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Bacterial infections related to medical devices can cause severe problems, whose solution requires in-depth understanding of the interactions between bacteria and surfaces. This work investigates the influence of surface physicochemistry on bacterial attachment and detachment under flow through both empirical and simulation studies. We employed polydimethylsiloxane (PDMS) substrates having different degrees of crosslinking as the model material and the extended Derjaguin − Landau − Verwey − Overbeek model as the simulation method. Experimentally, the different PDMS materials led to similar numbers of attached bacteria, which can be rationalized by the identical energy barriers simulated between bacteria and the different materials. However, different numbers of residual bacteria after detachment were observed, which was suggested by simulation that the detachment process is determined by the interfacial physicochemistry rather than the mechanical property of a material. This finding is further supported by analyzing the bacteria detachment from PDMS substrates from which non-crosslinked polymer chains had been removed: similar numbers of residual bacteria were found on the extracted PDMS substrates. The knowledge gained in this work can facilitate the projection of bacterial colonization on a given surface., Journal of Colloid and Interface Science, 622, ISSN:0021-9797, ISSN:1095-7103

Cell-based therapies for articular cartilage lesions are expensive and time-consuming; clearly, a one-step procedure to induce endogenous repair would have significant clinical benefits. Acellular heterogeneous granular hydrogels were explored for their injectability, cell-friendly cross-linking, and ability to promote migration, as well as to serve as a scaffold for depositing cartilage extracellular matrix. The hydrogels were prepared by mechanical sizing of bulk methacrylated hyaluronic acid (HAMA) and bulk HAMA incorporating sulfated HAMA (SHAMA). SHAMA's negative charges allowed for the retention of positively charged growth factors (GFs) (e.g., TGFB3 and PDGF-BB). Mixtures of HAMA and GF-loaded SHAMA microgels were annealed by enzymatic cross-linking, forming heterogeneous granular hydrogels with GF deposits. The addition of GF loaded sulfated microislands guided cell migration and enhanced chondrogenesis. Granular heterogeneous hydrogels showed increased matrix deposition and cartilage tissue maturation compared to bulk or homogeneous granular hydrogels. This advanced material provides an ideal 3D environment for guiding cell migration and differentiation into cartilage. Statement of significance: Acellular materials which promote regeneration are of great interest for repair of cartilage defects, and they are more cost- and time-effective compared to current cell-based therapies. Here we develop an injectable, granular hydrogel system which promotes cell migration from the surrounding tissue, facilitating endogenous repair. The hydrogel architecture and chemistry were optimized to increase cell migration and extracellular matrix deposition. The present study provides quantitative data on the effect of microgel size and chemical modification on cell migration, growth factor retention and tissue maturation., Acta Biomaterialia, 166, ISSN:1742-7061, ISSN:1878-7568

To better understand the impact of biomaterial mechanical properties and growth medium on bacterial adhesion and biofilm formation under flow, we investigated the biofilm formation ability of

To avoid excessive usage of antibiotics and antimicrobial agents, smart wound dressings permitting controlled drug release for treatment of bacterial infections are highly desired. In search of a sensitive stimulus to activate drug release under physiological conditions, we found that the glass transition temperature (

Broadband administration and overuse of conventional antibiotics contribute to antibiotic resistance, demanding for alternative strategies. Metal ions, among them gallium (Ga), gained increasing in...

Bacterial colonization poses significant health risks, such as infestation of surfaces in biomedical applications and clean water unavailability. If maintaining the surrounding water clean is a target, developing surfaces with strong bactericidal action, which is facilitated by bacterial access to the surface and mixing, can be a solution. On the other hand, if sustenance of a surface free of bacteria is the goal, developing surfaces with ultralow bacterial adhesion often suffices. Here we report a facile, scalable, and environmentally benign strategy that delivers customized surfaces for these challenges. For bactericidal action, nanostructures of inherently antibacterial ZnO, through simple immersion of zinc in hot water, are fabricated. The resulting nanostructured surface exhibits extreme bactericidal effectiveness (9250 cells cm–2 h–1) that eliminates bacteria in direct contact and also remotely through the action of reactive oxygen species. Remarkably, the remote bactericidal action is achieved without the need for any illumination, otherwise required in conventional approaches. As a result, ZnO nanostructures yield outstanding water disinfection of >99.98%, in the dark, by inactivating the bacteria within 3 h. Moreover, Zn2+ released to the aqueous medium from the nanostructured ZnO surface have a concentration of 0.73 ± 0.15 ppm, markedly below the legal limit for safe drinking water (5–6 ppm). The same nanostructures, when hydrophobized (through a water-based or fluorine-free spray process), exhibit strong bacterial repulsion, thus substantially reducing bacterial adhesion. Such environmentally benign and scalable methods showcase pathways toward inhibiting surface bacterial colonization. ISSN:1520-5045 ISSN:0888-5885

