to produce mechanically stable sturctures with fibrous morphology when they are electrospun, however, they cannot exhibit bioactivity, which is crucial for tissue engineering and regenerative medicine. One current strategy to bring bioactivity in synthetic materials is to combine extracellular matrix (ECM)-sourced materials with biologically inert synthetic materials. ECM-sourced materials without any modifications are mechanically unstable; therefore, reinforcing them with mechanically stable platforms is indispensable. In order to overcome this bifacial problem, we have demonstrated that poly(butylene adipate-co-terephthalate) (PBAT) electrospun microfibrous membranes can be successfully modified with decellularized bone ECM to endow fibers with bioactive hydrogel and mimic natural micro-features of the native bone tissue. The developed structures have been shown to support osteogenesis, confirmed by histochemical staining and gene expression studies. Furthermore, ECM-coated PBAT fibers, when they were aligned, supplied an improved level of osteogenesis. The strategy demonstrated can be adapted to any other tissues, and the emerging microfibrous, mechanically stable, and bioactive materials can find implications in the specific fields of tissue engineering and regenerative medicine.

Nanophase surface arrays on poly (lactic-co-glycolic acid) upregulate neural cell functions.

Nerve guidance channels (NGCs) promote cell-extracellular matrix (ECM) interactions occurring within the nanoscale. However, studies focusing on the effects of nanophase topography on neural cell functions are limited, and mostly concentrated on the sub-micron level (>100 nm) surface topography. Therefore, the aim of this study was to fabricate <100 nm sized structures on poly lactic-co-glycolic acid (PLGA) films used in NGC applications to assess the effects of nanophase topography on neural cell functions. For this purpose, nanopit surface arrays were fabricated on PLGA surfaces via replica molding method. The results showed that neural cell proliferation increased up to 65% and c-fos protein expression increased up to 76% on PLGA surfaces having nanophase surface arrays compared to the control samples. It was observed that neural cells spread to a greater extend and formed more neurite extensions on the nanoarrayed surfaces compared to the control samples. These results were correlated with increased hydrophilicity and roughness of the nanophase PLGA surfaces, and point toward the promise of using nanoarrayed surfaces in NGC applications.

Nanostructured Modifications of Titanium Surfaces Improve Vascular Regenerative Properties of Exosomes Derived from Mesenchymal Stem Cells: Preliminary In Vitro Results.

(1) Background: Implantation of metal-based scaffolds is a common procedure for treating several diseases. However, the success of the long-term application is limited by an insufficient endothelialization of the material surface. Nanostructured modifications of metal scaffolds represent a promising approach to faster biomaterial osteointegration through increasing of endothelial commitment of the mesenchymal stem cells (MSC). (2) Methods: Three different nanotubular Ti surfaces (TNs manufactured by electrochemical anodization with diameters of 25, 80, or 140 nm) were seeded with human MSCs (hMSCs) and their exosomes were isolated and tested with human umbilical vein endothelial cells (HUVECs) to assess whether TNs can influence the secretory functions of hMSCs and whether these in turn affect endothelial and osteogenic cell activities in vitro. (3) Results: The hMSCs adhered on all TNs and significantly expressed angiogenic-related factors after 7 days of culture when compared to untreated Ti substrates. Nanomodifications of Ti surfaces significantly improved the release of hMSCs exosomes, having dimensions below 100 nm and expressing CD63 and CD81 surface markers. These hMSC-derived exosomes were efficiently internalized by HUVECs, promoting their migration and differentiation. In addition, they selectively released a panel of miRNAs directly or indirectly related to angiogenesis. (4) Conclusions: Preconditioning of hMSCs on TNs induced elevated exosomes secretion that stimulated in vitro endothelial and cell activity, which might improve in vivo angiogenesis, supporting faster scaffold integration.

Osteogenic Properties of 3D-Printed Silica-Carbon-Calcite Composite Scaffolds: Novel Approach for Personalized Bone Tissue Regeneration.

Carbon enriched bioceramic (C-Bio) scaffolds have recently shown exceptional results in terms of their biological and mechanical properties. The present study aims at assessing the ability of the C-Bio scaffolds to affect the commitment of canine adipose-derived mesenchymal stem cells (cAD-MSCs) and investigating the influence of carbon on cell proliferation and osteogenic differentiation of cAD-MSCs in vitro. The commitment of cAD-MSCs to an osteoblastic phenotype has been evaluated by expression of several osteogenic markers using real-time PCR. Biocompatibility analyses through 3-(4,5-dimethyl- thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lactate dehydrogenase (LDH) activity, hemolysis assay, and Ames test demonstrated excellent biocompatibility of both materials. A significant increase in the extracellular alkaline phosphatase (ALP) activity and expression of runt-related transcription factor (RUNX), ALP, osterix (OSX), and receptor activator of nuclear factor kappa-Β ligand (RANKL) genes was observed in C-Bio scaffolds compared to those without carbon (Bio). Scanning electron microscopy (SEM) demonstrated excellent cell attachment on both material surfaces; however, the cellular layer on C-Bio fibers exhibited an apparent secretome activity. Based on our findings, graphene can improve cell adhesion, growth, and osteogenic differentiation of cAD-MSCs in vitro. This study proposed carbon as an additive for a novel three-dimensional (3D)-printable biocompatible scaffold which could become the key structural material for bone tissue reconstruction.

