The Controversial Effect of Antibiotics on Methicillin-Sensitive S. aureus: A Comparative In Vitro Study.

Methicillin-sensitive Staphylococcus (S.) aureus (MSSA) bacteremia remains a global challenge, despite the availability of antibiotics. Primary treatments include ß-lactam agents such as cefazolin and flucloxacillin. Ongoing discussions have focused on the potential synergistic effects of combining these agents with rifampicin or fosfomycin to combat infections associated with biofilm formation. Managing staphylococcal infections is challenging due to antibacterial resistance, biofilms, and S. aureus's ability to invade and replicate within host cells. Intracellular invasion shields the bacteria from antibacterial agents and the immune system, often leading to incomplete bacterial clearance and chronic infections. Additionally, S. aureus can assume a dormant phenotype, known as the small colony variant (SCV), further complicating eradication and promoting persistence. This study investigated the impact of antibiotic combinations on the persistence of S. aureus 6850 and its stable small colony variant (SCV strain JB1) focusing on intracellular survival and biofilm formation. The results from the wild-type strain 6850 demonstrate that ß-lactams combined with RIF effectively eliminated biofilms and intracellular bacteria but tend to select for SCVs in planktonic culture and host cells. Higher antibiotic concentrations were associated with an increase in the zeta potential of S. aureus, suggesting reduced membrane permeability to antimicrobials. When using the stable SCV mutant strain JB1, antibiotic combinations with rifampicin successfully cleared planktonic bacteria and biofilms but failed to eradicate intracellular bacteria. Given these findings, it is reasonable to report that ß-lactams combined with rifampicin represent the optimal treatment for MSSA bacteremia. However, caution is warranted when employing this treatment over an extended period, as it may elevate the risk of selecting for small colony variants (SCVs) and, consequently, promoting bacterial persistence.

Drug delivery of 6-bromoindirubin-3'-glycerol-oxime ether employing poly(D,L-lactide-co-glycolide)-based nanoencapsulation techniques with sustainable solvents.

BACKGROUND: Insufficient solubility and stability of bioactive small molecules as well as poor biocompatibility may cause low bioavailability and are common obstacles in drug development. One example of such problematic molecules is 6-bromoindirubin-3'-glycerol-oxime ether (6BIGOE), a hydrophobic indirubin derivative. 6BIGOE potently modulates the release of inflammatory cytokines and lipid mediators from isolated human monocytes through inhibition of glycogen synthase kinase-3 in a favorable fashion. However, 6BIGOE suffers from poor solubility and short half-lives in biological aqueous environment and exerts cytotoxic effects in various mammalian cells. In order to overcome the poor water solubility, instability and cytotoxicity of 6BIGOE, we applied encapsulation into poly(D,L-lactide-co-glycolide) (PLGA)-based nanoparticles by employing formulation methods using the sustainable solvents Cyrene™ or 400 g/mol poly(ethylene glycol) as suitable technology for efficient drug delivery of 6BIGOE. RESULTS: For all preparation techniques the physicochemical characterization of 6BIGOE-loaded nanoparticles revealed comparable crystallinity, sizes of about 230 nm with low polydispersity, negative zeta potentials around - 15 to - 25 mV, and biphasic release profiles over up to 24 h. Nanoparticles with improved cellular uptake and the ability to mask cytotoxic effects of 6BIGOE were obtained as shown in human monocytes over 48 h as well as in a shell-less hen's egg model. Intriguingly, encapsulation into these nanoparticles fully retains the anti-inflammatory properties of 6BIGOE, that is, favorable modulation of the release of inflammation-relevant cytokines and lipid mediators from human monocytes. CONCLUSIONS: Our formulation method of PLGA-based nanoparticles by applying sustainable, non-toxic solvents is a feasible nanotechnology that circumvents the poor bioavailability and biocompatibility of the cargo 6BIGOE. This technology yields favorable drug delivery systems for efficient interference with inflammatory processes, with improved pharmacotherapeutic potential.

