3D Bioprinting of Biomimetic Alginate/Gelatin/Chondroitin Sulfate Hydrogel Nanocomposites for Intrinsically Chondrogenic Differentiation of Human Mesenchymal Stem Cells.

3D-printed hydrogel scaffolds biomimicking the extracellular matrix (ECM) are key in cartilage tissue engineering as they can enhance the chondrogenic differentiation of mesenchymal stem cells (MSCs) through the presence of active nanoparticles such as graphene oxide (GO). Here, biomimetic hydrogels were developed by cross-linking alginate, gelatin, and chondroitin sulfate biopolymers in the presence of GO as a bioactive filler, with excellent processability for developing bioactive 3D printed scaffolds and for the bioprinting process. A novel bioink based on our hydrogel with embedded human MSCs presented a cell survival rate near 100% after the 3D bioprinting process. The effects of processing and filler concentration on cell differentiation were further quantitatively evaluated. The nanocomposited hydrogels render high MSC proliferation and viability, exhibiting intrinsic chondroinductive capacity without any exogenous factor when used to print scaffolds or bioprint constructs. The bioactivity depended on the GO concentration, with the best performance at 0.1 mg mL-1. These results were explained by the rational combination of the three biopolymers, with GO nanoparticles having carboxylate and sulfate groups in their structures, therefore, biomimicking the highly negatively charged ECM of cartilage. The bioactivity of this biomaterial and its good processability for 3D printing scaffolds and 3D bioprinting techniques open up a new approach to developing novel biomimetic materials for cartilage repair.

Fabrication and assessment of bifunctional electrospun poly(l-lactic acid) scaffolds with bioglass and zinc oxide nanoparticles for bone tissue engineering.

Electrospun scaffolds based on poly(l-lactic acid) (PLLA) with bioglass (n-BG) and zinc oxide (n-ZnO), and mixture of both, were developed to design bifunctional biomaterials with enhanced bioactive and biocidal properties. The presence of n-BG increased the fiber diameter of the pure PLA from 1.5 ± 0.3 µm to 3.0 ± 0.8 µm for 20 wt%. ZnO and the mixed nanoparticles did not significantly affect the morphology. The mechanical properties decreased with the presence of nanoparticles. Scaffolds based on PLA/n-BG promoted hydroxyapatite (HA) formation in simulated body fluid (SBF) that was inhibited with the presence of ZnO. Notably, mixed particles produced bioactivity although at longer times. The incorporation of n-ZnO produced a biocidal capacity against S. aureus in the polymeric scaffold, reaching a viability reduction of 60 % after 6 h of exposure. When both types of nanoparticles were combined, the bacterial viability reduction was 30 %. Pure PLA scaffolds and the composites with n-BG showed good ST-2 bone marrow-derived cell line viability, scaffolds with n-BG (pure or mixture) presented lower viability. Results validated the use of both n-BG and n-ZnO fillers for the development of novel bifunctional PLA-based scaffolds with both bioactive and biocidal properties for bone tissue engineering applications.

Effect of Gelatin Coating and GO Incorporation on the Properties and Degradability of Electrospun PCL Scaffolds for Bone Tissue Regeneration.

Polymer-based nanocomposites such as polycaprolactone/graphene oxide (PCL/GO) have emerged as alternatives for bone tissue engineering (BTE) applications. The objective of this research was to investigate the impact of a gelatin (Gt) coating on the degradability and different properties of PCL nanofibrous scaffolds fabricated by an electrospinning technique with 1 and 2 wt% GO. Uniform PCL/GO fibers were obtained with a beadless structure and rough surface. PCL/GO scaffolds exhibited an increase in their crystallization temperature (Tc), attributed to GO, which acted as a nucleation agent. Young's modulus increased by 32 and 63% for the incorporation of 1 and 2 wt% GO, respectively, in comparison with neat PCL. A homogeneous Gt coating was further applied to these fibers, with incorporations as high as 24.7 wt%. The introduction of the Gt coating improved the hydrophilicity and degradability of the scaffolds. Bioactivity analysis revealed that the hydroxyapatite crystals were deposited on the Gt-coated scaffolds, which made them different from their uncoated counterparts. Our results showed the synergic effect of Gt and GO in enhancing the multifunctionality of the PCL, in particular the degradability rate, bioactivity, and cell adhesion and proliferation of hGMSC cells, making it an interesting biomaterial for BTE.