In the human body, cells in a tissue are exposed to signals derived from their specific extracellular matrix (ECM), such as architectural structure, mechanical properties, and chemical composition (proteins, growth factors). Research on biomaterials in tissue engineering and regenerative medicine aims to recreate such stimuli using engineered materials to induce a specific response of cells at the interface. Although traditional biomaterials design has been mostly limited to varying individual signals, increasing interest has arisen on combining several features in recent years to improve the mimicry of extracellular matrix properties. Tremendous progress in combinatorial surface modification exploiting, for example, topographical features or variations in mechanics combined with biochemical cues has enabled the identification of their key regulatory characteristics on various cell fate decisions. Gradients especially facilitated such research by enabling the investigation of combined continuous changes of different signals. Despite unravelling important synergies for cellular responses, challenges arise in terms of fabrication and characterization of multifunctional engineered materials. This review summarizes recent work on combinatorial surface modifications that aim to control biological responses. Modification and characterization methods for enhanced control over multifunctional material properties are highlighted and discussed. Thereby, this review deepens the understanding and knowledge of biomimetic combinatorial material modification, their challenges but especially their potential.

To control material-associated bacterial infections, understanding the underlying mechanisms of bacteria and surface interactions is essential. Here we focused on studying how material mechanical and chemical properties can impact bacterial adhesion, using polydimethylsiloxane (PDMS) as a model material. To this end, PDMS surfaces of different stiffness were coated with a 2 nm highly cross-linked PDMS-like polymer film to confer comparable surface chemistry, while retaining similar mechanical properties for coated and uncoated samples. The uncoated samples showed increased interfacial adhesion force with the decrease of Young's modulus, whereas the nanolayer deposition yielded a comparable adhesion force for all surfaces. The Gram negative strains Escherichia coli, its fimbriae mutants and Pseudomonas aeruginosa as well as the Gram positive strain Staphylococcus epidermidis were analysed for their adhesion on these surfaces. For each bacterial strain similar numbers were found on the coated surfaces of different PDMS species, whereas the numbers on the uncoated surfaces increased several fold with the decrease of material modulus. Similar adhesion behaviour was also observed for the negatively charged abiotic polystyrene beads of similar size to bacteria. These results strongly suggest that the interfacial chemistry of the PDMS rather than the material mechanical properties plays a critical role in bacterial adhesion.

To enable a rapid-acting antibacterial mechanism without the release of biocidal substances, TiO2 catalysts have been considered based on the generation of reactive oxygen species (ROS). Doping with dissimilar metals generates electron-hole pairs with narrow band gaps promoting the production of ROS. Here, plasma technology is investigated to deposit Ag nano islets on defective TiOx films, stabilized by plasma postoxidation suppressing Ag ion release. Importantly, ROS generation is maintained upon storage in the dark yet with diminishing efficacy; however, it can be restored by exposure to visible light. The rapid-acting antibacterial properties are found to strongly correlate with ROS generation, which can even be maintained by functionalization with hydrophobic plasma polymer films. The cytocompatible coatings offer promising applications for implants and other medical devices.

Stimuli-responsive nanocarriers based on lipid self-assemblies have the potential to provide targeted delivery of antimicrobial peptides, limiting their side effects while protecting them from degradation in the biological environments. In the present study, we design and characterize a simple pH-responsive antimicrobial nanomaterial, formed through the self-assembly of oleic acid (OA) with the human cathelicidin LL-37 as a model for an amphiphilic antimicrobial peptide. Colloidal transformations from core-shell cylindrical micelles with a cross-sectional diameter of ∼5.5 nm and a length of ∼23 nm at pH 7.0 to aggregates of branched threadlike micelles at pH 5.0 were detected using synchrotron small-angle X-ray scattering, cryogenic transmission electron microscopy, and dynamic light scattering. Biological in vitro assays using an Escherichia coli bacteria strain showed high antimicrobial activity of the positively charged LL-37/OA aggregates at pH 5.0, which was not caused by the pH conditions themselves. Contrary to that, negligible antimicrobial activity was observed at pH 7.0 for the negatively charged cylindrical micelles. The nanocarrier's ability to switch its biological activity "on" and "off" in response to changes in pH could be used to focus the antimicrobial peptides' action to areas of specific pH in the body. The presented findings contribute to the fundamental understanding of lipid-peptide self-assembly and may open up a promising strategy for designing simple pH-responsive delivery systems for antimicrobial peptides.