Polystyrene Homopolymer Enhances Dispersion of MWCNTs Stabilized in Solution by a PS-b-P2VP Copolymer.

Block copolymers (BCPs) have previously been identified as powerful multiwalled carbon nanotube (MWCNT) dispersants in solution. However, relatively high costs and limited dispersibility hinder the use of BCPs in large-scale practical applications. Partial replacement of BCP with a low-cost homopolymer (HP) offers a promising approach to produce cost-effective MWNCT dispersions. The effect of HP/BCP blends on MWNCT dispersion degree and stability has yet to be elucidated. In this work, we tested the hypothesis that HP-induced BCP micelle size variation affects MWCNT dispersibility. Here, blends of the BCP poly(styrene)-block-poly(2-vinylpyridine) and the HP polystyrene (PS) were applied to examine BCP micelles' size dependence on the MWCNT dispersion degree. Light microscopy results showed that using HP/BCP blends, MWCNT dispersion was enhanced by up to 263% compared to pure BCP at a constant weight ratio of BCP to MWCNTs. Based on the correlation of increased MWCNT dispersion degree with increased BCP micelle size, as revealed by dynamic light scattering, an MWCNT dispersion mechanism is proposed. The mechanism includes a rationale for the unexpected finding that HP PS swells the BCP micelle's PS corona in a good solvent for PS. Using HP to increase MWCNT dispersion is a promising approach with possible applications in the production of high-performance composite materials. This holds especially for formulations of practical relevance where often (BCP) dispersants are only one of many components in the material.

Osteocytes Influence on Bone Matrix Integrity Affects Biomechanical Competence at Bone-Implant Interface of Bioactive-Coated Titanium Implants in Rat Tibiae.

Osseointegration is a prerequisite for the long-term success of implants. Titanium implants are preferred for their biocompatibility and mechanical properties. Nonetheless, the need for early and immediate loading requires enhancing these properties by adding bioactive coatings. In this preclinical study, extracellular matrix properties and cellular balance at the implant/bone interface was examined. Polyelectrolyte multilayers of chitosan and gelatin or with chitosan and Hyaluronic acid fabricated on titanium alloy using a layer-by-layer self-assembly process were compared with native titanium alloy. The study aimed to histologically evaluate bone parameters that correlate to the biomechanical anchorage enhancement resulted from bioactive coatings of titanium implants in a rat animal model. Superior collagen fiber arrangements and an increased number of active osteocytes reflected a significant improvement of bone matrix quality at the bone interface of the chitosan/gelatin-coated titan implants over chitosan/hyaluronic acid-coated and native implants. Furthermore, the numbers and localization of osteoblasts and osteoclasts in the reparative and remodeling phases suggested a better cellular balance in the chitosan/Gel-coated group over the other two groups. Investigating the micro-mechanical properties of bone tissue at the interface can elucidate detailed discrepancies between different promising bioactive coatings of titanium alloys to maximize their benefit in future medical applications.

How Nanotopography-Induced Conformational Changes of Fibrinogen Affect Platelet Adhesion and Activation.

