Preventing bacterial infections remains a primary concern for healthcare systems and patients. Polyurethane (PU) is widely used in various invasive medical devices, improving PU surfaces─particularly by reducing bacterial adhesion─a highly sought-after goal. This study explores the spray coating of PU-based medical devices with oxidized graphene-based materials (GBMox) as antibacterial agents, specifically oxidized graphene nanoplatelets (GNPox) and graphene oxide (GO). Different formulations, with and without PU as a coating binder, were investigated to assess the potential for tuning the coating based on the intended application. The resulting coatings were characterized in terms of morphology using Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM), along with wettability and stability analysis. Antibacterial activity was evaluated against Staphylococcus epidermidis, with GNPox-containing coatings reducing bacterial adhesion by up to 82%, with no effect from blood plasma proteins. In vitro biocompatibility was confirmed across all surfaces: human fibroblasts adhered and spread on coatings without PU, while coatings combining GNPox and PU retained the low cell adhesiveness typical of PU. Overall, GBMox coatings on PU enhance antibacterial performance, preserve biocompatibility, and enable tuning of the cell adhesion behavior. These coatings offer a promising antibiotic-free strategy for PU-based biomedical applications, and the spray coating method provides a simple, reproducible, and industrially scalable approach.
Atrx loss was recently ascertained as insufficient to drive pancreatic neuroendocrine tumour (PanNET) formation in mice islets. We have identified a preponderant role of Atrx in the endocrine dysfunction in a Rip-Cre;AtrxKO genetically engineered mouse model (GEMM). To validate the impact of a different Cre-driver line, we used similar methodologies and characterised the Pdx1-Cre;AtrxKO (P.AtrxKO) GEMM to search for PanNET formation and endocrine fitness disruption for a period of up to 24 months. Male and female mice presented different phenotypes. Compared to P.AtrxWT, P.AtrxHOM males were heavier during the entire study period, hyperglycaemic between 3 and 12 mo., and glucose intolerant only from 6 mo.; in contrast, P.AtrxHOM females started exhibiting increased weight gains later (after 6 mo.), but diabetes or glucose intolerance was detected by 3 mo. Overall, all studied mice were overweight or obese from early ages, which challenged the histopathological evaluation of the pancreas and liver, especially after 12 mo. Noteworthily, losing Atrx predisposed mice to an increase in intrapancreatic fatty infiltration (FI), peripancreatic fat deposition, and macrovesicular steatosis. As expected, no animal developed PanNETs. An obese diabetic GEMM of disrupted Atrx is presented as potentially useful for metabolic studies and as a putative candidate for inserting additional tumourigenic genetic events.
ATRX is a chromatin remodeller that maintains telomere homeostasis. Loss of ATRX is described in approximately 10% of pancreatic neuroendocrine tumours (PanNETs) and associated with poorer prognostic features. Here, we present a genetically engineered mouse model (GEMM) addressing the role of Atrx loss (AtrxKO) in pancreatic β cells, evaluating a large cohort of ageing mice (for up to 24 months (mo.)). Atrx loss did not cause PanNET formation but rather resulted in worsening of ageing-related pancreatic inflammation and endocrine dysfunction in the first year of life. Histopathological evaluation highlighted an exacerbated prevalence and intensity of pancreatic inflammation, ageing features, and hepatic steatosis in AtrxKO mice. Homozygous floxed mice presented hyperglycaemia, increased weights, and glucose intolerance after 6 months, but alterations in insulinaemia were not detected. Floxed individuals presented an improper growth of their pancreatic endocrine fraction that may explain such an endocrine imbalance. A pilot study of BRACO-19 administration to AtrxKO mice resulted in telomere instability, reinforcing the involvement of Atrx in the maintenance of β cell telomere homeostasis. Thereby, a non-obese dysglycaemic GEMM of disrupted Atrx is here presented as potentially useful for metabolic studies and putative candidate for inserting additional tumourigenic genetic events.