Molecular photoswitches that can reversibly change color upon irradiation are promising materials for applications in molecular actuation and photoresponsive materials. However, the fabrication of photochromic devices is limited to conventional approaches such as mold casting and spin-coating, which cannot fabricate complex structures. Reported here is the first photoresist for direct laser writing of photochromic 3D micro-objects via two-photon polymerization. The integration of photochromism into thiol-ene photo-clickable resins enables rapid two-photon laser processing of highly complex microstructures and facile postmodification using a series of donor-acceptor Stenhouse adduct (DASA) photoswitches with different excitation wavelengths. The versatility of thiol-ene photo-click reactions allows fine-tuning of the network structure and physical properties as well as the type and concentration of DASA. When exposed to visible light, these microstructures exhibit excellent photoresponsiveness and undergo reversible color-changing via photoisomerization. It is demonstrated that the fluorescence variations of DASAs can be used as a reporter of photoswitching and thermal recovery, allowing the reading of DASA-containing sub-micrometric structures in 3D. This work delivers a new approach for custom microfabrication of 3D photochromic objects with molecularly engineered color and responsiveness.

Wear particles of total joint replacements may lead to an inflammatory response driven by cells of the monocyte/macrophage lineage. Today, there is a general agreement that the continuous release of wear particles by the implant has a critical impact on periprosthetic osteolysis, which can eventually lead to aseptic loosening of the implant. The focus of this study lay on the determination of the polarization of macrophages (M0) toward the pro-inflammatory M1 phenotype or the anti-inflammatory M2-like phenotype upon exposure to differently sized TiO

The replacement of animal models for investigation of inflammation and wound healing has been advancing by means of in vitro skin equivalents with increasing levels of complexity. However, the current in vitro skin models still have a limited pre-clinical relevance due to their lack of immune cells. So far, few steps have been made towards the incorporation of immune cells into in vitro skin and the requirements for immunocompetent co-cultures remain unexplored. To establish suitable conditions for incorporating macrophages into skin models, we evaluated the effects of different media on primary keratinocytes, fibroblasts and macrophages. Skin maturation was affected by culture in macrophage medium, while macrophages showed reduced viability, altered cell morphology and decreased response to pro- and anti-inflammatory stimuli in skin differentiation media, both in 2D and 3D. The results indicate that immunocompetent skin models have specific, complex requirements for supporting an accurate detection of immune responses, which point at the identification of a suitable culture medium as a crucial pre-requisite for the development of physiologically relevant models.

Norovirus and Rotavirus are among the pathogens causing a large number of disease outbreaks due to contaminated water. These viruses are nanoscale particles that are difficult to remove by common filtration approaches which are based on physical size exclusion, and require adsorption-based filtration methods. This study reports the pH-responsive interactions of viruses with cationic-modified nanocellulose and demonstrates a filter material that adsorbs nanoscale viruses and can be regenerated by changing the solution's pH. The bacteria viruses Qbeta and MS2, with diameters below 30 nm but different surface properties, are used to evaluate the pH-dependency of the interactions and the filtration process. Small angle X-ray scattering, cryogenic transmission electron microscopy, and ζ-potential measurements are used to study the interactions and analyze changes in their nanostructure and surface properties of the virus upon adsorption. The virus removal capacity of the cationic cellulose-based aerogel filter is 99.9% for MS2 and 93.6% for Qbeta, at pH = 7.0; and desorption of mostly intact viruses occurs at pH = 3.0. The results contribute to the fundamental understanding of pH-triggered virus-nanocellulose self-assembly and can guide the design of sustainable and environmentally friendly adsorption-based virus filter materials as well as phage and virus-based materials.

Fibrosis and scar formation is a medical condition observed under various circumstances, ranging from skin wound healing to cardiac deterioration after myocardial infarction. Among other complex interdependent phases during wound healing, fibrosis is associated with an increased fibroblast to myofibroblast transition. A common hypothesis is that decreasing the pH of non-healing, alkaline wounds to a pH range of 6.0 to 6.5 increases healing rates. A new material-based strategy to change the pH by use of electronic ion pumps is here proposed. In contrast to passive acidic wound dressings limited by non-controlled delivery kinetics, the unique electronic ion pump design and operation enables a continuous regulation of pH by H+ delivery over prolonged durations. In an in vitro model, fibroblast to myofibroblast differentiation is attenuated by lowering the physiological pH to an acidic regime of 6.62 +/- 0.06. Compared to differentiated myofibroblasts in media at pH 7.4, gene and protein expression of fibrosis relevant markers alpha-smooth muscle actin and collagen 1 is significantly reduced. In conclusion, myofibroblast differentiation can be steered by controlling the pH of the cellular microenvironment by use of the electronic ion pump technology as new bioelectronic drug delivery devices. This technology opens up new therapeutic avenues to induce scar-free wound healing. (C) 2021 The Authors. Published by Elsevier Ltd. Funding Agencies|Novartis Foundation for Medical-Biological ResearchUK Research & Innovation (UKRI)Biotechnology and Biological Sciences Research Council (BBSRC) [18C144]; Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; VinnovaVinnova