The conformational state of adsorbed human plasma fibrinogen (HPF) has been recognized as the determinant factor in platelet adhesion and thrombus formation on blood-contacting biomaterials. Studies have highlighted the ability to control the HPF conformation merely by tailoring surface nanotopographical features. However, a clear relationship between the conformational changes of adsorbed HPF and the degree of platelet adhesion and activation achieved with different surface nanotopographies is still unclear. Here, we examined HPF assembly characteristics on nanostructured polybutene-1 (PB-1) surfaces with nanosized lamellar crystals (LCs), needle-like crystals (NLCs), and a nanostructured high-density polyethylene (HDPE) surface with shish-kebab crystals (SKCs), at a biologically relevant HPF concentration. By exposing the nanostructured surfaces with preadsorbed HPF to human platelets, significant differences in platelet response on LCs/SKCs and NLCs were identified. The former presented a uniform monolayer in the advanced stage of activation, whereas the latter exhibited minimal adhesion and the early stage of activation. Distinct platelet response was related to the postadsorption conformational changes in HPF, which were confirmed by topography-dependent shifts of the amide I band in attenuated total reflection-Fourier transform infrared (ATR-FTIR) analysis. Supported by atomic force microscopy (AFM) characterization, we propose that the mechanism behind the nanotopography-induced HPF conformation is driven by the interplay between the aspect ratios of polymeric crystals and HPF. From the biomedical perspective, our work reveals that surface structuring in a nanoscale size regime can provide a fine-tuning mechanism to manipulate HPF conformation, which can be exploited for the design of thromboresistant biomaterials surfaces.

The old sheep: a convenient and suitable model for senile osteopenia.

INTRODUCTION: Existing osteoporosis models in sheep exhibit some disadvantages, e.g., challenging surgical procedures, serious ethical concerns, failure of reliable induction of substantial bone loss, or lack of comparability to the human condition. This study aimed to compare bone morphological and mechanical properties of old and young sheep, and to evaluate the suitability of the old sheep as a model for senile osteopenia. MATERIALS AND METHODS: The lumbar vertebral body L3 of female merino sheep with two age ranges, i.e., old animals (6-10 years; n = 41) and young animals (2-4 years; n = 40), was analyzed concerning its morphological and mechanical properties by bone densitometry, quantitative histomorphometry, and biomechanical testing of the corticalis and/or central spongious region. RESULTS: In comparison with young sheep, old animals showed only marginally diminished bone mineral density of the vertebral bodies, but significantly decreased structural (bone volume, - 15.1%; ventral cortical thickness, - 11.8%; lateral cortical thickness, - 12.2%) and bone formation parameters (osteoid volume, osteoid surface, osteoid thickness, osteoblast surface, all - 100.0%), as well as significantly increased bone erosion (eroded surface, osteoclast surface). This resulted in numerically decreased biomechanical properties (compressive strength; - 6.4%). CONCLUSION: Old sheep may represent a suitable model of senile osteopenia with markedly diminished bone structure and formation, and substantially augmented bone erosion. The underlying physiological aging concept reduces challenging surgical procedures and ethical concerns and, due to complex alteration of different facets of bone turnover, may be well representative of the human condition.

MBEC Versus MBIC: the Lack of Differentiation between Biofilm Reducing and Inhibitory Effects as a Current Problem in Biofilm Methodology.

BACKGROUND: Biofilms are communities of aggregated, matrix-embedded microbial cells showing a high tolerance to an in principle adequate antibiotic therapy, often resulting in treatment failure. A major challenge in the management of biofilm-associated infections is the development of adequate, standardized biofilm susceptibility testing assays that are clinically meaningful, i.e. that their results correlate with treatment outcome. Different biofilm susceptibility endpoint parameters like the minimal biofilm eradication concentration (MBEC) or the minimal biofilm inhibitory concentration (MBIC) have been suggested as a guide for treatment of biofilm-associated infections, however with inconsistent perception and use among biofilm researchers, leading to confusion and contradictions among different anti-biofilm component studies and clinical trials. FINDINGS: Evaluation of anti-biofilm effects is mostly based on the untreated reference growth control biofilm measured at the same endpoint as the treated biofilm, neglecting the possible change of the untreated reference biofilm from the time point of pre-antimicrobial exposure to the measured endpoint. In this commentary, we point out the importance of individual quantification of mature, established biofilms before antimicrobial treatment for each biofilm model in order to draw conclusions on the measured biofilm effect size, i.e. biofilm reducing (MBEC) or biofilm inhibitory (MBIC) effects. CONCLUSION: The assessment of pre-treatment biofilms contributes to a standardized use of biofilm susceptibility endpoint parameters, which is urgently needed to improve the clinical validity of future anti-biofilm assays.

