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The development of a biocomposite polymeric system for the antibacterial coating of polypropylene mesh materials for hernia repair is reported. Coatings were constituted by a film of chitosan containing randomly dispersed poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles loaded with chlorhexidine or rifampicin. The chlorhexidine-loaded system exhibited a burst release during the first day reaching the release of the loaded drug in three or four days, whereas rifampicin was gradually released for at least 11 days. Both antibacterial coated meshes were highly active against Staphylococcus aureus and Staphylococcus epidermidis (106 CFU/mL), displaying zones of inhibition that lasted for 7 days (chlorhexidine) or 14 days (rifampicin). Apparently, both systems inhibited bacterial growth in the surrounding environment, as well as avoided bacterial adhesion to the mesh surface. These polymeric coatings loaded with biodegradable nanoparticles containing antimicrobials effectively precluded bacterial colonization of the biomaterial. Both biocomposites showed adequate performance and thus could have potential application in the design of antimicrobial coatings for the prophylactic coating of polypropylene materials for hernia repair., The study was supported by Grants SAF2017-89481-P and MAT2017-84277-R from the Spanish Ministry of Science, Innovation and Universities. Financial support from the CIBER-BBN is acknowledged. The study was supported by Grants SAF2017-89481-P and MAT2017-84277-R from the Spanish Ministry of Science, Innovation and Universities. Financial support from the CIBER-BBN is acknowledged (CIBER-BBN Internal Collaborations 2018-2021: “Functionalization of polymer coatings using antimicrobial agents for prevention of mesh infection following hernia surgery” and “Polymeric nanoparticles for the treatment of bacterial diseases”).

Background As an alternative to sutures, meshes used for hernia repair can be fixed using cyanoacrylate-based adhesives. Attempts to improve these adhesives include alkyl-chain lengthening to reduce their toxicity. This preclinical study compares the long-term behavior of cyanoacrylates of different chain lengths already used in hernia repair and new ones for this application. Materials and methods Partial abdominal wall defects were repaired using a Surgipro mesh in 18 New Zealand White rabbits, and groups were established according to the mesh fixation method: sutures (control), Glubran 2 (n-butyl), Ifabond (n-hexyl), and the new adhesives SafetySeal (n-butyl), and Evobond (n-octyl). Six months after surgery, recovered implants were examined to assess adhesive degradation, host tissue reaction, and biomechanical strength. Results All the cyanoacrylate groups showed good host tissue incorporation in the meshes. Macrophage responses to Glubran and Ifabond were quantitatively greater compared with sutures. Cell damage caused by the adhesives was similar, and only Glubran induced significantly more damage than sutures. Significantly lower collagen 1/3 messenger RNA expression was induced by Ifabond than the remaining fixation materials. No differences were observed in collagen expression except slightly reduced collagen I deposition in Glubran/Ifabond and collagen III deposition in the suture group. Mechanical strengths failed to vary between the suture and cyanoacrylate groups. Conclusions All cyanoacrylates showed good long-term behavior and tolerance irrespective of their long or intermediate chain length. Cyanoacrylate residues persisted at 6 mo, indicating their incomplete degradation. Biomechanical strengths were similar both for the adhesives and sutures.

The photophysical properties of naphthalimide-based fluorophores can be easily tuned by chemical manipulation of the substituents on that privileged scaffold. Replacement of a OMe group at position 6 in 2-(hydroxyl)ethyl-naphthalimide derivatives by diverse amines, including 2-(hydroxyl)ethylamine, trans-(4-acetamido)cyclohexylamine and azetidine increases the solvatochromic (ICT) character, while this replacement in 2-(dimethylamino)ethyl-naphthalimide analogues (PET fluorophores) decrease their solvent polarity sensitivity or even reversed them to solvatochromic fluorophores. These fluorophores resulted macrophage nucleus imaging probes, which bind DNA as intercalants and showed low cytotoxicity in human cancer cells, The work was supported by grants SAF2012-32209, FU2015-67284-R, CTQ2017-85658-R form the Spanish Ministerio de Economía y Competividad, Agencia Estatal de Investigación and the European Regional Development Fund; and the CSIC grant 201580E073

Semi-interpenetrating polymer networks (semi-IPNs) have attracted much attention in recent years as biomaterials with a high potential in tissue engineering and controlled drug release. In this article, semi-IPNs were synthetized by free radical polymerization of 2-hydroxyethyl methacrylate (HEMA) in the presence of poly( l -lactic acid) (PLLA) with contents of 5, 10 and 20 wt.% at high temperature (150 °C). The study focused on the analysis of thermal and mechanical properties, wettability, swelling kinetics in buffered solutions of different pH, and biocompatibility using fibroblasts of human embryonic skin. Segregation of the components in different microdomains was verified by morphological analysis through scanning electron microscopy (SEM). Differential scanning calorimetry (DSC) results revealed that the poly(2-hydroxyethyl methacrylate) (PHEMA) network is amorphous and the PLLA is semi-crystalline. Mechanical analysis provided Young’s modulus values in the range 240–370 MPa in tensile tests, and storage modulus (E′) values at 37 °C, 1 Hz, in the range 800–1200 MPa. Equilibrium water uptake measurements displayed material dependence on composition and pH. Swelling kinetics presented good agreement with a second-order diffusion process in all media. No sample present cytotoxicity and the cell migration process occupied many semi-IPNs pores closing them and indicating good cellular recognition. In overall, these networks can be considered for their application as scaffolds for bone defects augmentation and subchondral cartilage repair.