Among nosocomial infections, materials associated infections are the most frequent and severe due to biofilm formation. To prevent bacterial colonization, understanding the underlying interaction between bacteria and surface is fundamental. Herein we focused on studying how material viscoelasticity and physicochemistry can influence bacterial adhesion, using polydimethylsiloxane (PDMS) as a model material. To delineate the impact caused by bulk material from interfacial physicochemical properties, a 2 nm PDMS-like polymer layer was coated onto PDMS surfaces of different stiffness to confer comparable surface chemical properties, while retaining similar viscoelasticity for coated and uncoated PDMS species. Although the uncoated samples displayed increasing interfacial adhesion force with the decreasing Young's modulus, the nanolayer coating ensured comparable forces independent of material stiffness. The Gram negative strains Escherichia coli and Pseudomonas aeruginosa and the Gram positive strain Staphylococcus epidermidis were found to adhere respectively in similar numbers on the coated surfaces of different PDMS species, whereas the amount on the uncoated surfaces increased several fold with the decreasing modulus. The similar adhesion behaviour was noticed for abiotic polystyrene beads of similar size to bacteria, demonstrating that the interfacial chemistry of the PDMS rather than the material viscoelasticity plays a crucial role in bacterial adhesion.

A new class of photoresist is described for direct laser writing of photoswitchable 3D microstructures. The material comprising off-stoichiometric thiol-ene photo-clickable resins enables rapid two-photon laser processing of highly complex structures and facile post-modification with photoswitches. The microstructures were functionalized with a series of donor-acceptor Stenhouse adducts (DASAs) photoswitches with different excitation wavelength. The versatility of thiol–ene photo-click reaction enabled fine-tuning of the network structure and physical properties as well as the type and concentration of DASA photoswitches. When exposed to visible light, these microstructures exhibit excellent photo-responsiveness and undergo reversible color-changing via photoisomerization of DASA moieties. We describe that the weak fluorescence of DASAs can be used as a reporter of photoswitching, color changes, and thermal recovery, allowing the reading of DASA-containing sub-micrometric structures in 3D. This work delivers a new approach for custom microfabrication of 3D photochromic objects with molecularly engineered color and responsiveness.

Wound monitoring is essential to tackle chronic complications at their infancy and thus objectively scrutinize any delay in the epithelization process. Since glucose in wound exudates is recognized as key bio-marker in wound monitoring, the development of a cost-efficient detection method for glucose would aid at tackling early-stage infections in wounds. For the first time, we present a novel platform for one-step synthesis of non-enzymatic, cost-efficient optical glucose sensors. These are based on complexes formed by the interactions between polyborates and ethanolamines. The complexes, synthesized by just heating a solution of boric acid and ethanolamines at 150 °C, were characterized using 13C-NMR, 1H-NMR, 11B-NMR, analytical ultracentrifugation and DFT. The results show that the complexes in solution are extremely small (hydrodynamic diameter of around 0.5 nm) and that the polyborates species interact with the ethanolamines via both moderate and weak hydrogen bondings. These complexes were then tested on glucose concentrations ranging from 0 to 10 mM, showing significant changes in the fluorescent emission between the glucose level expressed in an healable wound (5.0–7.6 mM) and a chronic one (0.3–1.0 mM). published

Polymer-derived ceramics (PDC) have recently gained increased interest in the field of bioceramics. Among PDC's, carbon-rich silicon oxycarbide ceramics (SiOC) possess good combined electrical and mechanical properties. Their durability in aggressive environments and proposed cytocompatibility makes them an attractive material for fabrication of bio-MEMS devices such as pacemaker electrodes. The aim of the present study is to demonstrate the remarkable mechanical and electrical properties, biological response of PDCs modified with titanium (Ti) and their potential for application as pacemaker electrodes. Therefore, a new type of SiOC modified with Ti fillers was synthesized via PDC route using a Pt-catalyzed hydrosilylation reaction. Preceramic green bodies were pyrolyzed at 1000 degrees C under an argon atmosphere to achieve amorphous ceramics. Electrical and mechanical characterization of SiCxO2(1-x)/TiOxCy ceramics revealed a maximum electrical conductivity of 10 S cm(-1) and a flexural strength of maximal 1 GPa, which is acceptable for pacemaker applications. Ti incorporation is found to be beneficial for enhancing the electrical conductivity of SiOC ceramics and the conductivity values were increased with Ti doping and reached a maximum for the composition with 30 wt % Ti precursor. Cytocompatibility was demonstrated for the PDC SiOC ceramics as well as SiOC ceramics modified with Ti fillers. Cytocompatibility was also demonstrated for SiTiOC20 electrodes under pacing conditions by monitoring of cells in an in vitro 3D environment. Collectively, these data demonstrate the great potential of polymer-derived SiOC ceramics to be used as pacemaker electrodes.