Nanoconfinement and Sansetsukon-like Nanocrawling Govern Fibrinogen Dynamics and Self-Assembly on Nanostructured Polymeric Surfaces.

Surface nanostructures are increasingly more employed for controlled protein assembly on functional nanodevices, in nanobiotechnology, and in nanobiomaterials. However, the mechanism and dynamics of how nanostructures induce order in the adsorbed protein assemblies are still enigmatic. Here, we use single-molecule mapping by accumulated probe trajectories and complementary atomic force microscopy to shed light on the dynamic of in situ assembly of human plasma fibrinogen (HPF) adsorbed on nanostructured polybutene-1 (PB-1) and nanostructured polyethylene (PE) surfaces. We found a distinct lateral heterogeneity of HPF-polymer nanostructure interface (surface occupancy, residence time, and diffusion coefficient) that allow identifying the interplay between protein topographical nanoconfinement, protein diffusion mechanism, and ordered protein self-assembly. The protein diffusion analysis revealed high-diffusion polarization without correlation to the anisotropic friction characteristic of the polymer surfaces. This suggests that HPF molecules confined on the nanosized PB-1 needle crystals and PE shish-kebab crystals, respectively, undergo partial detachment and diffuse via a Sansetsukon-like nanocrawling mechanism. This mechanism is based on the intrinsic flexibility of HPF in the coiled-coil regions. We conclude that nanostructured surfaces that encourage this characteristic surface mobility are more likely to lead to the formation of ordered protein assemblies and may be useful for advanced nanobiomaterials.

Nanocrystal Width Controls Fibrinogen Orientation and Assembly Kinetics on Poly(butene-1) Surfaces.

From the view of biomedical relevance, it is known that a specific arrangement of surface-immobilized human plasma fibrinogen (HPF) molecules is required to retain their biological functionality. Here, we demonstrate a topographical effect of chemically identical isotactic poly(butene-1) (iPB-1) semicrystalline nanostructures on the adsorption behavior, i.e., conformation change and orientation of HPF molecules. Using the distinct crystallization of iPB-1 under different shear conditions, polymer thin films consisting of needle-like crystals (NLCs) or shish-kebab crystals (SKCs) having lateral dimension, i.e., width, smaller than or comparable to the HPF major axis, respectively, were fabricated. The protein adsorption kinetic studies by quartz crystal microbalance with dissipation (QCM-D) revealed surface-dependent packing density and assembly configuration of HPF. High-resolution imaging disclosed a "side-on" protein adsorption and anisotropic network formation on the NLCs. With a 2-fold orientation analysis performed at both "single" protein and multiprotein levels, we quantitatively proved the preferential alignment of adsorbed HPF molecules with respect to the axial direction of the NLCs. Remarkably, the iPB-1 surface with SKCs perturbed the "end-to-end" protein-protein interactions and thus hindered the network formation. The distinguished adsorption behavior of HPF molecules on iPB-1 surfaces is explained by the physical effect of crystal width, which is additionally supported by the synergistic effect of crystal curvature and aspect ratio. Our studies provide fundamental insight into purely topography-controlled self-assembly of HPF molecules, which might be further exploited in creating topographically defined implant surfaces for preventing protein aggregation related disorders.

pH-Dependent Ordered Fibrinogen Adsorption on Polyethylene Single Crystals.