The article deals with a comparative analysis of the parameters of the polymerization in physiological conditions of three commercially available alkyl cyanoacrylates, n-butyl cyanoacrylate (GLUBRAN 2), n-hexyl cyanoacrylate (IFABOND), and n-octyl cyanoacrylate (EVOBOND), the cell behavior of the corresponding polymers and the application of these adhesives in the fixation of surgical polypropylene meshes for hernia repair in an animal model of rabbits. The results obtained demonstrate that the curing process depends on the nature of the alkyl residue of the ester group of cyanoacrylate molecules, being the heat of polymerization lower for the octyl derivative in comparison with the hexyl and butyl, and reaching a maximum temperature of 35 °C after a time of mixing with physiological fluids of 60-70 s. The cell behavior demonstrates that the three systems do not present toxicity for fibroblasts and low adhesion of cells, which is a positive result for application as tissue adhesives, especially for the fixation of abdominal polypropylene meshes for hernia repair. The animal experimentation indicates the excellent tolerance of the meshes fixed with the cyanoacrylic adhesives, during at least a period of 90 d, and guarantees a good adhesion for the application of hernia repair meshes.

Osteochondral (OC) regeneration faces several limitations in orthopedic surgery, owing to the complexity of the OC tissue that simultaneously entails the restoration of articular cartilage and subchondral bone diseases. In this study, novel biofunctional hierarchical scaffolds composed of a horseradish peroxidase (HRP)-cross-linked silk fibroin (SF) cartilage-like layer (HRP-SF layer) fully integrated into a HRP-SF/ZnSr-doped β-tricalcium phosphate (β-TCP) subchondral bone-like layer (HRP-SF/dTCP layer) were proposed as a promising strategy for OC tissue regeneration. For comparative purposes, a similar bilayered structure produced with no ion incorporation (HRP-SF/TCP layer) was used. A homogeneous porosity distribution was achieved throughout the scaffolds, as shown by micro-computed tomography analysis. The ion-doped bilayered scaffolds presented a wet compressive modulus (226.56 ± 60.34 kPa) and dynamic mechanical properties (ranging from 403.56 ± 111.62 to 593.56 ± 206.90 kPa) superior to that of the control bilayered scaffolds (189.18 ± 90.80 kPa and ranging from 262.72 ± 59.92 to 347.68 ± 93.37 kPa, respectively). Apatite crystal formation, after immersion in simulated body fluid (SBF), was observed in the subchondral bone-like layers for the scaffolds incorporating TCP powders. Human osteoblasts (hOBs) and human articular chondrocytes (hACs) were co-cultured onto the bilayered structures and monocultured in the respective cartilage and subchondral bone half of the partitioned scaffolds. Both cell types showed good adhesion and proliferation in the scaffold compartments, as well as adequate integration of the interface regions. Osteoblasts produced a mineralized extracellular matrix (ECM) in the subchondral bone-like layers, and chondrocytes showed GAG deposition. The gene expression profile was different in the distinct zones of the bilayered constructs, and the intermediate regions showed pre-hypertrophic chondrocyte gene expression, especially on the BdTCP constructs. Immunofluorescence analysis supported these observations. This study showed that the proposed bilayered scaffolds allowed a specific stimulation of the chondrogenic and osteogenic cells in the co-culture system together with the formation of an osteochondral-like tissue interface. Hence, the structural adaptability, suitable mechanical properties, and biological performance of the hierarchical scaffolds make these constructs a desired strategy for OC defect regeneration., This study was funded by the Portuguese Foundation for Science and Technology (FCT) for the HierarchiTech project (M-ERA-NET/0001/2014). The project FROnTHERA (NORTE-01-0145-FEDER-000023), was supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). The FCT distinctions attributed to JMO (IF/00423/2012 and IF/01285/ 2015), and ALO (IF/00411/2013). VPR (PD/BD/113806/ 2015) and JBC (PD/BD/113803/2015) were awarded PhD scholarships under the financial support from FCT/MCTES and FSE/POCH, PD/59/2013. I.F.C. was awarded an FCT Ph.D. scholarship (SFRH/BD/99555/2014).

To avoid dental implant-related infections and to promote the osseointegration of titanium implants, the application of silicon and chitosan containing coatings is proposed. Silicon is a well-known osteogenic element and chitosan was selected to confer the antibacterial properties. The synthesis of hybrid silica-chitosan coatings using the sol-gel process is presented and the characterization using Si-NMR to verify the correct formation of the network is discussed. The C NMR spectroscopy was used to confirm the covalent union between chitosan and the silicon network. Hydrolytic degradation and silicon release studies showed the effective silicon release from the hybrids and, hence, the possibility to promote bone formation. The introduction of different amounts of chitosan and tetraethyl orthosilicate (TEOS) modulated the Si release. The analysis of cell cultures in vitro demonstrated that the hybrid coatings were not cytotoxic and promoted cell proliferation on their surfaces. The coatings containing 5%–10% chitosan had substantial antibacterial properties., This research was supported by the Spanish Ministry of Economy and Competitiveness projectMAT2017-86043-R, the University of the Basque Country (UPV/EHU) project UFI11/56, Basque Government project IT611-13 and a personal grant (predoc-2016-1-0141) and Universitat Jaume I (grant numbers Predoc/2014/25, UJI-B2017-37). The authors thank for technical and personnel support provided by SGIker of UPV/EHU and the European funding sources (ERDF and ESF). We are especially grateful to Antonio Coso and the personnel of his company (Ilerimplant S.L) for their cooperation and to María Rosa Ana Ramírez for her service at the ICTP laboratories.