Review: Auxetic Polymer-Based Mechanical Metamaterials for Biomedical Applications.

Over the last three decades but more particularly during the last 5 years, auxetic mechanical metamaterials constructed from precisely architected polymer-based materials have attracted considerable attention due to their fascinating mechanical properties. These materials present a negative Poisson's ratio and therefore unusual mechanical behavior, which has resulted in enhanced static modulus, energy adsorption, and shear resistance, as compared with the bulk properties of polymers. Novel advanced polymer processing and fabrication techniques, and in particular additive manufacturing, allow one to design complex and customizable polymer architectures that are particularly relevant to fabricate auxetic mechanical metamaterials. Although these metamaterials exhibit exotic mechanical properties with potential applications in several engineering fields, biomedical applications seem to be one of the most relevant with a growing number of articles published over recent years. As a result, special focus is needed to understand the potential of these structures and foster theoretical and experimental investigations on the potential benefits of the unusual mechanical properties of these materials on the way to high performance biomedical applications. The present Review provides up to date information on the recent progress of polymer-based auxetic mechanical metamaterials mainly fabricated using additive manufacturing methods with a special focus toward biomedical applications including tissue engineering as well as medical devices including stents and sensors.

Superhydrophobic SLA 3D printed materials modified with nanoparticles biomimicking the hierarchical structure of a rice leaf.

The rice leaf, combining the surface properties of lotus leaves and shark skin, presents outstanding superhydrophobic properties motivating its biomimesis. We created a novel biomimetic rice-leaf superhydrophobic surface by a three-level hierarchical structure, using for a first time stereolithographic (SLA) 3D printed channels (100µm width) with an intrinsic roughness from the printing filaments (10µm), and coated with TiO2 nanoparticles (22 and 100nm). This structure presents a maximum advancing contact angle of 165° characterized by lower both anisotropy and hysteresis contact angles than other 3D printed surfaces, due to the presence of air pockets at the surface/water interface (Cassie-Baxter state). Dynamic water-drop tests show that the biomimetic surface presents self-cleaning, which is reduced under UV-A irradiation. The biomimetic surface further renders an increased floatability to 3D printed objects meaning a drag-reduction due to reduced water/solid contact area. Numerical simulations of a channel with a biomimetic wall confirm that the presence of air is essential to understand our results since it increases the average velocity and decreases the friction factor due to the presence of a wall-slip velocity. Our findings show that SLA 3D printing is an appropriate approach to develop biomimetic superhydrophobic surfaces for future applications in anti-fouling and drag-reduction devices.

Shape fidelity, mechanical and biological performance of 3D printed polycaprolactone-bioactive glass composite scaffolds.