Nanostructured surfaces have the potential to influence the assembly as well as the orientation of adsorbed proteins and may, thus, strongly influence the biomaterials' performance. For the class of polymeric (bio)materials a reproducible and well-characterized nanostructure is the ordered chain folded surface of a polyethylene single crystal (PE-SC). We tested the hypothesis that the trinodal-rod-shaped protein human plasma fibrinogen (HPF) adsorbs on the (001) surface of PE-SCs along specific crystallographic directions. The PE-SC samples were prepared by isothermal crystallization in dilute solution and characterized by atomic force microscopy (AFM) before as well as after HPF adsorption at different concentrations and pH values. At a physiological pH of 7.4, connected HPF molecules, or e.g., fibrils, fibril networks, or sponge-like structures, were observed on PE-SC surfaces that featured no preferential orientation. The observation of these nonoriented multiprotein assemblies was explained by predominant protein-protein interactions and limited surface diffusion. However, at an increased pH of 9.2, single HPF molecules, e.g., spherical-shaped and trinodal-rod-shaped HPF molecules as well as agglomerates, were observed on the PE-SC surface. The presence of single HPF molecules at increased pH was explained by decreased protein-protein interactions. These single trinodal-rod-shaped HPF molecules oriented preferentially along crystallographic [100] and [010] directions on the PE-SC surface which was explained by an increased amount of intermolecular bonds along these crystallographic directions with increased surface atom density. The study established that HPF molecules can align on chemically homogeneous surface topographies one order of magnitude smaller than the dimension of the protein. This advances the understanding of how to control the assembly and orientation of proteins on nanostructured polymer surfaces. Controlled protein adsorption is a crucial key to improve the surface functionality of future implants and biosensors.

Antibacterial effect of silver (I) carbohydrate complexes on oral pathogenic key species in vitro.

BACKGROUND: It was the aim of this study to evaluate the antibacterial impact of two silver(I) carbohydrate complexes with tripodal thioglycosides, namely tris[2-(ß-D-thio-glucopyranosyl)ethyl]-amine-silver(I)-nitrate (3) and tris[2-(α-D-thio-manno-pyranosyl)ethyl]-amine-silver(I)-nitrate (4), on five oral pathogenic bacterial strains. Furthermore, cytocompatibility was tested using human gingival fibroblasts (HGF). METHODS: Minimum inhibitory concentrations (MIC) were determined on five oral pathogenic bacterial strains by using the broth microdilution method: Fusobacterium nucleatum (ATCC 10953), Aggregatibacter actinomycetemcomitans (ATCC 33384), Porphyromonas gingivalis (ATCC 33277), Streptococcus mutans (ATCC 25175) and Enterococcus faecalis (DSMZ 20376). Furthermore, antimicrobial efficiency was tested using agar diffusion assays. To evaluate cytocompatibility, human gingival fibroblasts (HGFs) were exposed to AgNO3 and complex 3 followed by a live/dead staining. RESULTS: MIC of the silver(I) complexes ranged between 0.625 and 5.0 mmol/L. The silver complexes 3 and 4 showed higher antibacterial efficiency against all tested species than AgNO3. Antibacterial efficiency of complexes 3 and 4 on F. nucleatum (≥18 mm) and A. actinomycetemcomitans (≥23 mm) was more pronounced than against P. gingivalis (≥15 mm). Complex 3 (20 mM) induced the largest inhibition zones (30 to 31 mm) on Gram-negative strains. For Gram-positive strains, the largest inhibition zones were achieved by complex 3 (20 mM/S. mutans: 28 mm, E. faecalis: 18 mm). Complex 3 had a lower cytotoxic impact on HGFs compared to AgNO3 by the power of ten. CONCLUSIONS: The findings suggest that silver(I) carbohydrate complexes 3 and 4 might function as novel antimicrobial agents for the treatment of periodontal, carious or endodontic diseases.

Enveloping self-assembly of carbon nanotubes at copolymer micelle cores.