The lack of polarity sensing fluorophores with OFF-ON features when increasing the environment polarity has limited the monitoring of biological processes that involve an increase in local hydrophilicity. In this work, replacement of a hydroxyl group by a dimethylamino group transformed solvatochromic ICT naphthalimide- and quinolimide-based fluorophores into reversed solvatochromic ones, with higher emission in polar than in apolar environments. Excited-state dynamics studies, TD-DFT calculations, X-ray and NMR support the existence of a folded conformation for the 2-(dimethylamino)ethyl chain upon the imide ring in apolar solvents, where the dimethylamino group would quench the fluorescence by a PET effect, while in polar solvents the chain has an extended conformation, where the PET is hindered. These PET fluorophores have given rise to H2O and pH sensors in organic solvents as well as to bright macrophage cytoplasm imaging probes.

Herein, multilayer polysaccharide films were proposed and characterized as biomaterials for the local and controlled release of an antitumoral drug. To that aim, multilayer films of alginate (Alg) and chitosan (Chi) were built up through spray assisted layer-by-layer (LbL) technique employing an automatic equipment. A specific drug against breast cancer, tamoxifen (TMX), was incorporated in different intermediate positions of the multilayer Alg/Chi films. Our findings highlight that Alg/Chi multilayer films can be employed for sustained and local TMX delivery and their therapeutic effect can be modulated and optimized by the number of bilayers deposited over the loaded tamoxifen, the quantity of tamoxifen loaded in several intermediate positions and the total area of the film., The authors would like to thank Rosa Ana Ramirez and Raquel de Roba for their assistance regarding cell culture experiments. Financial support from MINECO (MAT2017-83014-C2-1-P and MAT2017-84277- R) is gratefully acknowledged. Rebeca Hernández thanks MEC for a Ramón y Cajal contract and Miryam Criado thanks MEC for a FPU fellowship.

AIMS This study examines the intraperitoneal behavior of two cyanoacrylate tissue adhesives: Ifabond® and a new, non-marketed octyl cyanoacrylate adhesive (OCA) used for the intraperitoneal fixation of a laminar expanded polytetrafluoroethylene (ePTFE) mesh. MATERIAL AND METHODS In 36 New Zealand White rabbits, 3 × 3 cm (n = 24) or 1.5 × 3 cm (n = 12) fragments of ePTFE mesh (Preclude® , Gore, Flagstaff, USA) were fixed to the parietal peritoneum using OCA or Ifabond® . Peritoneal fluid was obtained at the time of implant and at 2 weeks postimplant for determination of the cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). At 14 or 90 days postsurgery, the animals were euthanized and the meshes excised to assess host tissue incorporation, the macrophage response, apoptosis and fixation strength (T-peel tensiometry). RESULTS Peritoneal fluid IL-6 and TNF-α concentrations were similar in the OCA and Ifabond® groups. Both adhesives gave rise to adequate mesothelialization of the laminar ePTFE. Macrophage counts were similar for the two study groups, but a significantly increase in macrophage response was observed from 14 to 90 days for Ifabond® . At 90 days postimplant, apoptotic cell counts was lower for the implants fixed with OCA and a fixation strength was significantly lower for OCA. CONCLUSIONS Despite similar cytokine levels at 2 weeks and similar host tissue incorporation observed for the meshes fixed with the two adhesives, the use of Ifabond® gave rise to a greater apoptosis rate, although this adhesive provided a stronger fixation bond. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 312-319, 2017.

INTRODUCTION: Lightweight (LW) polypropylene (PP) meshes better adapt to host tissue, causing less fibrosis and inflammatory responses than high-density meshes. Mesh fixation using tissue adhesives (TA) that replace conventional sutures may improve the process of hernia repair and tissue trauma. This preclinical study compares the behavior of different cyanoacrylate-based adhesives in the fixation of LW-PP meshes for hernia repair. METHODS: Partial abdominal wall defects were repaired using LW-PP Optilene meshes in New Zealand rabbits. The following groups were established according to the mesh fixation method: Suture (control), Glubran 2 (n-butyl), Ifabond (n-hexyl), SafetySeal (n-butyl) and Evobond (n-octyl). At 14, 90 and 180 days after surgery, the recovered implants were examined to assess the host tissue integration, the macrophage response and the biomechanical strength. RESULTS: All the groups showed optimal host tissue incorporation regardless of the fixation procedure. Significantly increased levels of collagen 1 and collagen 3 gene expression (p, The study was supported by Grant “SAF2014-55022-P” and “SAF2017-89481-P” from the Spanish Ministry of Economy and Competitiveness.