Direct ink writing (DIW) is a promising extrusion-based 3D printing technology, which employs an ink-deposition nozzle to fabricate 3D scaffold structures with customizable ink formulations for tissue engineering applications. However, determining the optimal DIW process parameters such as temperature, pressure, and speed for the specific ink is essential to achieve high reproducibility of the designed geometry and subsequent mechano-biological performance for different applications, particularly for porous scaffolds of finite sizes (total volume > 1000 mm3) and controlled pore size and porosity. The goal of this study was to evaluate the feasibility of fabricating Polycaprolactone (PCL) and bio-active glass (BG) composite-based 3D scaffolds of finite size using DIW. 3D-scaffolds were fabricated either as cylinders (10 mm diameter; 15 mm height) or cubes (5 × 5 × 5 mm3) with height/width aspect ratios of 1.5 and 1, respectively. A rheological characterization of the PCL-BG inks was performed before printing to determine the optimal printing parameters such as pressure and speed for printing at 110 °C. Microstructural properties of the scaffolds were analyzed in terms of overall scaffold porosity, and in situ pore size assessments in each layer (36 pores/layer; 1764 pores per specimen) during their fabrication. Measured porosity of the fabricated specimens-PCL: x¯ =46.94%, SD = 1.61; PCL-10 wt%BG: x¯ = 48.29%, SD = 5.95; and PCL-20 wt% BG: x¯=50.87%, SD = 2.45-matched well with the designed porosity of 50%. Mean pore sizes-PCL [x¯ = 0.37 mm (SD = 0.03)], PCL-10%BG [x¯ = 0.38 mm (SD = 0.07)] and PCL-20% BG [x¯ = 0.37 mm (SD = 0.04)]-were slightly fairly close to the designed pore size of 0.4 mm. Nevertheless there was a small but consistent, statistically significant (p < 0.0001) decrease in pore size from the first printed layer (PCL: 0.39 mm; PCL-10%BG: 0.4 mm; PCL-20%BG: 0.41 mm) to the last. SEM and micro-CT imaging revealed consistent BG particle distribution across the layers and throughout the specimens. Cell adhesion experiments revealed similar cell adhesion of PCL-20 wt% BG to pure PCL, but significantly better cell proliferation - as inferred from metabolic activity - after 7 days, although a decrease after 14 days was noted. Quasi-static compression tests showed a decrease in compressive yield strength and apparent elastic modulus with increasing BG fraction, which could be attributed to a lack of adequate mechanical bonding between the BG particles and the PCL matrix. The results show that the inks were successfully generated, and the scaffolds were fabricated with high resolution and fidelity despite their relatively large size (>1000 mm3). However, further work is required to understand the mechano-biological interaction between the BG particle additives and the PCL matrix to improve the mechanical and biological properties of the printed structures.

Electrospun fibers of poly (lactic acid) containing bioactive glass and magnesium oxide nanoparticles for bone tissue regeneration.

Electrospun fibers of poly (lactic acid) (PLA) containing 10 and 20 wt% of bioactive glass (n-BG) and magnesium oxide (n-MgO) nanoparticles of ca. 27 and 23 nm respectively, were prepared toward to application in bone tissue engineering. The addition of both nanoparticles into the PLA will produce a synergic effect increasing its bioactivity and antimicrobial behavior. Neat PLA scaffold and the composites with MgO showed an average fiber diameter of 1.7 ± 0.6 µm, PLA/n-BG and PLA/n-BG/n-MgO fibers presented a significant diameter increase reaching values of ca. 3.1 ± 0.8 µm. Young's modulus of the electrospun scaffolds was affected by the direct presence of the particle and scaffold morphologies. All the composites having n-BG presented bioactivity through the precipitation of hydroxyapatite structures on the surface. Although n-MgO did not add bioactivity to the PLA fibers, they were able to render antimicrobial characteristics reducing the S. aureus viability around 30%, although an effect on E. coli strain was not observed. PLA/n-BG nanocomposites did not display any significant antimicrobial behavior. The different composites increased the alkaline phosphatase (ALP) expression as compared with pure PLA barely affecting the cell viability, meaning a good osteoblastic phenotype expression capacity, with PLA/n-BG presenting the highest osteoblastic expression.

Cytocompatible drug delivery hydrogels based on carboxymethylagarose/chitosan pH-responsive polyelectrolyte complexes.

Several drugs are chemically unstable in the gastric environment and have low bioavailability restricted by intestinal absorption, which motivates the development of alternative routes for drug release, such as transdermal drug carriers for drug delivery to specific areas of the skin. Herein, novel polyelectrolyte complexes (PEC) consisting of carboxymethylagarose (CMA) and chitosan (CS) were prepared. pH-responsive CMA/CS hydrogels were obtained by mixing CMA and CS at various weight ratios. Swelling ratio was modulated by varying the CMA and CS weight ratio, and the highest swelling values were achieved for 2:1 wt% hydrogels at 25 °C and pH 6.0. PEC films were characterized by ATR-FTIR spectroscopy, TGA, DSC, and SEM. Results indicated that CMA and CS were successfully crosslinked by ionic complexation. As a model drug, diclofenac sodium (DS) was loaded in CMA/CS PECs. Association efficiency and loading capacity were ca. 69% and 79%, respectively, exhibiting 67% cumulative release after 72 h at 37 °C and pH 6.0 through Fickian diffusion mechanism. Viability assay of immortalized human keratinocyte (HaCat) cells showed ca. 100% survival in the presence of hydrogels and DS. Therefore, this work suggests that CMA/CS PECs can be applied as pH-responsive carriers for dermal drug delivery.