Biofouling on silicone implants causes serious complications such as fibrotic encapsulation, bacterial infection, and implant failure. Here we report the development of antifouling, antibacterial silicones through covalent grafting with a cell-membrane-inspired zwitterionic gel layer composed of 2-methacryolyl phosphorylcholine (MPC). To investigate how substrate properties influence cell adhesion, we cultured human-blood-derived macrophages and Escherichia coli on poly(dimethylsiloxane) (PDMS) and MPC gel surfaces with a range of 0.5–50 kPa in stiffness. Cells attach to glass, tissue culture polystyrene, and PDMS surfaces, but they fail to form stable adhesions on MPC gel surfaces due to their superhydrophilicity and resistance to biofouling. Cytokine secretion assays confirm that MPC gels have a much lower potential to trigger proinflammatory macrophage activation than PDMS. Finally, modification of the PDMS surface with a long-term stable hydrogel layer was achieved by the surface-initiated atom-transfer radical polymerization (SI-ATRP) of MPC and confirmed by the decrease in contact angle from 110 to 20° and the >70% decrease in the attachment of macrophages and bacteria. This study provides new insights into the design of antifouling and antibacterial interfaces to improve the long-term biocompatibility of medical implants., Langmuir, 35 (5), ISSN:0743-7463, ISSN:1520-5827

Resistance to antibiotics has posed a high demand for novel strategies to fight bacterial infections. Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics. However, their poor solubility in water and sensitivity to degradation has limited their application. Here, we report the design of a smart, pH-responsive antimicrobial nanobiocomposite material based on the AMP nisin and 2,2,6,6-tetramethyl-1-piperidinyloxyl-oxidized nanofibrillated cellulose (TONFC). Morphological transformations of the nanoscale structure of nisin functionalized-TONFC fibrils were discovered at pH values between 5.8 and 8.0 using small-angle X-ray scattering. Complementary ζ potential measurements indicate that electrostatic attractions between the negatively charged TONFC surface and the positively charged nisin molecules are responsible for the integration of nisin. Modification of the pH level or increasing the ionic strength reduces the nisin binding capacity of TONFC. Biological evaluation studies using a bioluminescence-based reporter strain of Bacillus subtilis and a clinically relevant strain of Staphylococcus aureus indicated a significantly higher antimicrobial activity of the TONFC-nisin biocomposite compared to the pure nisin against both strains under physiological pH and ionic strength conditions. The in-depth characterization of this new class of antimicrobial biocomposite material based on nanocellulose and nisin may guide the rational design of sustainable antimicrobial materials.

Using low pressure plasma polymerization, nano-scaled oxygen-rich plasma polymer films (CO) were deposited onto pristine silicon wafers as well as on nitrogen-containing plasma polymer (CN) model surfaces. We investigate the influence of the nature of the substrate as well as a potential sub-surface effect emerging from the buried CO/CN interface, just nanometers below the surface. X-ray Photoelectron Spectroscopy and Time-of-Flight Secondary Ion Mass Spectrometry revealed two important phenomena that occurred during the deposition of the terminal CO layer: (1) a strong degree of oxidation, already for 1 nm nominal thickness, and (2) a gradual transition in chemical composition between the two layers, clearly indicating that effectively a vertical chemical gradient results, even when a two-step coating process was applied. Such terminal gradient film structures were used to study film stability in aqueous environments. Molecular rearrangements were scrutinized in the top-surface in contact with water and we found that the top-surface chemistry and wetting properties of the oxygen-rich termination layer matched those of thick CO reference coatings. Nevertheless, the adsorption of green fluorescent protein (GFP) was observed to be sensitive to the CO terminal layer thickness. Namely, an enhanced protein adsorption was observed for 1–2 nm thick CO layers on CN, whereas a significantly reduced protein adsorption was seen on ≥ 3 nm thick CO terminal layers. We conclude that both, surface and sub-surface conditions significantly affect protein adsorption as opposed to the traditional consideration of surface properties alone.