Excellent adherence properties of blue mussels have been attributed to a catechol-containing amino acid, L-3,4-dihydroxyphenylalanine. This natural form of adhesion has been a source to develop bioadhesive polymers that adhere to biological interfaces. In this study, we describe a bioinspired approach for preparing bioadhesive and biocompatible materials based on synthetic low molecular weight copolymers of a flexible catechol-functionalized methacrylate (CEMA) and N-vinylcaprolactam. Copolymers with CEMA contents in the range 0.9–13.5 mol% were obtained by radical copolymerization. These systems show good biocompatibility and provide good antioxidant behavior and anti-inflammatory activity. Likewise, hydrogels prepared by mixture of a selected copolymer with gelatin possess good bone bioadhesive properties. These findings show that copolymer composition can be used as a tool for the preparation of biomedical systems with tunable properties and great potential for the development of drug delivery systems and bioactive gels that can be applied in tissue regeneration processes., This work was supported by CIBER-BBN (Spain) and the Spanish Ministry of Economy and Competitiveness [project MAT2014-51918- C2-1-R and M. Puertas-Bartolomé scholarship

In craniofacial tissue regeneration, the current gold standard treatment is autologous bone grafting, however, it presents some disadvantages. Although new alternatives have emerged there is still an urgent demand of biodegradable scaffolds to act as extracellular matrix in the regeneration process. A potentially useful element in bone regeneration is strontium. It is known to promote stimulation of osteoblasts while inhibiting osteoclasts resorption, leading to neoformed bone. The present paper reports the preparation and characterization of strontium (Sr) containing hybrid scaffolds formed by a matrix of ionically cross-linked chitosan and microparticles of poly(ε-caprolactone) (PCL). These scaffolds of relatively facile fabrication were seeded with osteoblast-like cells (MG-63) and human bone marrow mesenchymal stem cells (hBMSCs) for application in craniofacial tissue regeneration. Membrane scaffolds were prepared using chitosan:PCL ratios of 1:2 and 1:1 and 5 wt % Sr salts. Characterization was performed addressing physico-chemical properties, swelling behavior, in vitro biological performance and in vivo biocompatibility. Overall, the composition, microstructure and swelling degree (≈245%) of scaffolds combine with the adequate dimensional stability, lack of toxicity, osteogenic activity in MG-63 cells and hBMSCs, along with the in vivo biocompatibility in rats allow considering this system as a promising biomaterial for the treatment of craniofacial tissue regeneration., Authors thank CIBER-BBN, Spain, the Spanish Ministry of Economy and Competitivity (project MAT2017-84277-R) and Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT) UNAM, Mexico, (project IA20947) for supporting this work.

Chondroitin sulfate (CS) is a relevant family of polysaccharides that participates in a large variety of biological events that are related to neural processes by regulating various growth factors through the pattern and degree of sulfation of the polysaccharide. However, their own complexity makes their optimization for biomedical applications a difficult undertaking. Thus, a different perspective has to be taken. Herein, we show that the particular sulfate distribution within the disaccharide repeating-unit plays a key role in the binding of growth factors (GFs). In particular, this disposition modulates the surface charge of the helical structure that, interestingly, has a significant influence on the binding capacity of CSs with several GFs. This fact should be carefully considered in the design of new ligands with improved activity as GFs ligands., The authors gratefully acknowledge the financial support provided by the Spanish Ministerio de Economía y Competitividad (Grant MAT2015-65184-C2-2-R) and by CSIC project iCOOPB20237. The authors thank Prof. Jian Liu (School of Pharmacy, University of North Carolina) for providing a plasmid expression of the chondroitin, lyase ABC, and V. M. Moreno for cloning the 4-O-endo-sulfatase from Bacteroides thetaiotaomicron.

The present study reports a three-step bio-safe process for fabricating porous polylactic acid (PLA) scaffolds with a biomimetic design of the porosity and the architecture and applications in bone tissue engineering (bTE). The process starts with a PLA-ethyl lactate solution and involves the combination of thermal induced phase separation (TIPS) and supercritical CO2 (scCO2) drying techniques for the development of a nano-fibrous architecture. In a third step, it was further combined with a gelatin leaching technique to create an additional interconnected network of large pores of appropriate size and distribution. The effect of the size of the gelatin particles, selected in three different ranges: 100-200, 200-400 and 400-600 μm, on the morphology, porosity and textural features of PLA scaffolds is assessed by means of scanning electron microscopy analysis, gravimetric measurements, image analysis and low-temperature N2 adsorption. Finally, in vitro cell culture tests are carried out by using human osteosarcoma cell line MG63 in order to evaluate the biological response of the different scaffolds prepared and to assess their potential for bTE applications.

Compounds having the general formula MFO·4H2O where M = Ca or Sr and FO = a folate anion were prepared and their structure and physico-chemical properties were determined by elemental and thermal TGA, DSC analysis, FTIR, and EDAX spectroscopies and DRX. The results indicate that the two compounds form stable structures where folic acid acts as a self-bridging ligand via two bidentate carboxylate groups. Moreover the two compounds showed a low toxicity in vitro response as h-osteoblast cell viability was not negatively affected by the presence of folate derivatives within the range of 0.063-0.5 mg ml-1. The results also indicate that the folate derivatives that are formed overcome the toxic effects related to free Sr2+ ions. The range of maximum cell viability corresponding with a concentration of SrFO falls within the in vitro physiologically active range for strontium while within the same range the strontium derivative showed a potential osteogenic activity as indicated by the overexpression of ALP activity.