Catheter-related infections are a common worldwide health problem, highlighting the need for antimicrobial catheters. Here, antibacterial potential of graphene nanoplatelets (GNP) incorporated in the commonly used polymer for catheter manufacture—polyurethane (PU)—is investigated. Two strategies are explored: melt-blending, producing a composite, and dip coating, where a composite layer is deposited on top of PU. GNP with different lateral sizes and oxidation degrees—GNP-M5, GNP-M15, GNP-M5ox, GNP-M15ox—are applied in both strategies, and the antimicrobial potential towards Staphylococcus epidermidis of GNP dispersions and GNP-containing PU evaluated. As dispersions, oxidized and smaller GNP powders (GNP-M5ox) inhibit 74% bacteria growth at 128 µg/mL. As surfaces, GNP exposure strongly impacts their antimicrobial profile: GNP absence at the surface of composites yields no significant effects on bacteria, while by varying GNP: PU ratio and GNP concentration, coatings enhance GNP exposure, depicting an antimicrobial profile. Oxidized GNP-containing coatings induce higher antibacterial effect than non-oxidized forms, particularly with smaller GNPox, where a homogeneous layer of fused platelets is formed on PU, leading to 70% reduction in bacterial adhesion and 70% bacterial death. This pioneering work unravels how to turn a polymer clinically used to produce catheters into an antimicrobial surface, crucial to reducing risk of infection associated with catheterization.
Thrombosis and infection are the major problems associated with blood contact devices. Making use of graphene based materials (GBMs) outstanding mechanical strength and high area/thickness ratio, and by playing with GBM thickness, lateral size and oxidation degree, it is possible to design novel biomaterials with antibacterial, bio/hemocompatible and mechanically suitable properties. We have explored different conjugations of GBMs, polymers/matrices and production techniques according to the desired application [1]. GBM-containing biomaterials were designed towards two main biomedical applications: i) as antimicrobial composites and coatings for dialysis catheters [25]; and ii) mechanically reinforced hydrogels for vascular grafts [6]. Results highlight the importance of GBM exposure on the surface of the biomaterials in order to exert antimicrobial properties, with oxidized GBMs presenting better performance. The oxidation degree also seems to be a detrimental factor in the mechanical reinforcement of hydrogels. Poly(2-hydroxyethyl methacrylate) (pHEMA)/ graphene oxide composites stand out as biomaterial with antibacterial and anti-thrombogenic properties, revealing huge potential for load-bearing applications, including blood contact devices.
The authors wish to make the following corrections to this paper [...].
Implantable medical devices infection and consequent failure is a severe health issue, which can result from bacterial adhesion, growth, and subsequent biofilm formation at the implantation site. Graphene-based materials, namely graphene oxide (GO), have been described as potential antibacterial agents when immobilized and exposed in polymeric matrices. This work focuses on the development of antibacterial and biocompatible 3D fibrous scaffolds incorporating GO. Poly(ε-caprolactone) scaffolds were produced, with and without GO, using wet-spinning combined with additive manufacturing. Scaffolds with different GO loadings were evaluated regarding physical-chemical characterization, namely GO surface exposure, antibacterial properties, and ability to promote human cells adhesion. Antimicrobial properties were evaluated through live/dead assays performed with Gram-positive and Gram-negative bacteria. 2 h and 24 h adhesion assays revealed a time-dependent bactericidal effect in the presence of GO, with death rates of adherent S. epidermidis and E. coli reaching ~80% after 24 h of contact with scaffolds with the highest GO concentration. Human fibroblasts cultured for up to 14 days were able to adhere and spread over the fibers, independently of the presence of GO. Overall, this work demonstrates the potential of GO-containing fibrous scaffolds to be used as biomaterials that hinder bacterial infection, while allowing human cells adhesion.