Effect of Cu- and Zn-Doped Bioactive Glasses on the In Vitro Bioactivity, Mechanical and Degradation Behavior of Biodegradable PDLLA Scaffolds.

Biodegradable polymer scaffolds filled with bioactive glass particles doped with therapeutic metal ions are a novel and promising strategy to repair critical-sized bone defects. In this study, scaffolds based on a poly (D, L-lactide acid) (PDLLA) matrix filled with un-doped and Cu-, Zn- and CuZn-doped bioactive glass particles were produced by freeze-drying and a salt-leaching method. The effects of the doping and content of the glass particles (10 and 30 wt.%) on the morphology, compression properties, apatite formation, and degradation behavior of the scaffolds were evaluated. The scaffolds presented high porosity (~93%) with pores ranged from 100 to 400 µm interconnected by smaller pores and this porosity was kept after the glass particles incorporation. The glass particles reinforced the polymer scaffolds with improvements as high as 130% in elastic moduli, and further promoted the apatite formation on the scaffold surface, both properties depending on the amount and type of filler. The bioactive glass particles boosted the scaffold degradation with the PDLLA/un-doped glass scaffold showing the highest rate, but still retaining structural and dimensional integrity. Our findings show that the incorporation of un-doped and metal-doped bioactive glasses increases the mechanical strength, promotes the bioactivity and modifies the degradation profile of the resulting polymer/glass scaffolds, making them better candidates for bone repair.

Effect of bioglass nanoparticles on the properties and bioactivity of poly(lactic acid) films.

Bioglass nanoparticles (n-BGs, 54SiO2 :40CaO:6P2 O5 mol %) with about 27 nm diameter were synthesized by the sol-gel method and incorporated into a poly(lactic acid) (PLA) matrix by the melting process in order to obtain nanocomposites with filler contents of 5, 10, and 25 wt %. Our results showed that during the cooling scan, the crystallization temperature (Tc ) of the PLA/n-BG nanocomposites decreased 13°C as compared to neat PLA. The presence of nanoparticles also decreased the thermal stability of the PLA matrix, as nanocomposites presented up to about 20°C lower degradation temperatures in a nitrogen atmosphere. The presence of n-BG increased the stiffness of the polymer matrix, and for instance the composite with 25 wt % of filler presented about 52.6% higher Young's modulus than neat PLA. n-BG incorporation into PLA increased also the hydrolytic degradation of the polymer over time. When the PLA composites were immersed in simulated body fluid, an apatite layer was formed on their surface, as verified by Fourier transform infrared, X-Ray Diffraction (XRD), and scanning electron microscopy-EDS, showing that the presence of n-BG induced bioactivity on the PLA matrix. Moreover, the viability of cervical uterine adenocarcinoma cells was higher on PLA/n-BG nanocomposite with 25 wt % of filler. The presence of n-BG barely gave an antibacterial effect on the polymer matrix, despite the well-known biocidal properties of these nanoparticles. Our results show that the presence of n-BGs is a proper route for improving the bioactivity of PLA with potential application in tissue engineering.

Electroactive 3D Printed Scaffolds Based on Percolated Composites of Polycaprolactone With Thermally Reduced Graphene Oxide for Antibacterial and Tissue Engineering Applications.

Applying electrical stimulation (ES) could affect different cellular mechanisms, thereby producing a bactericidal effect and an increase in human cell viability. Despite its relevance, this bioelectric effect has been barely reported in percolated conductive biopolymers. In this context, electroactive polycaprolactone (PCL) scaffolds with conductive Thermally Reduced Graphene Oxide (TrGO) nanoparticles were obtained by a 3D printing method. Under direct current (DC) along the percolated scaffolds, a strong antibacterial effect was observed, which completely eradicated S. aureus on the surface of scaffolds. Notably, the same ES regime also produced a four-fold increase in the viability of human mesenchymal stem cells attached to the 3D conductive PCL/TrGO scaffold compared with the pure PCL scaffold. These results have widened the design of novel electroactive composite polymers that could both eliminate the bacteria adhered to the scaffold and increase human cell viability, which have great potential in tissue engineering applications.