Stabilized magnetic nanoparticles are the subject of intense research for targeting applications and this work deals with the design, preparation and application of specific core-shell nanoparticles based on ionic crosslinked chitosan. The nanometric size of the materials was demonstrated by dynamic light scattering (DLS) and field emission scanning electron microscopy (FESEM) that also proved an increase of the size of chitosan nanoparticles (NPs) with the magnetite content. Steady oscillatory rheology measurements revealed a gel-like behavior of aqueous dispersions of chitosan NPs with concentrations ranging from 0.5% to 2.0% (w/v). The cytotoxicity of all the materials synthesized was analyzed in human fibroblasts cultures using the Alamar Blue and lactate dehydrogenase (LDH) assays. The measured specific power absorption under alternating magnetic fields (f = 580 kHz, H = 24 kA/m) indicated that magnetic core-shell chitosan NPs can be useful as remotely driven heaters for magnetic hyperthermia. © 2013 Elsevier Ltd.

Nanocomposites were prepared with segmented polyurethanes and Cloisite 30B by either solution mixing or in situ polymerization and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis and X-ray diffraction. Cytotoxicity and genotoxicity were assessed with lymphocytes while cell viability was measured by the methyl tetrazolium assay using fibroblasts. It was found that in situ polymerization rendered exfoliated nanocomposites with higher glass transition temperature, tensile modulus and thermal stability compared to nanocomposites obtained by solution mixing. The mitotic index of lymphocytes was significantly reduced at high clay concentrations (6 wt% and 10 wt%), while fibroblast viability improved in the presence of extract obtained after days 2 and 7.

The less traumatic use of surgical adhesives rather than sutures for mesh fixation in hernia repair has started to gain popularity because they induce less host tissue damage and provoke less postoperative pain. This study examines the host tissue response to a new cyanoacrylate (CA) adhesive (n-octyl, OCA). Partial defects (3 × 5 cm) created in the rabbit anterior abdominal wall were repaired by mesh fixation using OCA, Glubran2(n-butyl-CA), Ifabond(n-hexyl-CA) or sutures. Samples were obtained at 14/90 days for morphology, collagens qRT-PCR/immunofluorescence and biomechanical studies. All meshes were successfully fixed. Seroma was detected mainly in the Glubran group at 14 days. Meshes fixed using all methods showed good host tissue incorporation. No signs of degradation of any of the adhesives were observed. At 14 days, collagen 1 and 3 mRNA expression levels were greater in the suture and OCA groups, and lower in Ifabond, with levels varying significantly in the latter group with respect to the others. By 90 days, expression levels had fallen in all groups, except for collagen 3 mRNA in Ifabond. Collagen I and III protein expression was marked in the suture and OCA groups at 90 days, but lower in Ifabond at both time points. Tensile strengths were similar across groups. Our findings indicate the similar behavior of the adhesives to sutures in terms of good tissue incorporation of the meshes and optimal repair zone strength. The lower seroma rate and similar collagenization to controls induced by OCA suggests its improved behavior over the other two glues. Graphical Abstract: This article deals with a preclinical study to examine different aspects of the repair process in the host of three alkyl cyanoacrylates (n-butyl (GLUBRAN 2), n-hexyl (IFABOND), and n-octyl cyanoacrylate (EVOBOND)) compared to sutures (control), in the fixation of surgical meshes for hernia repair. It goes into detail about collagen deposition in the repair zone at short and medium term. The results obtained demonstrate lower seroma rate and similar collagenization to sutures induced by the n-octyl suggesting better behavior than the other two cyanoacrylates. [InlineMediaObject not available: see fulltext.], The study was supported by Grant SAF2014-55022-P from the Spanish Ministry of Economy and Competitiveness

Novel antimicrobial hydrogels with good mechanical and physical properties were synthesized by autoclaving aqueous mixtures of poly(vinyl alcohol) and poly(methyl vinyl ether-alt-maleic anhydride). The structure of these materials was studied by infrared spectroscopy, scanning electron microscopy and solid state nuclear magnetic resonance. The swelling behavior, mechanical properties and adhesion of the hydrogels to porcine skin were evaluated. It was established that these hydrogels exhibited antimicrobial properties and inhibited bacteria growth against Staphylococcus aureus. The biocompatibility of the hydrogels was confirmed using an MTT assay (indirect cytotoxicity) and by monitoring cell proliferation in contact with the gels (direct cytotoxicity)., The authors acknowledge the University of Reading and ConvaTec Ltd for funding this research project. Chemical Analysis Facility (University of Reading) is acknowledged for access to FTIR, NMR and SEM. Dr Radoslaw M. Kowalczyk is acknowledged for recording solid state NMR spectra and Miss Amanpreet Kaur for her help with SEM. Brett Symonds is thanked for analysis of the molecular weight of PVA samples using GPC and help during the preparation of this manuscript.