Carbon nanotubes (CNTs) and their polymer nanocomposites are interesting materials for future applications, for example in optics or electronics. Research faces two major challenges with these outstanding nanofillers: control over dispersion and spatial arrangement within the nanocomposite, both required to achieve optimal structure and properties of CNT-based nanocomposites. We report on novel self-assembled multiwall CNT (MWCNT)/block copolymer (BCP) nanostructures realized by patterning MWCNTs with amphilphilic diblock copolymer micelles. A high molecular weight poly(styrene)-b-poly(2-vinylpyridine) BCP which forms large micelles (250 nm) was chosen to facilitate the templating by reducing the bending energy induced in the MWCNTs. We tested the hypothesis that it is possible to use an amphiphilic BCP as a dispersing agent and its spherical micelles as a template at the same time without modification of the CNTs. In thin films of the MWCNT/BCP micelles, highly separated MWCNTs were repeatedly observed which enveloped the core of the BCP micelles, i.e., the unfunctionalized MWCNTs segregated to the interface between the two BCP phases. Depending on the size of the MWCNTs, ring-like (split-ring) or network forming structures were obtained. The MWCNT templating mechanism, i.e., the segregation to the interface, is explained by the interfacial tension within the BCP interface and the chain entropy. The reported new complex nanocomposite has potential to be applied for example as cost-effective split-ring resonators for metamaterials or for conductive polymer films with an extremely low percolation threshold.

Discrimination between random and non-random processes in early bacterial colonization on biomaterial surfaces: application of point pattern analysis.

The dynamics of adhesion and growth of bacterial cells on biomaterial surfaces play an important role in the formation of biofilms. The surface properties of biomaterials have a major impact on cell adhesion processes, eg the random/non-cooperative adhesion of bacteria. In the present study, the spatial arrangement of Escherichia coli on different biomaterials is investigated in a time series during the first hours after exposure. The micrographs are analyzed via an image processing routine and the resulting point patterns are evaluated using second order statistics. Two main adhesion mechanisms can be identified: random adhesion and non-random processes. Comparison with an appropriate null-model quantifies the transition between the two processes with statistical significance. The fastest transition to non-random processes was found to occur after adhesion on PTFE for 2-3 h. Additionally, determination of cell and cluster parameters via image processing gives insight into surface influenced differences in bacterial micro-colony formation.

Effects of bone surface topography and chemistry on macrophage polarization.

Surface structure plays a crucial role in determining cell behavior on biomaterials, influencing cell adhesion, proliferation, differentiation, as well as immune cells and macrophage polarization. While grooves and ridges stimulate M2 polarization and pits and bumps promote M1 polarization, these structures do not accurately mimic the real bone surface. Consequently, the impact of mimicking bone surface topography on macrophage polarization remains unknown. Understanding the synergistic sequential roles of M1 and M2 macrophages in osteoimmunomodulation is crucial for effective bone tissue engineering. Thus, exploring the impact of bone surface microstructure mimicking biomaterials on macrophage polarization is critical. In this study, we aimed to sequentially activate M1 and M2 macrophages using Poly-L-Lactic acid (PLA) membranes with bone surface topographical features mimicked through the soft lithography technique. To mimic the bone surface topography, a bovine femur was used as a model surface, and the membranes were further modified with collagen type-I and hydroxyapatite to mimic the bone surface microenvironment. To determine the effect of these biomaterials on macrophage polarization, we conducted experimental analysis that contained estimating cytokine release profiles and characterizing cell morphology. Our results demonstrated the potential of the hydroxyapatite-deposited bone surface-mimicked PLA membranes to trigger sequential and synergistic M1 and M2 macrophage polarizations, suggesting their ability to achieve osteoimmunomodulatory macrophage polarization for bone tissue engineering applications. Although further experimental studies are required to completely investigate the osteoimmunomodulatory effects of these biomaterials, our results provide valuable insights into the potential advantages of biomaterials that mimic the complex microenvironment of bone surfaces.

The Effect of Stereocomplexation and Crystallinity on the Degradation of Polylactide Nanoparticles.