Chondroinductive Alginate-Based Hydrogels Having Graphene Oxide for 3D Printed Scaffold Fabrication.

Scaffolds based on bioconjugated hydrogels are attractive for tissue engineering because they can partly mimic human tissue characteristics. For example, they can further increase their bioactivity with cells. However, most of the hydrogels present problems related to their processability, consequently limiting their use in 3D printing to produce tailor-made scaffolds. The goal of this work is to develop bioconjugated hydrogel nanocomposite inks for 3D printed scaffold fabrication through a micro-extrusion process having improved both biocompatibility and processability. The hydrogel is based on a photocrosslinkable alginate bioconjugated with both gelatin and chondroitin sulfate in order to mimic the cartilage extracellular matrix, while the nanofiller is based on graphene oxide to enhance the printability and cell proliferation. Our results show that the incorporation of graphene oxide into the hydrogel inks considerably improved the shape fidelity and resolution of 3D printed scaffolds because of a faster viscosity recovery post extrusion of the ink. Moreover, the nanocomposite inks produce anisotropic threads after the 3D printing process because of the templating of the graphene oxide liquid crystal. The in vitro proliferation assay of human adipose tissue-derived mesenchymal stem cells (hADMSCs) shows that bioconjugated scaffolds present higher cell proliferation than pure alginate, with the nanocomposites presenting the highest values at long times. Live/Dead assay otherwise displays full viability of hADMSCs adhered on the different scaffolds at day 7. Notably, the scaffolds produced with nanocomposite hydrogel inks were able to guide the cell proliferation following the direction of the 3D printed threads. In addition, the bioconjugated alginate hydrogel matrix induced chondrogenic differentiation without exogenous pro-chondrogenesis factors as concluded from immunostaining after 28 days of culture. This high cytocompatibility and chondroinductive effect toward hADMSCs, together with the improved printability and anisotropic structures, makes these nanocomposite hydrogel inks a promising candidate for cartilage tissue engineering based on 3D printing.

Electroactive Smart Polymers for Biomedical Applications.

The flexibility in polymer properties has allowed the development of a broad range of materials with electroactivity, such as intrinsically conductive conjugated polymers, percolated conductive composites, and ionic conductive hydrogels. These smart electroactive polymers can be designed to respond rationally under an electric stimulus, triggering outstanding properties suitable for biomedical applications. This review presents a general overview of the potential applications of these electroactive smart polymers in the field of tissue engineering and biomaterials. In particular, details about the ability of these electroactive polymers to: (1) stimulate cells in the context of tissue engineering by providing electrical current; (2) mimic muscles by converting electric energy into mechanical energy through an electromechanical response; (3) deliver drugs by changing their internal configuration under an electrical stimulus; and (4) have antimicrobial behavior due to the conduction of electricity, are discussed.

3D Printing of Antimicrobial Alginate/Bacterial-Cellulose Composite Hydrogels by Incorporating Copper Nanostructures.

Novel antimicrobial 3D-printed alginate/bacterial-cellulose hydrogels with in situ-synthesized copper nanostructures were developed having improved printability. Prior to 3D printing, two methods were tested for the development of the alginate hydrogels: (a) ionic cross-linking with calcium ions followed by ion exchange with copper ions (method A) and (b) ionic cross-linking with copper ions (method B). A solution containing sodium borohydride, used as a reducing agent, was subsequently added to the hydrogels, producing in situ clusters of copper nanoparticles embedded in the alginate hydrogel matrix. The method used and concentrations of copper and the reducing agent were found to affect the stability of the alginate/copper hydrogels, with method A producing more stable materials. By increasing the alginate concentration from 1 to 4 wt % and by using method A, alginate/bacterial-cellulose/copper hydrogel structures were 3D-printed having excellent printability as compared with pure alginate hydrogels. It is noteworthy that after reduction with sodium borohydride, the 3D structures presented antimicrobial behavior against Escherichia coli and Staphylococcus aureus strains. Our results introduce a simple route for the production of alginate/cellulose inks with improved behavior toward antimicrobial 3D-printed materials.