Background Synthetic tissue adhesives (TA) are sometimes used in hernia repair surgery. This study compares the use of a new, noncommercial, long-chain cyanoacrylate (n-octyl) TA and Ifabond for mesh fixation. Materials and methods In two implant models in the rabbit, expanded polytetrafluorethylene meshes were fixed to the parietal peritoneum using a TA or tacks (intraperitoneal model), or polypropylene meshes used to repair partial abdominal wall defects were fixed with a TA or sutures (extraperitoneal model). Animals were euthanized 14 or 90 d postsurgery and implant specimens were processed for microscopy (labeling of macrophages and apoptotic cells), peritoneal fluid and biomechanical strength testing. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were determinated in peritoneal fluid. Results Mesothelial cell deposition on the intraperitoneal implants fixed using the new TA and Ifabond was adequate and similar IL-6 and TNF-α levels were detected in these implants. Intraperitoneal meshes fixed with tacks showed IL-6 overexpression. Three months after surgery, macrophage and apoptotic cell rates were higher for the intraperitoneal implants fixed with Ifabond versus the new TA or tacks. In the extraperitoneal model, reduced macrophage and cell damage responses were observed in the meshes fixed with sutures versus both TA. Tensile strengths were greater for the tacks versus TA in the intraperitoneal implants and similar for the sutures and TA in the extraperitoneal implants (90 d). Conclusions Both TA showed a good cell response in both models. Their use in an intraperitoneal location resulted in reduced tensile strength compared with the tacks. However, strengths were comparable when extraperitoneal implants were fixed with these adhesives or sutures.

Drug eluting coronary stents coated with a bioactive and biostable polymer system (THBA70), based on acrylate copolymers bearing a salicylic acid derivative as side substituent, were evaluated. The microstructural architecture of the copolymer THBA70 comprises a random copolymer of a methacrylate derivative from triflusal (4-trifluoromethyl salicylic acid) with 45 mol% of THEMA (2-methacryloyloxyethyl [2-(acetyloxy)-4-(trifluoromethyl)] benzoate), which makes the system anti-thrombogenic with good adhesion to the surface of metallic stents. The bioactive coating prevented thrombosis, an adverse effect associated with the implantation of drug-eluting stents. The in vitro drug delivery of drug-eluting stents under dynamic conditions indicated excellent controlled drug release. The THBA70 films loaded with relatively low concentrations of taxol or simvastatin in contact with fibroblasts produced inhibition of cell proliferation with a dose-dependent bioactivity.

In this study, a novel electrospun hybrid scaffold was developed, which consists of a blend of a modified natural substance, hydroxypropyl starch (HPS) with a synthetic one, poly(ethylene oxide) (PEO). Nanofibers with varying polysaccharide contents were fabricated using water as solvent and the electrospinning process conditions investigated as a function of the weight ratio of the blend. The fibers were characterized through mean diameter and morphology by scanning electron microscopy. Micrographs clearly showed the effect of HPS/PEO weight ratio of the blend on the nanofibers formation. Stability of the fibers was enhanced by coating with hydrophobic poly(methyl methacrylate) (PMMA). In vitro degradation analysis of the coated mats after 1 month of immersion showed porous formation, whereas the fibrous structure was retained. The biological response of the mats against human fibroblasts proved that cells were able to adhere to and proliferate on the fibrous materials. Thus, the feasibility of producing nanofibers of HPS/PEO blends with high proportion of starch and their biocompatibility after coating with PMMA was demonstrated, indicating that these materials have potential to be used as scaffolds in tissue engineering applications., The financial support has been granted by Ministry of Science and Innovation through the project MAT2010-18155 and by the University of the Basque Country (UPV) with ‘‘University of the Basque Country group grants.’’ M. Fernández-Gutiérrrez also thanks to the JAE-doc program of CSIC.

This article reports the fabrication and characterization of NPs based on the self-assembling of polymeric drugs with amphiphilic character synthetized from oleyl 2-acetamido-2-deoxy-α-D-glucopyranoside methacrylate and vinyl pyrrolidone (OAGMA-VP). NPs were spherical, with an apparent hydrodynamic diameter between 91 and 226 nm and with zeta potential values that ensure stability. Atomic concentrations of C, O, and N, determined by X-ray photoelectron spectroscopy (XPS) of NPs, compared well with the corresponding theoretical values. High resolution XPS C1s spectra suggest that the carbons bound to heteroatoms or carbonyl groups are preferentially situated on the surface of the NP samples. ToF-SIMS spectra analyzed by principal component analysis (PCA) indicated that ions coming from acetyl and oleyl groups of OAGMA play important roles in the outer structure of NPs. Water contact angle and surface tension values of NPs were characteristic of hydrophilic surfaces, confirming the location of VP sequences on the surface. Cell culture assays showed that copolymeric NPs did not compromise biocompatibility of human fibroblasts according to ISO standard, but they were cytotoxic on a human glioblastoma cell line (A-172), This work was supported by Ministerio de Economiá y Competitividad, (MAT2010-18155). M.F.-G. also thanks to the JAE-doc program of CSIC. The assistance of Dr. Lara Gamble and Winston Ciridon in the SIMS and XPS assays and the support of NESAC/BIO (NIH EB-002027) is appreciated

The preparation, characterization, and analysis of physicochemical and biological properties of a new bioactive polymer system, based on a copolymer of an acrylic derivative of triflusal (a molecule with chemical structure related to aspirin with antiaggregating activity for platelets) is described and evaluated as thin bioactive coating for vascular grafts and coronary stents. The acrylic monomer derived from triflusal (THEMA) provides random copolymers when it is polymerized with butyl acrylate (BA), according to their reactivity ratios, r(THEMA) = 1.05 and r(BA) = 0.33. The copolymer THBA70, containing a molar composition f(THEMA) = 0.45 and f(BA) = 0.55 presents the optimal properties of stability, flexibility, and adhesion, with a T(g) = 21 ± 2 °C, to be applied as bioactive and biostable coatings for vascular grafts and coronary stents. Thin films of this copolymer system present an excellent biocompatibility and a good inherent antiaggregant activity for platelets.