Advancements in the design of mechanical blood circulatory devices have greatly improved patient survival rates, but currently employed metals still provoke a thrombosis response upon contact with blood, with potential life-threatening consequences. While coating strategies have been developed to address this limitation, they possess inherent drawbacks such as susceptibility to crack formation and delamination. Herein, an amorphous metal based on palladium (Pd) is scrutinized and reveals substantial thrombogenic resistance compared to a state-of-the-art titanium alloy. In vitro assessment with human whole blood shows that the Pd glass provokes reduced platelet activation (lower expression of CD62P, CD41/CD61) and greatly retarded fibrin formation, but pronounced platelet spreading therewith challenging the dogma that platelet spreading equals activation. Mechanistic analysis of the early biomaterial–blood interactions reveals that conformational changes of adhered fibrinogen, and modified αIIbβ3 integrin expression and distribution across adhered platelets, underlay the superior performance of Pd glass. The study is accompanied by structural and thermophysical bulk investigations and physicochemical surface characterization to link the materials properties with the observed blood response. The results reveal a remarkable potential of Pd-based glass as direct blood-contacting bulk material without the need for coating., Advanced Functional Materials, 32 (4), ISSN:1616-3028, ISSN:1616-301X

Titanium (Ti)-based implants are broadly applied in the medical field, but their related infections can lead to implant failure. Photo-irradiation of metal materials to generate antimicrobial agents, an alternative to antibiotics, is a promising method to reduce bacterial infection and antibiotic usage. It is therefore important to understand how bacterial pathogens respond to Ti surfaces. Here, Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus, the most prevalent pathogens linked to healthcare-associated infections, were used as model strains. Two different kinds of Ti surfaces respectively stored in dry condition and 0.9 % NaCl solution were applied. Upon UV irradiation and in the absence of bacteria, both tested surfaces exhibited similar bactericidal activity, even though the surfaces stored in 0.9 % NaCl solution generated a slightly higher level of reactive oxygen species (ROS). Interestingly, P. aeruginosa and S. aureus responded to the irradiated Ti surfaces differently regarding interaction time: the number of viable P. aeruginosa was reduced up to 90 % after 30 min interaction with the treated surfaces compared to the untreated ones, but this reduction is lessened to 69 %–81 % after 240 min. By contrast, UV treatment of surfaces did not impact the viability of S. aureus after 30 min interaction, however, led to more than 99 % reduction after 240 min incubation. These results provide first experimental evidence that Gram negative and positive bacterial species respond to ROS with different inactivation kinetics. This work also demonstrated that treatment with photo-irradiation in the absence of bacteria conferred Ti surfaces with efficient bactericidal activity.

Pyranine is a non-toxic fluorescent dye, with a broad range of applications in biomedicine where it allows precise ratiometric detection of pH within the physiological pH window. Hereby, the facile synthesis, potentially interesting for commercial applications, of a novel ion pair between pyranine and benzalkonium is described. Benzalkonium, a quaternary ammonium salt with potent antimicrobial properties, makes pyranine sufficiently hydrophobic to allow its incorporation in conventional membranes and commercial wound dressings while maintaining its pH sensing performance unaffected and conferring the resulting ion pair strong antimicrobial properties. In conclusion, this novel fluorescent ion pair could be extremely promising for the non-invasive monitoring of wound pH.

Bi-functional micro-patterned plasma polymer films were prepared by first depositing a full-area amino-containing plasma polymer film (PPF) onto a substrate, followed by the deposition of a patterned oxygen-containing PPF via a polymeric mesh used as contact mask. As a result, an ultrathin film with alternating areas of amine and oxygen-containing groups is obtained. Such micro-patterns bear potential as templates for multi-sensitive bio-sensor substrates. The chemical surface composition is assessed using XPS and ToF-SIMS. On the masked amino-rich area a lateral chemical micro gradient was observed due to mesh mask shadowing. Stability of the coating was investigated over time in ambient air and in water, showing that the surface properties were maintained after 7 days in air and 1 day in water. To demonstrate functionality, the micro-patterned surface was exposed to a green fluorescent protein (GFP) and lateral resolution and selectivity during adsorption was studied. Keywords: Micro-patterned polymer films, Plasma deposition, Surface functionalization, Film characterization, Protein adsorption

Aging population and longer life expectancy are the main reasons for an increasing number of patients with wound problems. Although the interest in wound care increases continuously, wound management still remains a challenge mainly due to the higher occurrence of chronic wounds, which require intensive care and constant monitoring. Here, we demonstrate a fluorescent sensing system to monitor the wound status and to distinguish between an autonomously healing and a chronic wound at an early stage. The system allows monitoring two of the most relevant fluctuating wound parameters during the healing process which are pH and glucose concentration. A fluorescent pH indicator dye, carboxynaphthofluorescein, and a metabolite-sensing enzymatic system, based on glucose oxidase and horseradish peroxidase, were immobilized on a biocompatible polysaccharide matrix to develop a functional hydrogel coating for wound monitoring. The changes in metabolite and enzyme concentration in artificial wound extract were converted into a fluorescent signal.

Many promising antimicrobial materials fail to translate from bench to bedside, in part owing to a lack of in vitro biofilm models that can be used to predict their long-term in vivo antimicrobial and anti-biofilm activity. Various factors need to be considered for predictive modeling to mimic the conditions in vivo.