Development of electrically conductive porous silk fibroin/carbon nanofiber scaffolds.

Tissue engineering applications typically require three-dimensional scaffolds which provide the requisite surface area for cellular functions, while allowing transport of nutrients, waste and oxygen to and from the surrounding tissues. Scaffolds need to ensure sufficient mechanical properties to provide mechanically stable frameworks under physiologically relevant stress levels. Meanwhile, electrically conductive platforms are also desirable for the regeneration of specific tissues, where electrical impulses are transmitted throughout the tissue for proper physiological functioning. Towards this goal, carbon nanofibers (CNFs) were incorporated into silk fibroin (SF) scaffolds whose pore size and porosity were controlled during a salt leaching process. In our methodology, CNFs were dispersed in SF due to the hydrogen bond-forming ability of hexafluoro-2-propanol, a fluoroalcohol used as a solvent for SF. Results showed enhanced electrical conductivity and mechanical properties upon the incorporation of CNFs into the SF scaffolds, while the metabolic activities of cells cultured on SF/CNF nanocomposite scaffolds were significantly improved by optimizing the CNF content, porosity and pore size range of the scaffolds. Specifically, SF/CNF nanocomposite scaffolds with electrical conductivities as high as 0.023 S cm-1, tangent modulus values of 260 ± 30 kPa, a porosity as high as 78% and a pore size of 376 ± 53 µm were fabricated for the first time in the literature. Furthermore, an increase of about 34% in the wettability of SF was achieved by the incorporation of 10% CNF, which provided enhanced fibroblast spreading on scaffold surfaces.

Mineral-Doped Poly(L-lactide) Acid Scaffolds Enriched with Exosomes Improve Osteogenic Commitment of Human Adipose-Derived Mesenchymal Stem Cells.

Exosomes derived from mesenchymal stem cells are extracellular vesicles released to facilitate cell communication and function. Recently, polylactic acid (PLA), calcium silicates (CaSi), and dicalcium phosphate dihydrate (DCPD) have been used to produce bioresorbable functional mineral-doped porous scaffolds-through thermally induced phase separation technique, as materials for bone regeneration. The aim of this study was to investigate the effect of mineral-doped PLA-based porous scaffolds enriched with exosome vesicles (EVs) on osteogenic commitment of human adipose mesenchymal stem cells (hAD-MSCs). Two different mineral-doped scaffolds were produced: PLA-10CaSi-10DCPD and PLA-5CaSi-5DCPD. Scaffolds surface micromorphology was investigated by ESEM-EDX before and after 28 days immersion in simulated body fluid (HBSS). Exosomes were deposited on the surface of the scaffolds and the effect of exosome-enriched scaffolds on osteogenic commitment of hAD-MSCs cultured in proximity of the scaffolds has been evaluated by real time PCR. In addition, the biocompatibility was evaluated by direct-contact seeding hAD-MSCs on scaffolds surface-using MTT viability test. In both formulations, ESEM showed pores similar in shape (circular and elliptic) and size (from 10-30 µm diameter). The porosity of the scaffolds decreased after 28 days immersion in simulated body fluid. Mineral-doped scaffolds showed a dynamic surface and created a suitable bone-forming microenvironment. The presence of the mineral fillers increased the osteogenic commitment of hAD-MSCs. Exosomes were easily entrapped on the surface of the scaffolds and their presence improved gene expression of major markers of osteogenesis such as collagen type I, osteopontin, osteonectin, osteocalcin. The experimental scaffolds enriched with exosomes, in particular PLA-10CaSi-10DCPD, increased the osteogenic commitment of MSCs. In conclusion, the enrichment of bioresorbable functional scaffolds with exosomes is confirmed as a potential strategy to improve bone regeneration procedures.

Fabrication and cellular interactions of nanoporous tantalum oxide.

Tantalum possesses remarkable chemical and mechanical properties, and thus it is considered to be one of the next generation implant materials. However, the biological properties of tantalum remain to be improved for its use in tissue engineering applications. To enhance its cellular interactions, implants made of tantalum could be modified to obtain nanofeatured surfaces via the electrochemical anodization process. In this study, anodization parameters were adjusted to obtain a nanoporous surface morphology on tantalum surfaces and systematically altered to control the pore sizes from 25 to 65 nm using an aqueous HF:H2 SO4 electrolyte. Results indicated the formation of Ta2 O5 -based nanoporous surface layers, which had up to 28% more surface area and increased nanophase roughness (more than twofolds) compared to nonporous tantalum upon the anodization. It was observed that the nanoporous tantalum oxide surfaces promoted nearly 25% more fibroblast proliferation at 5 days in vitro and 15.5% more cellular spreading. Thus, nanoporous tantalum oxide surfaces can be used to increase biological interactions of the cells and provide a means of improving bioactivity of tantalum for biomaterial applications.