Partially biodegradable porous scaffolds incorporating bioactive molecules prepared by clean techniques posses an enormous interest in tissue engineering applications. Poly(methyl methacrylate)–poly( l -lactic acid) (PMMA–PLA) blends were submitted to CO2 supercritical conditions (P = 160–260 bar, T = 60 °C) after certain time and then rapidly depressurized to obtain porous structures that have been related with the supercritical parameters and to the polymer blend composition. In some cases ibuprofen was also incorporated to the formulations previously to the CO2 treatment and studied the appropriate conditions for avoiding its extraction in SCCO2. Scaffolds purity, thermal transitions, swelling and degradation behaviour, and the ibuprofen release were also studied to determine the appropriate scaffolds with a desired porosity for cell seeding. Cell culture was performed on the selected porous scaffolds using human fibroblast examined by scanning electron microscopy (SEM).

Polymeric drugs based on random copolymers with antimitotic activity were obtained by free radical copolymerization of oleyl 2-acetamido-2-deoxy-R-D-glucopyranoside methacrylate (OAGMA) and 2-ethyl-(2- pyrrolidone) methacrylate (EPM) at low and high conversion and analyzed in terms of microstructure, physicochemical, and biological properties. Reactivity ratios of monomers were found to be rOAGMA ) 1.34 and rEPM ) 0.98, indicating the obtaining of statistical copolymers with random sequence distribution of the comonomeric units in the macromolecular chains. The glass transition temperature of the copolymers presents a negative deviation from the predicted values according to the Fox equation, suggesting a higher flexibility of the alternating diad. Copolymeric systems with OAGMA contents between 10-50 mol % presented thermosensitive behavior in a heating process showing cloud point temperatures (CPT) in the range 45-28 °C with increasing OAGMA content and hysteresis in one heating-and-cooling cycle. In vitro glycolipid release studies revealed the stability of the ester group in culture medium. The polymeric drugs with 30 and 50 mol % OAGMA presented antimitotic activity on a human glioblastoma line, but they were less toxic on normal human fibroblast cultures., Financial support from the Comisio´n Interministerial de Ciencia y Tecnología, CICYT, (MAT2007- 63355) and NoE EXPERTISSUES (UE Contract No. 500283- 2) is gratefully acknowledged

This study examines the intraperitoneal behavior of two cyanoacrylate tissue adhesives: IfabondIn 36 New Zealand White rabbits, 3 × 3 cm (n = 24) or 1.5 × 3 cm (n = 12) fragments of ePTFE mesh (PrecludePeritoneal fluid IL-6 and TNF-α concentrations were similar in the OCA and IfabondDespite similar cytokine levels at 2 weeks and similar host tissue incorporation observed for the meshes fixed with the two adhesives, the use of Ifabond

¿-Tocopheryl succinate (¿-TOS) is a well-known mitochondrially targeted anticancer compound, however, it is highly hydrophobic and toxic. In order to improve its activity and reduce its toxicity, new surfactant-free biologically active nanoparticles (NP) were synthesized. A methacrylic derivative of ¿-TOS (MTOS) was prepared and incorporated in amphiphilic pseudoblock copolymers when copolymerized with N-vinylpyrrolidone (VP) by free radical polymerization (poly(VP-co-MTOS)). The selected poly(VP-co-MTOS) copolymers formed surfactant-free NP by nanoprecipitation with sizes between 96 and 220 nm and narrow size distribution, and the in vitro biological activity was tested. In order to understand the structure-activity relationship three other methacrylic monomers were synthesized and characterized: MVE did not have the succinate group, SPHY did not have the chromanol ring, and MPHY did not have both the succinate group and the chromanol ring. The corresponding families of copolymers (poly(VP-co-MVE), poly(VP-co-SPHY), and poly(VP-co-MPHY)) were synthesized and characterized, and their biological activity was compared to poly(VP-co-MTOS). Both poly(VP-co-MTOS) and poly(VP-co-MVE) presented triple action: reduced cell viability of cancer cells with little or no harm to normal cells (anticancer), reduced viability of proliferating endothelial cells with little or no harm to quiescent endothelial cells (antiangiogenic), and efficiently encapsulated hydrophobic molecules (nanocarrier). The anticancer and antiangiogenic activity of the synthesized copolymers is demonstrated as the active compound (vitamin E or ¿-tocopheryl succinate) do not need to be cleaved to trigger the biological action targeting ubiquinone binding sites of complex II. Poly(VP-co-SPHY) and poly(VP-co-MPHY) also formed surfactant-free NP that were also endocyted by the assayed cells; however, these NP did not selectively reduce cell viability of cancer cells. Therefore, the chromanol ring of the vitamin E analogues has an important role in the biological activity of the copolymers. Moreover, when succinate moiety is substituted and vitamin E is directly linked to the macromolecular chain through an ester bond, the biological activity is maintained., Authors acknowledge Dr. Gema Rodriǵ uez, Lautaro Biancotto, David Goḿ ez, and Rosa Ana Ramiŕ ez for their help in AFM, SEM/TEM, and cell culture experiments. Authors also thank Dr. M.P. Murphy for providing MitoQ for the experiments. This work was funded by the Spanish Ministry of Economy and Competitiveness (MAT2010−18155), Eugenio Rodriǵ uez Pascual Foundation, CIBER BBN-ECO Foundation project, and the European University of Madrid.

