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Polypropylene (PP) mesh is well-known as a gold standard of all prosthetic materials of choice for the reinforcement of soft tissues in case of hernia, organ prolapse, and urinary incontinence. The adverse effects that follow surgical mesh implantation remain an unmet medical challenge. Herein, it is outlined a new approach to allow viability and adhesion of human menstrual blood-derived mesenchymal stromal cells (MenSCs) on PP surgical meshes. A multilayered fibrin coating, based on fibrinogen and thrombin from a commercial fibrin sealant, was optimized to guarantee a homogeneous and stratified film on PP mesh. MenSCs were seeded on the optimized fibrin-coated meshes and their adhesion, viability, phenotype, gene expression, and immunomodulatory capacity were fully evaluated. This coating guaranteed MenSC viability, adhesion and did not trigger any change in their stemness and inflammatory profile. Additionally, MenSCs seeded on fibrin-coated meshes significantly decreased CD4+ and CD8+ T cell proliferation, compared to in vitro stimulated lymphocytes (p < 0.0001). Hence, the proposed fibrin coating for PP surgical meshes may allow the local administration of stromal cells and the reduction of the exacerbated inflammatory response following mesh implantation surgery. Reproducible and easy to adapt to other cell types, this method undoubtedly requires a multidisciplinary and translational approach to be improved for future clinical uses.

Cork is the bark of the tree Quercus suber L. which ï¬ nds use in diverse applications. However, a signiï¬ cant percentage is still rejected and burned for energy production, despite containing valuable molecules for materials processing and with important biological activities. Herein, the optimization of the extraction process to obtain these molecules, using mild solvents and conditions, is described within a bioreï¬ nery perspective. The extracts were obtained by direct contact solvent extractions with water, ethanol and its mixtures for different time and temperatures, and evaluated for chemical composition, total phenolic content (TPC) and antioxidant properties [by DPPH radical scavenging, ferric reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC) and oxygen radical absorbance capacity (ORAC) assays]. The results showed that the extraction process is accelerated and higher yields are achieved with the increase in temperature without chemical degradation or compromising the antioxidant capacity. For all solvents, at reï¬ ux temperature, more than 90% of the extractable material is obtained within 6 h (80% within 1 h). The highest TPC and antioxidant capacity are observed for the extracts obtained with mixtures of water and ethanol of similar volumes. The antioxidant capacity measured by DPPH, FRAP and TEAC assays was found to be proportional to the extract TPC, while ORAC is favored for higher percentages of ethanol on the extracting solvent. The main constituents of these extracts are the ellagitannins, vescalagin, castalagin and b-O-ethylvescalagin, along with other phenolic acids (mainly ellagic and gallic acids) and various ï¬ avonols. The extracts stability was monitored up to 1 year of storage with neither reduction in the antioxidant capacity nor chemical degradation. These results show that extracts with strong antioxidant potential and high content of bioactive molecules can be obtained from the processing of waste streams. Cork is a sustainable forest product and the development of new ï¬ elds of application contributes toward a zero waste cycle for a complete material bioreï¬ nery.

Diabetic foot infection (DFI) is an important cause of morbidity and mortality. Antibiotics are fundamental for treating DFI, although bacterial biofilm formation and associated pathophysiology can reduce their effectiveness. Additionally, antibiotics are often associated with adverse reactions. Hence, improved antibiotic therapies are required for safer and effective DFI management. On this regard, drug delivery systems (DDSs) constitute a promising strategy. We propose a gellan gum (GG)‐based spongy‐like hydrogel as a topical and controlled DDS of vancomycin and clindamycin, for an improved dual antibiotic therapy against methicillin‐resistant Staphylococcus aureus (MRSA) in DFI. The developed DDS presents suitable features for topical application, while promoting the controlled release of both antibiotics, resulting in a significant reduction of in vitro antibiotic‐associated cytotoxicity without compromising antibacterial activity. The therapeutic potential of this DDS was further corroborated in vivo, in a diabetic mouse model of MRSA‐infected wounds. A single DDS administration allowed a significant bacterial burden reduction in a short period of time, without exacerbating host inflammatory response. Taken together, these results suggest that the proposed DDS represents a promising strategy for the topical treatment of DFI, potentially overcoming limitations associated with systemic antibiotic administration and minimizing the frequency of administration.

Bacterial colonization of polyurethane (PU) ureteral stents usually leads to severe and challenging clinical complications. As such, there is an increasing demand for an effective response to this unmet medical challenge. In this study, we offer a strategy based on the functionalization of PU stents with chitosan-fatty acid (CS-FA) derivatives to prevent bacterial colonization. Three different fatty acids (FAs), namely stearic acid (SA), oleic acid (OA), and linoleic acid (LinA), were successfully grafted onto chitosan (CS) polymeric chains. Afterwards, CS-FA derivatives-based solutions were coated on the surface of PU stents. The biological performance of the modified PU stents was evaluated against the L929 cell line, confirming negligible cytotoxicity of the developed coating formulations. The antibacterial potential of coated PU stents was also evaluated against several microorganisms. The obtained data indicate that the base material already presents an adequate performance against Staphylococcus aureus, which slightly improved with the coating. However, the performance of the PU stents against Gram-negative bacteria was markedly increased with the surface functionalization approach herein used. As a result, this study reveals the potential use of CS-FA derivatives for surface functionalization of ureteral PU stents and allows for conjecture on its successful application in other biomedical devices.