Polymeric nanoparticles (PNPs) are frequently researched and used in drug delivery. The degradation of PNPs is highly dependent on various properties, such as polymer chemical structure, size, crystallinity, and melting temperature. Hence, a precise understanding of PNP degradation behavior is essential for optimizing the system. This study focused on enzymatic hydrolysis as a degradation mechanism by investigation of the degradation of PNP with various crystallinities. The aliphatic polyester polylactide ([C3H4O2]n, PLA) was used as two chiral forms, poly l-lactide (PlLA) and poly d-lactide (PdLA), and formed a unique crystalline stereocomplex (SC). PNPs were prepared via a nanoprecipitation method. In order to further control the crystallinity and melting temperatures of the SC, the polymer poly(3-ethylglycolide) [C6H8O4]n (PEtGly) was synthesized. Our investigation shows that the PNP degradation can be controlled by various chemical structures, crystallinity and stereocomplexation. The influence of proteinase K on PNP degradation was also discussed in this research. AFM did not reveal any changes within the first 24 h but indicated accelerated degradation after 7 days when higher EtGly content was present, implying that lower crystallinity renders the particles more susceptible to hydrolysis. QCM-D exhibited reduced enzyme adsorption and a slower degradation rate in SC-PNPs with lower EtGly contents and higher crystallinities. A more in-depth analysis of the degradation process unveiled that QCM-D detected rapid degradation from the outset, whereas AFM exhibited delayed changes of degradation. The knowledge gained in this work is useful for the design and creation of advanced PNPs with enhanced structures and properties.

How Crystallographic Orientation-Induced Fibrinogen Conformation Affects Platelet Adhesion and Activation on TiO2.

Control of protein adsorption is essential for successful integration of healthcare materials into the body. Human plasma fibrinogen (HPF), especially its conformation is a key upstream regulator for platelet behavior and thus pathological clot formation at the blood-biomaterial interface. A previous study by the authors revealed that the conformation of adsorbed HPF can be controlled by rutile surface crystallographic orientation. Therefore, it is hypothesized that pre-adsorbed HPF on specific rutile orientation can regulate platelets adhesion and activation. Here, it is shown that platelets exposed to the four low index (110), (100), (101), (001) facets of TiO2 (rutile) exhibit surface-specific behavior. Scanning electron microscopy (SEM) observations of platelets morphology and P-selectin expression measurement revealed that on (110) facets, platelets adhesion and activation are suppressed. In contrast, extensive surface coverage by fully activated platelets is observed on (001) facets. Platelets' behavior has been linked to the HPF conformation and thereby availability of platelet-binding sequences. Atomic force microscopy (AFM) imaging supported by immunochemical analysis shows that on (110) facets, HPF is adsorbed in trinodular conformation rendering the γ400-411 platelet-binding sequence inaccessible. This research has potential implications on the bioactivity of different materials crystal facets, reducing the risk of pathological clot formation and thromboembolic complications.

Interfacial free energy driven nanophase separation in poly(3-hexylthiophene)/[6,6]-phenyl-C61-butyric acid methyl ester thin films.

The nanostructure of thermally annealed thin films of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) blends on hydrophobic and hydrophilic substrates was studied to unravel the relationship between the substrate properties and the phase structure of polymer blends in confined geometry. Indeed, the nature of the employed substrates was found to affect the extent of phase separation, the PCBM aggregation state and the texture of the whole system. In particular, annealing below the melting temperature of the polymer yielded the formation of PCBM nanometric crystallites on the hydrophobic substrates, while mostly amorphous microscopic aggregates were formed on the hydrophilic ones. Moreover, while an enhanced in-plane orientation of P3HT lamellae was promoted on hydrophobic substrates, a markedly tilted geometry was produced on the hydrophilic ones. The observed effects were interpreted in terms of a simple model connecting the interface free energy for the blend films to the different polymer chain mobility and diffusion velocity of PCBM molecules on the different substrates.

Antibacterial Designs for Implantable Medical Devices: Evolutions and Challenges.