Comprehensive Evaluation of the Biological Properties of Surface-Modified Titanium Alloy Implants.

An increasing interest in the fabrication of implants made of titanium and its alloys results from their capacity to be integrated into the bone system. This integration is facilitated by different modifications of the implant surface. Here, we assessed the bioactivity of amorphous titania nanoporous and nanotubular coatings (TNTs), produced by electrochemical oxidation of Ti6Al4V orthopedic implants' surface. The chemical composition and microstructure of TNT layers was analyzed by X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). To increase their antimicrobial activity, TNT coatings were enriched with silver nanoparticles (AgNPs) with the chemical vapor deposition (CVD) method and tested against various bacterial and fungal strains for their ability to form a biofilm. The biointegrity and anti-inflammatory properties of these layers were assessed with the use of fibroblast, osteoblast, and macrophage cell lines. To assess and exclude potential genotoxicity issues of the fabricated systems, a mutation reversal test was performed (Ames Assay MPF, OECD TG 471), showing that none of the TNT coatings released mutagenic substances in long-term incubation experiments. The thorough analysis performed in this study indicates that the TNT5 and TNT5/AgNPs coatings (TNT5-the layer obtained upon applying a 5 V potential) present the most suitable physicochemical and biological properties for their potential use in the fabrication of implants for orthopedics. For this reason, their mechanical properties were measured to obtain full system characteristics.

Addition of Selenium Nanoparticles to Electrospun Silk Scaffold Improves the Mammalian Cell Activity While Reducing Bacterial Growth.

Silk possesses many beneficial wound healing properties, and electrospun scaffolds are especially applicable for skin applications, due to their smaller interstices and higher surface areas. However, purified silk promotes microbial growth. Selenium nanoparticles have shown excellent antibacterial properties and are a novel antimicrobial chemistry. Here, electrospun silk scaffolds were doped with selenium nanoparticles to impart antibacterial properties to the silk scaffolds. Results showed significantly improved bacterial inhibition and mild improvement in human dermal fibroblast metabolic activity. These results suggest that the addition of selenium nanoparticles to electrospun silk is a promising approach to improve wound healing with reduced infection, without relying on antibiotics.

Antimicrobial performance of mesoporous titania thin films: role of pore size, hydrophobicity, and antibiotic release.

Implant-associated infections are undesirable complications that might arise after implant surgery. If the infection is not prevented, it can lead to tremendous cost, trauma, and even life threatening conditions for the patient. Development of an implant coating loaded with antimicrobial substances would be an effective way to improve the success rate of implants. In this study, the in vitro efficacy of mesoporous titania thin films used as a novel antimicrobial release coating was evaluated. Mesoporous titania thin films with pore diameters of 4, 6, and 7 nm were synthesized using the evaporation-induced self-assembly method. The films were characterized and loaded with antimicrobial agents, including vancomycin, gentamicin, and daptomycin. Staphylococcus aureus and Pseudomonas aeruginosa were used to evaluate their effectiveness toward inhibiting bacterial colonization. Drug loading and delivery were studied using a quartz crystal microbalance with dissipation monitoring, which showed successful loading and release of the antibiotics from the surfaces. Results from counting bacterial colony-forming units showed reduced bacterial adhesion on the drug-loaded films. Interestingly, the presence of the pores alone had a desired effect on bacterial colonization, which can be attributed to the documented nanotopographical effect. In summary, this study provides significant promise for the use of mesoporous titania thin films for reducing implant infections.

Understanding the Role of Polymer Surface Nanoscale Topography on Inhibiting Bacteria Adhesion and Growth.

Catheter-associated infections, most of which are caused by microbial biofilms, are still a serious issue in healthcare and are associated with significant morbidity, mortality, and excessive medical costs. Currently, the use of nanostructured materials, especially materials with nanofeatured topographies, which have more surface area, altered surface energy, enhanced select protein adsorption, and selectively increased desirable cell functions while simultaneously decreasing competitive cell functions, seem to be among the most promising ways for reducing initial bacteria attachment, biofilm formation, and infections. In this study, polydimethylsiloxane (PDMS), a commonly used polymeric catheter material, was formulated to mimic the nanopatterned topography of natural tissue by using a template method with nanotubular anodized titanium. Results showed that increased PDMS surface nanoscale roughness alone can inhibit both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria adhesion and growth for up to 2 days, the time length of the current study. Additionally, increased fibroblast and endothelial cell adhesion on nano-PDMS indicated that this nanoscale topography had no toxic effects toward mammalian cells. Mechanistically, this study also developed a model for the first time to correlate bacteria responses to nanoscale roughness with initial protein and biomolecule adsorption (specifically, casein protein and glucose, which are unique biomolecules that mediate bacteria functions). Data revealed that the increase in nanoscale roughness and associated energy contributed to greater select casein adsorption during the first several minutes of culture, which is critical for decreasing bacteria attachment and growth. In contrast, no significant differences for glucose adsorption between samples before and after nanofabrication were identified. These results together indicated that the present biomimetic nanopatterned PDMS surface without any chemical or antibiotic modification has the potential to combat catheter-associated infections and should be further investigated.