Although graphene-based materials (GBMs) have been thoroughly explored, their use in antimicrobial surfaces is still a developing field. This review overviews the different methods for fabricating GBMs-containing surfaces (free-standing films, coatings or bulk composites) and their antibacterial properties. The difficulty in controlling the broad number of factors affecting interactions between GBMs and bacteria hampers the establishment of clear cause-effect relations. Nevertheless, it is clear that GBMs size, exposure, oxidation, as well as surface conductivity and roughness are the main surface features influencing the antimicrobial properties. Depending on the production method, GBMs basal planes and/or sharp edges are exposed, having a major impact on bacteria through electron transference, piercing of the membrane or pore formation, amongst others. Each of these effects leads to production of oxidative stress and/or bacterial membrane disruption and, consequently, to bacterial death. While oxidized graphene-containing surfaces are antimicrobial when either basal planes or sharp edges are exposed, graphene-containing surfaces are mainly effective when sharp edges are protruding, except for few studies showing effect due to graphene basal planes when coated over conductive materials. As such, this review enlightens and clarifies the surface features most strongly affecting bacteria, providing researchers the necessary tools to produce antibacterial GBMs-containing surfaces with tuned mechanisms of action.
Silicone rubber (SR) peritoneal dialysis (PD) catheters are prone to bacterial adhesion and biofllm formation, which contributes to development of infection and associated morbidity in PD patients. We herein evaluate whether surface immobilization of graphene nanoplatelets (GNP) provides antimicrobial properties to SR. Dip and spray coating were used to deposit a dispersion containing SR and GNP-M5 or its oxidized form (GNP-M5ox) on the surface of silicone. The antimicrobial effect of GNP exposure and oxidation towards Staphylococcus epidermidis was assessed. GNP was successfully exposed on the surface, and while dipping provided better adhesion of either GNP, spraying resulted in uniform and higher surface coverage. Spraying led to enhanced bacterial adhesion comparing to dip coated and uncoated SR, which are similar. However, independently of the technique, GNP-M5ox coatings induced higher bacterial death. As such, SR/GNP-M5ox coating performed by dipping revealed to be the most promising approach, preserving bacterial adhesion levels of silicone while increasing bacterial death to around 80%. For the first time, graphene-based materials antimicrobial activity was evaluated by quantification of bacterial adhesion and viability. The high antibacterial effect, associated with a stable and cytocompatible coating which does not delaminate from SR surface, demonstrates its potential use in silicone biomedical industry. (C) 2018 Elsevier Ltd. All rights reserved.
Infections and thrombus formation are major concerns for the success of blood‐contacting medical devices. Antimicrobial coatings based on antimicrobial peptides (AMPs) are described as promising strategies to fight biomaterial‐associated infections. However, their efficiency in the presence of plasma and their effect on platelets adhesion/activation, essential for blood contact applications, is not known. In this work, the AMP cecropin–melittin (CM) is covalently immobilized onto polyurethane (PU) films envisaging a coating for intravascular catheters. Immobilization is done by dip‐coating of a layer of gold nanoparticles (Au NPs) functionalized with NH 2 and COOH terminated polyethylene glycol (PEG). Surfaces characterized using scanning electron microscopy (SEM), X‐ray photoelectron spectroscopy (XPS), quartz crystal microbalance with dissipation (QCM‐D), and colorimetric assays reveal a stable and homogeneous coating distribution. CM coating significantly reduces Staphylococcus epidermidis adhesion to PU films (≈80% in PBS). Its bactericidal activity is not affected in the presence of 1% human plasma (hPlasma) proteins with 65% reduction on viable bacteria comparing to PU. Moreover, CM coating is able to prevent platelet adhesion/activation to PU films (≈95% in PBS). This effect is also observed when surfaces are precoated with hPlasma. Overall, the developed antimicrobial coating demonstrates great potential to prevent bacterial infections on PU devices without instigating platelet adhesion/activation.
This study reports on the development of nanocomposite foams, prepared by Pickering emulsion templating, with promising tailored-properties, simply tunable by their composition. The selected multi component monomer mixtures comprise acrylated epoxidized soybean oil (AESO), 1,6-hexanediol diacrylate (HDD) and divinylbenzene (DVB), chosen by their renewable-origin or resemblance to renewable ones, and above all due to their varying stiffness or crosslinking-ability. The Pickering water in -oil emulsions, after their fast stabilization using cyclohexane and acetylated bacterial cellulose, were used as templates for the polymeric foams production. These original materials were thermally stable up to approximately 320 degrees C, and had a Young's modulus varying between 3.41 and 1639 MPa, being the highest results prompted by the use of HDD or DVB. (C) 2017 Elsevier Ltd. All rights reserved.