Among naturally occurring polymers, silk fibroin and sericin have attracted much attention in the field of tissue engineering; however, clinical application of silk fibroin/sericin scaffolds in a combined form has been questioned due to the possible pro-inflammatory reaction against native silk and fibroin/sericin 3D constructs. The objective of this study was to fabricate 3D spongy fibroin/sericin scaffolds and to explore the structural, biological and immunological properties of different ratios of fibroin and sericin. Structural characterization revealed a highly porous structure (>91%) with a large surface area and water uptake capacity for all different fibroin/sericin scaffolds. Notably, the scaffolds showed enhanced mechanical properties and a higher degradation rate with increasing sericin content. Excellent cell attachment and no significant cytotoxicity were observed in all scaffold types 7 days after seeding of osteoblast-like MG63 cells. Gene expression of pro-inflammatory markers TNF-α, CXCL10 and CD197 as well as TNF-α secretion by THP-1-derived macrophages revealed no significant immune response to all fibroin/sericin scaffold types when compared to sericin-free F1:S0 samples and a TCP (Mɸ) control group. These results demonstrate that spongy fibroin/sericin scaffolds are able to support the growth of osteoblast-like cells without eliciting a pro-inflammatory response, thus being a promising material for bone tissue engineering.

Implantation of temporary and permanent biomaterials in the body leads to a foreign body reaction (FBR), which may adversely affect tissue repair processes and functional integration of the biomaterial. However, modulation of the inflammatory response towards biomaterials can potentially enable a favorable healing response associated with functional tissue formation and tissue regeneration. In this work, incorporation of nicotinic acid in 3D silk scaffolds is explored as an immunomodulatory strategy for implantable biomaterials. Silk scaffolds were fabricated from dissolved Bombyx mori silk fibers by freeze-drying, resulting in silk scaffolds with high porosity (>94%), well-connected macropores, a high swelling degree (>550%) and resistance to in vitro degradation. Furthermore, drug-loaded scaffolds displayed a sustained drug release and excellent cytocompatibility could be observed with osteoblast-like MG63 cells. Cultivating M1-like macrophages on the scaffolds revealed that scaffolds loaded with nicotinic acid suppress gene expression of pro-inflammatory markers TNF-α, CXCL10 and CD197 as well as secretion of TNF-α in a concentration dependant manner. Hence, this study provides insights into the possible application of nicotinic acid in tissue engineering to control inflammatory responses towards biomaterials and potentially help minimizing FBR.

Achieving reproducibility in the 3D printing of biomaterials requires a robust polymer synthesis method to reduce batch-to-batch variation as well as methods to assure a thorough characterization throughout the manufacturing process. Particularly biomaterial inks containing large solid fractions such as ceramic particles, often required for bone tissue engineering applications, are prone to inhomogeneity originating from inadequate mixing or particle aggregation which can lead to inconsistent printing results. The production of such an ink for bone tissue engineering consisting of gellan gum methacrylate (GG-MA), hyaluronic acid methacrylate and hydroxyapatite (HAp) particles was therefore optimized in terms of GG-MA synthesis and ink preparation process, and the ink's printability was thoroughly characterized to assure homogeneous and reproducible printing results. A new buffer mediated synthesis method for GG-MA resulted in consistent degrees of substitution which allowed the creation of large 5 g batches. We found that both the new synthesis as well as cryomilling of the polymer components of the ink resulted in a decrease in viscosity from 113 kPa·s to 11.3 kPa·s at a shear rate of 0.1 s−1 but increased ink homogeneity. The ink homogeneity was assessed through thermogravimetric analysis and a newly developed extrusion force measurement setup. The ink displayed strong inter-layer adhesion between two printed ink layers as well as between a layer of ink with and a layer without HAp. The large polymer batch production along with the characterization of the ink during the manufacturing process allows ink production in the gram scale and could be used in applications such as the printing of osteochondral grafts.

Many materials used in the medical settings such as catheters and contact lenses as well as most biological tissues are not purely elastic, but rather viscoelastic. While substrate elasticity has been investigated for its influence on bacterial adhesion, the impact of substrate viscosity has not been explored. Here, the importance of considering substrate viscosity is explored by using polydimethylsiloxane (PDMS) as the substrate material, whose mechanical properties can be tuned from predominantly elastic to viscous by varying cross-linking degree. Interfacial rheology and atomic force microscopy analysis prove that PDMS with a low cross-linking degree exhibits both low stiffness and high viscosity. This degree of viscoelasticity confers to PDMS a remarkable stress relaxation, a good capability to deform and an increased adhesive force. Bacterial adhesion assays were conducted under flow conditions to study the impact of substrate viscosity on Escherichia coli adhesion. The viscous PDMS not only enhanced E. coli adhesion but also conferred greater resistance to desorption against shear stress at air/liquid interface, compared to the PDMS with high crosslinking degree. These findings highlight the importance to consider substrate viscosity while studying bacterial adhesion. The current work provides new insights to an improved understanding of how bacteria interact with complex viscoelastic environments., Journal of Colloid and Interface Science, 552, ISSN:0021-9797, ISSN:1095-7103