The uses of implantable medical devices are safer and more common since sterilization methods and techniques were established a century ago; however, device-associated infections (DAIs) are still frequent and becoming a leading complication as the number of medical device implantations keeps increasing. This urges the world to develop instructive prevention and treatment strategies for DAIs, boosting the studies on the design of antibacterial surfaces. Every year, studies associated with DAIs yield thousands of publications, which here are categorized into four groups, i.e., antibacterial surfaces with long-term efficacy, cell-selective capability, tailored responsiveness, and immune-instructive actions. These innovations are promising in advancing the solution to DAIs; whereas most of these are normally quite preliminary "proof of concept" studies lacking exact clinical scopes. To help identify the flaws of our current antibacterial designs, clinical features of DAIs are highlighted. These include unpredictable onset, site-specific incidence, and possibly involving multiple and resistant pathogenic strains. The key point we delivered is antibacterial designs should meet the specific requirements of the primary functions defined by the "intended use" of an implantable medical device. This review intends to help comprehend the complex relationship between the device, pathogens, and the host, and figure out future directions for improving the quality of antibacterial designs and promoting clinical translations.

Rutile facet-dependent fibrinogen conformation: Why crystallographic orientation matters.

Previous studies implied that single crystalline rutile surfaces have the ability to guide the functionality of adsorbed blood plasma proteins. However, a clear relation between the rutile crystallographic orientation and conformation of adsorbed proteins is still missing. Here, we examine the adsorption characteristics of human plasma fibrinogen (HPF) on atomically flat single rutile crystals with (110), (100), (101) and (001) facets. By direct visualization of individual protein molecules through atomic force microscopy (AFM) imaging, the distinct conformations of HPF were determined depending on rutile surface crystallographic orientation. In particular, dominant trinodular and globular conformation was found on (110) and (001) facets, respectively. The observed variations of HPF conformation were reasoned from the surface water contact angle and surface energy point of view. By analyzing AFM-based force measurements, statistically significant changes in surface energies of rutile surfaces covered with HPF were determined and linked to HPF conformation. Furthermore, the facet-dependent structural rearrangement of HPF was indirectly confirmed through deconvolution of high-resolution X-ray photoelectron spectroscopy (XPS) carbon and nitrogen spectra. The globular, and thus native-like HPF conformation observed on (001) facet, was reflected in the lowest level of amino group formation. We propose that the mechanism behind the crystallographic orientation-induced HPF conformation is driven by the facet-specific surface hydrophilicity and energy. From the biomedical material perspective, our results demonstrate that the conformation of HPF can be guided by controlling the crystallographic orientation of the underlying material surface. This might be beneficial to the field of titanium-based biomaterials design and development.

Bone surface mimicked PDMS membranes stimulate osteoblasts and calcification of bone matrix.

Cellular microenvironments play a crucial role in cell behavior. In addition to the biochemical cues present in the microenvironments, biophysical and biomechanical properties on surfaces have an impact on cellular functionality and eventually cellular fate. Effects of surface topography on cell behavior are being studied extensively in the literature. However, these studies often try to replicate topographical features of tissue surfaces by using techniques such as chemical etching, photolithography, and electrospinning, which may result in the loss of crucial micro- and nano- features on the tissue surfaces such as bone. This study investigates the topographical effects of bone surface by transferring its surface features onto polydimethylsiloxane (PDMS) membranes using soft lithography from a bovine femur. Our results have shown that major features on bone surfaces were successfully transferred onto PDMS using soft lithography. Osteoblast proliferation and calcification of bone matrix have significantly increased along with osteoblast-specific differentiation and maturation markers such as osteocalcin (OSC), osterix (OSX), collagen type I alpha 1 chain (COL1A1), and alkaline phosphatase (ALP) on bone surface mimicked (BSM) PDMS membranes in addition to a unidirectional alignment of osteoblast cells compared to plain PDMS surfaces. This presented bone surface mimicking method can provide a versatile native-like platform for further investigation of intracellular pathways regarding osteoblast growth and differentiation.