Deep eutectic solvents (DES) can be formed by bioactive compounds or pharmaceutical ingredients. A therapeutic DES (THEDES) based on ibuprofen, a non-steroidal anti-inflammatory drug, and menthol was synthesized. A controlled drug delivery system was developed by impregnating a starch:poly-ε-caprolactone polymeric blend (SPCL 30:70) with the menthol:ibuprofen THEDES in different ratios (10 and 20 wt %), by supercritical fluid sintering at 20 MPa and 50 oC. The morphological characterization of SPCL matrices impregnated with THEDES was performed by scanning electron microscopy (SEM) and micro-computed tomography (micro-CT) and drug release studies were carried out at 37ºC, in phosphate buffered saline (PBS). The results obtained have shown that the solubility profiles of ibuprofen in PBS are similar in powder form and in THEDES. Nonetheless, when incorporated in a polymeric matrix, ibuprofen in the THEDES form has a faster release profile. The drug release in this system is mostly governed by diffusion, as expected due to the hydrophobic nature of the polymer used as carrier. The outcomes of this work demonstrate the improved performance of THEDES based pharmaceutical formulations and the feasibility to couple with green production technologies to develop enhanced biomaterials for therapeutic applications.

In recent years, deep eutectic solvents (DES) have emerged as a sustainable alternative to ionic liquids mainly due to their lower production costs and higher biodegradability/ biocompatibility(1). DES are defined as a mixture of organic compounds with a melting point significantly lower than that of either individual component(2). When based in natural compounds such as aminoacids, organic acids, sugars or choline derivatives, DES are so called natural deep eutectic solvents (NADES) which fully comply with green technology principles(3). NADES constituted by bioactive substances or active pharmaceutical ingredients (APIs), which we define as therapeutic deep eutectic solvents (THEDES), are a promising source for several pharmaceutical and biomedical applications due to their increased ability to dissolve model drugs by increasing their solubility, permeation and absorption. In this work, we synthetized several THEDES based in choline chloride (ChCl) or menthol conjugated with three different APIs: acetylsalicylic acid (AA), benzoic acid (BA) and phenylacetic acid (PA) with different molar ratios (ChCl:AA 1:1, ChCl:PA 1:1, Menthol:AA 3:1, Menthol:BA 3:1, Menthol:PA 2:1, Menthol:PA 3:1). All THEDES produced were characterized by differential scanning calorimetry and polarized optical microscopy. Dissolution studies performed in PBS for 24 hours shown that THEDES increased significantly the dissolution of all APIs studied compared to the control (APIs only). This increased solubility was even more noticeable for the cases of THEDES with menthol in their composition. In overall, our results suggest the great promise of using THEDES as solubility enhancers in the development of novel and more effective drug delivery systems.

Alexandre Barros is grateful for financial support of FCT through grant EXP/QEQ-EPS/0745/2012, project SWIMS. The research leading to these results has received funding from EU FP7 under grant agreement n°KBBE-2010-266033 (project SPECIAL).

Summary In 27 centres across Europe, the prevalence of deforming spinal Scheuermann’s disease in age-stratified population-based samples of over 10,000 men and women aged 50+ averaged 8 % in each sex, but was highly variable between centres. Low DXA BMD was un-associated with Scheuermann’s, helping the differential diagnosis from osteoporosis. Introduction This study aims to assess the prevalence of Scheuermann’s disease of the spine across Europe in men and women over 50 years of age, to quantitate its association with bone mineral density (BMD) and to assess its role as a confounder for the radiographic diagnosis of osteoporotic fracture. Methods In 27 centres participating in the population-based European Vertebral Osteoporosis Study (EVOS), standardised lateral radiographs of the lumbar and of the thoracic spine from T4 to L4 were assessed in all those of adequate quality. The presence of Scheuermann’s disease, a confounder for prevalent fracture in later life, was defined by the presence of at least one Schmorl’s node or irregular endplate together with kyphosis (sagittal Cobb angle >40° between T4 and T12) or a wedged-shaped vertebral body. Alternatively, the (rare) Edgren-Vaino sign was taken as diagnostic. The 6-point-per-vertebral-body (13 vertebrae) method was used to assess osteoporotic vertebral shape and fracture caseness. DXA BMD of the L2–L4 and femoral neck regions was measured in subsets. We also assessed the presence of Scheuermann’s by alternative published algorithms when these used the radiographic signs we assessed. Results Vertebral radiographic images from 4486 men and 5655 women passed all quality checks. Prevalence of Scheuermann’s varied considerably between centres, and based on random effect modelling, the overall European prevalence using our method was 8 % with no significant difference between sexes. The highest prevalences were seen in Germany, Sweden, the UK and France and low prevalences were seen in Hungary, Poland and Slovakia. Centre-level prevalences in men and women were highly correlated. Scheuermann’s was not associated with BMD of the spine or hip. Conclusions Since most of the variation in population impact of Scheuermann’s was unaccounted for by the radiological and anthropometric data, the search for new genetic and environmental determinants of this disease is encouraged.