Despite major technological advances within the field of cardiovascular engineering, the risk of thromboembolic events on artificial surfaces in contact with blood remains a major challenge and limits the functionality of ventricular assist devices (VADs) during mid- or long-term therapy. Here, a biomimetic blood-material interface is created via a nanofiber-based approach that promotes the endothelialization capability of elastic silicone surfaces for next-generation VADs under elevated hemodynamic loads. A blend fiber membrane made of elastic polyurethane and low-thrombogenic poly(vinylidene fluoride- co-hexafluoropropylene) was partially embedded into the surface of silicone films. These blend membranes resist fundamental irreversible deformation of the internal structure and are stably attached to the surface, while also exhibiting enhanced antithrombotic properties when compared to bare silicone. The composite material supports the formation of a stable monolayer of endothelial cells within a pulsatile flow bioreactor, resembling the physiological in vivo situation in a VAD. The nanofiber surface modification concept thus presents a promising approach for the future design of advanced elastic composite materials that are particularly interesting for applications in contact with blood.

A true biomimetic of the cartilage extracellular matrix (ECM) could greatly contribute to our ability to regenerate this tissue in a mechanically demanding, often inflamed environment. Articular cartilage is a composite tissue made of cells and fibrillar proteins embedded in a hydrophilic polymeric meshwork. Here, a polyanionic functionalized alginate is used to mimic the glycosaminoglycan component of the native ECM. To create the fibrillar component, cryoelectrospinning of poly(e-caprolactone) on a −78 °C mandrel, subsequently treated by O2 plasma, is used to create a stable, ultraporous and hydrophillic nanofiber network. In this study, cell-laden, fiber-reinforced composite scaffolds thicker than 1.5 mm can be created by infiltrating a chondrocyte/alginate solution into the fiber mesh, which is then physically cross-linked. The fibrillar component significantly reinforces the chondroinductive, but mechanically weak sulfated alginate hydrogels. This allows the production of a glycosaminoglycan- and collagen type II-rich matrix by the chondrocytes as well as survival of the composite in vivo. To further enhance the system, the electrospun component is loaded with dexamethasone, which protected the cells from an IL-1β-mediated inflammatory insult.

Functional nanoparticles are valuable materials for energy production, bioelectronics, and diagnostic devices. The combination of biomolecules with nanosized material produces a new hybrid material with properties that can exceed the ones of the single components. Hematite is a widely available material that has found application in various sectors such as in sensing and solar energy production. We report a single-step immobilization process based on affinity and achieved by genetically engineering the protein of interest to carry a hematite-binding peptide. Fabricated hematite nanoparticles were then investigated for the immobilization of the two biomolecules C-phycocyanin (CPC) and laccase from Bacillus pumilus (LACC) under mild conditions. Genetic engineering of biomolecules with a hematite-affinity peptide led to a higher extent of protein immobilization and enhanced the catalytic activity of the enzyme.

The goal of this study was to evaluate human epiphyseal chondroprogenitor cells (ECPs) as a potential new cell source for cartilage regeneration. ECPs were compared to human bone marrow stromal cells (MSCs) and human adult articular chondrocytes (ACs) for their chondrogenic potential and phenotypic stability in vitro and in vivo. The cells were seeded in Optimaix-3D scaffolds at 5 × 104 cells/mm3 and gene expression, matrix production and mechanical properties were analysed up to 6 weeks. In vitro, ECPs synthesized consistently high collagen 2 and low collagen 10. AC-seeded constructs exhibited high donor variability in GAG/DNA values as well as in collagen 2 staining, but showed low collagen 10 production. MSCs, on the other hand, expressed high levels of collagen 2 but also of collagens 1 and 10, and were therefore not considered further. In vivo, there was considerable loss of matrix proteins in ECPs compared to in vitro cultured samples. To overcome this, a second implantation study investigated the effect of mixing cells with alginate prior to seeding in the scaffold. ECPs in alginate maintained their cartilage matrix and resisted mineralization and vessel infiltration better 6 weeks after subcutaneous implantation, whereas ACs lost their chondrogenic matrix completely. This study shows the great potential of ECPs as an off-the-shelf, highly chondrogenic cell type that produces stable cartilage in vivo. Copyright © 2016 John Wiley & Sons, Ltd.