In situ antimicrobial behavior of materials with copper-based additives in a hospital environment.

Copper and its alloys are effective antimicrobial surface materials in the laboratory and in clinical trials. Copper has been used in the healthcare setting to reduce environmental contamination, and thus prevent healthcare-associated infections, complementing traditional protocols. The addition of copper nanoparticles to polymer/plastic matrices can also produce antimicrobial materials, as confirmed under laboratory conditions. However, there is a lack of studies validating the antimicrobial effects of these nanocomposite materials in clinical trials. To satisfy this issue, plastic waiting room chairs with embedded metal copper nanoparticles, and metal hospital IV pools coated with an organic paint with nanostructured zeolite/copper particles were produced and tested in a hospital environment. These prototypes were sampled once weekly for 10 weeks and the viable microorganisms were analysed and compared with the copper-free materials. In the waiting rooms, chairs with copper reduced by around 73% the total viable microorganisms present, showing activity regardless of the microorganism tested. Although there were only low levels of microorganisms in the IV pools installed in operating rooms because of rigorous hygiene protocols, samples with copper presented lower total viable microorganisms than unfilled materials. Some results did not have statistical significance because of the low load of microorganisms; however, during at least three weeks the IV pools with copper had reduced levels of microorganisms by a statistically significant 50%. These findings show for the first time the feasibility of utilizing the antimicrobial property of copper by adding nanosized fillers to other materials in a hospital environment.

Encapsulation of specific Salmonella Enteritidis phage f3αSE on alginate-spheres as a method for protection and dosification

Background: Bacteriophages have been proposed as an alternative to control pathogenic bacteria resistant to antibiotics. However, they are not extensively used due to different factors such as vulnerability under environmental conditions and the lack of efficient administration methods. A potential solution is the encapsulation of bacteriophages in hydrogel polymers to increase their viability and as a controlled release method. This work describes the use of alginate-Ca+2 matrixes as mechanisms for protection and dosification of the phage f3αSE which has been successfully used to prevent infections produced by Salmonella Enteritidis. Results: The viability of the pure phage is reduced in near 100% after 1-h incubation at pH 2 or 3. However, the encapsulated phage remains active in 80, 6% at pH 3, while no differences were observed at pH 2, 4 or 7. Exposition of f3αSE to different T° showed that the viability of this phage decreased with increased T° to near 15% at 60°C, while the encapsulated phage remains with 50% viability at same temperature. Finally, the encapsulation of phages showed to extend their presence for 100 h in the medium compared to non-encapsulated phages in a water flow system, which simulate automatic birdbath used in poultry industry, maintaining the phage concentration between 102 and 104 PFU/mL during 250 h. Conclusions: Encapsulation in alginate-Ca+2 spheres can be a good alternative to extend viability of phages and can be used as a phage method dosification method in water flow systems.

Poly(lactic acid) composites based on graphene oxide particles with antibacterial behavior enhanced by electrical stimulus and biocompatibility.

Poly(lactic acid) (PLA) is a biodegradable and biocompatible polyester widely used in biomedical applications. Unfortunately, this biomaterial suffers from some shortcomings related with the absence of both bioactivity and antibacterial capacity. In this work, composites of PLA with either graphene oxide (GO) or thermally reduced graphene oxide (TrGO) were prepared by melt mixing to overcome these limitations. PLA composites with both GO and TrGO inhibited the attachment and proliferation of Escherichia coli and Staphylococcus aureus bacteria depending on the kind and amount of filler. Noteworthy, it is shown that by applying an electrical stimulus to the percolated PLA/TrGO, the antibacterial behavior can be dramatically increased. MTT analysis showed that while all the PLA/GO composites were more cytocompatible to osteoblast-like cells (SaOS-2) than pure PLA, only low content of TrGO was able to increase this property. These tendencies were related with changes in the surface properties of the resulting polymer composites, such as polarity and roughness. In this way, the addition of GO and TrGO into a PLA matrix allows the development of multifunctional composites for potential applications in biomedicine. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1051-1060, 2018.

Effect of CaCO3 Nanoparticles on the Mechanical and Photo-Degradation Properties of LDPE.

CaCO3 nanoparticles of around 60 nm were obtained by a co-precipitation method and used as filler to prepare low-density polyethylene (LDPE) composites by melt blending. The nanoparticles were also organically modified with oleic acid (O-CaCO3) in order to improve their interaction with the LDPE matrix. By adding 3 and 5 wt% of nanofillers, the mechanical properties under tensile conditions of the polymer matrix improved around 29%. The pure LDPE sample and the nanocomposites with 5 wt% CaCO3 were photoaged by ultraviolet (UV) irradiation during 35 days and the carbonyl index (CI), degree of crystallinity (χc), and Young's modulus were measured at different times. After photoaging, the LDPE/CaCO3 nanocomposites increased the percent crystallinity (χc), the CI, and Young's modulus as compared to the pure polymer. Moreover, the viscosity of the photoaged nanocomposite was lower than that of photoaged pure LDPE, while scanning electron microscopy (SEM) analysis showed that after photoaging the nanocomposites presented cavities around the nanoparticles. These difference showed that the presence of CaCO3 nanoparticles accelerate the photo-degradation of the polymer matrix. Our results show that the addition of CaCO3 nanoparticles into an LDPE polymer matrix allows future developments of more sustainable polyethylene materials that could be applied as films in agriculture. These LDPE-CaCO3 nanocomposites open the opportunity to improve the low degradation of the LDPE without sacrificing the polymer's behavior, allowing future development of novel eco-friendly polymers.

PDLLA scaffolds with Cu- and Zn-doped bioactive glasses having multifunctional properties for bone regeneration.

Novel multifunctional scaffolds for bone regeneration can be developed by incorporation of bioactive glasses (BG) doped with therapeutic and antibacterial metal ions, such as copper (Cu) and zinc (Zn), into a biodegradable polymer. In this context, porous composite materials of biodegradable poly(d, l-lactide) (PDLLA) mixed with sol-gel BG of chemical composition 60SiO2 ; 25CaO; 11Na2 O; and 4P2 O5 (mol %) doped with either 1 mol % of CuO or ZnO, and with both metals, were prepared. The cytocompatibility of the scaffolds on bone marrow stromal cells (ST-2) depended on both, the amount of glass filler and the concentration of metal ion, as evaluated by lactate dehydrogenase (LDH) activity, cell viability (water-soluble tetrazolium salt [WST-8]), and by cell morphology (scanning electron microscopy [SEM]) tests. In particular, scaffolds having a filler content of 10 wt % showed the highest cytocompatibility. In addition, compared to the neat polymer, the scaffolds containing Cu promoted the angiogenesis marker (Vascular endothelial growth factor concentration) to a larger extent while scaffolds containing Zn increased the osteogenesis marker (specific alkaline phosphatase-activity). Noteworthy, the scaffolds with both metal ions showed a combined effect on both properties. Cu- and Zn-doped glasses also provided higher antibacterial capacity to PDLLA-based scaffolds against methicillin-resistant S. aureus bacteria than undoped glass. In combination, our results showed that by a proper addition of Cu- and Zn-doped BG to a PDLLA matrix, multifunctional composite scaffolds with enhanced biological activity can be designed for bone tissue regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 746-756, 2017.

Comportamiento antibacteriano de partículas de cobre frente a microorganismos obtenidos de úlceras crónicas infectadas y su relación con la resistencia a antimicrobianos de uso común / Antibacterial activity of copper salts against microorganisms isolated from chronic infected wounds

Background: The antimicrobial activity of copper (Cu+2) is recognized and used as an antimicrobial agent. Aim: To evaluate the antimicrobial activity of copper against microorganisms obtained from chronic cutaneous wound infections. Material and Methods: Five chemical products that contained copper particles in their composition were tested (zeolite, silica, acetate, nitrate and nanoparticle of copper). The antimicrobial activity against antibiotic resistant strains usually isolated from chronic cutaneous wound infections was determined for two of the products with better performance in copper release. Results: The minimal inhibitory and minimal bactericidal concentrations of copper acetate and nitrate were similar, fluctuating between 400-2,000 µg/ml. Conclusions: The studied copper salts show great potential to be used to control both gram positive and gram negative, antibiotic resistant bacteria isolated from wound infections.