Nowadays, there is an increasing demand in incorporating antioxidants into biopolymeric nanoparticles (NPs) in order to enlarge their applications in the pharmaceutical and biomedical fields. The challenge of the work is to investigate the feasibility of encapsulating retinyl palmitate (RP) into chitosan (Ch) NP via ionotropic gelation. Two routes are addressed in the preparation of the systems, and they have an influence on the physicochemical properties of the NP in addition to the antioxidant amount loaded. The resulting RP-encapsulated NP has pseudo spherical morphology, average hydrodynamic diameters between 230 and 350 nm and zeta potential values between +12.5 and +30 mV, depending on RP load and procedure. Encapsulation efficiency ranges from about 35% to 64%, and the loading capacity between 4% and 10%. The antioxidant activity studied by the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay and cytotoxicity of RP-loaded NP evaluated against human dermal fibroblasts is dependent on RP content and NP concentration.

The present study deals with the design, fabrication and characterization of porous scaffolds for tissue engineering made of polylactic acid (PLA) and PLA containing hydroxyapatite (HA) nanoparticles. The main novelty relies on the fact that the fabrication of the scaffolds has been achieved avoiding totally the use of toxic chemicals. In particular, the scaffolds are obtained by combining both thermal induced phase separation (TIPS) using ethyl lactate (EL) solutions and supercritical CO2 (scCO2) drying processes. Furthermore, gelatin particles have been used as a leachable porogen and combined with the previous processes to improve the control of the pore structure features of the scaffolds. The results show that the developed technique allows for the fabrication of porous PLA scaffolds with HA concentrations up to 30 wt%. Furthermore, these scaffolds are characterized by an overall porosity as high as 98% and a double scale pore structure. In particular, the appropriate control of the TIPS process and the scCO2 drying allowed for the development of nanoscale fibrous PLA and PLA-HA structures starting from PLA/EL solutions. Concomitantly, the proper selection of the size range of gelatin particles as well as their spatial distribution in the mixture allowed imprinting an interconnected network of large pores inside the scaffolds.

Hydrogel networks that combine suitable physical and biomechanical characteristics for tissue engineering scaffolds are in demand. The aim of this work was the development of hydrogel networks based on agarose and chitosan using oxidized dextrins as low cytotoxicity crosslinking agents, paying special attention to the study of the influence of the polysaccharide composition and oxidation degree of the dextrins in the final characteristics of the network. The results show that the formation of an interpenetrating or a semi-interpenetrating polymer network was mainly dependent on a minimum agarose content and degree of oxidation of dextrin. Spectroscopic, thermal and swelling analysis revealed good compatibility with an absence of phase separation of polysaccharides at agarose:chitosan proportions of 50:50 and 25:75. The analysis of atomic force microscopy images showed the formation of a fibrillar microstructure whose distribution within the crosslinked chitosan depended mainly on the crosslinker. All materials exhibited the viscoelastic behaviour typical of gels, with a constant storage modulus independent of frequency for all compositions. The stiffness was strongly influenced by the degree of oxidation of the crosslinker. Cellular response to the hydrogels was studied with cells of different strains, and cell adhesion and proliferation was correlated with the homogeneity of the samples and their elastic properties. Some hydrogel formulations seemed to be candidates for tissue engineering applications such as wound healing or soft tissue regeneration. © 2013 Acta Materialia Inc.

Surface properties play an important role in the functioning of a biomaterial in the biological environment. This work describes the influence of the changes that occurred on diamond-like carbon (DLC) and polymeric substrata by different nitrogen and ammonia plasmas treatments and its effects on the cell proliferation on these materials. All substrata were additionally subjected to the effect of neutral beams of nitrogen atoms and NH species for comparison purposes. Results about the proliferation, viability, and morphology of fibroblasts were correlated with surface chemical composition, surface tension, and topography. It was found that the presence of amine groups on the surface and the surface tension are beneficial factors for the cell growth. Surface roughness in DLC also plays a positive role in favoring cell adhesion and proliferation, but it can be detrimental for some of the treated polymers because of the accumulation of low molecular weight fragments formed as a result of the plasma treatments. Analysis of the overall results for each type of material allowed to define a unique parameter called 'factor of merit' accounting for the influence of the different surface characteristics on the cell deployment, which can be used to predict qualitatively the efficiency for cell growth. © The Author(s) 2011.

The application of bioactive meshes in abdominal surgery for the repair of hernias is an increasing clinical activity in a wide sector of the population. The main secondary effect is the appearance of infections from bacteria, specifically Staphylococcus aureus and S. epidermidis. This paper describes the development and application of low-density polypropylene meshes coated with a biocompatible and resorbable polymer as a controlled release system of the antibiotic vancomycin. The polymeric coating (a non-cross-linked copolymer of 2-hydroxyethyl methacrylate and 2-acrylamido-2-methylpropanesulfonic acid) has a thickness of 14-15μm and contains 0.32mgcm(-2) of the antibiotic vancomycin. The in vitro experiments demonstrate the excellent inhibitory character of the coated meshes loaded with the antibiotic, following the standard protocol of inhibition of halo in agar diffusion test. This inhibitory effect is maintained for a relatively long period (at least 14days) with a low concentration of antibiotic. The acrylic polymer system regulates the release of the antibiotic with a rate of 24μgh(-1), due to its slow dissolution in the medium. Experiments in vivo, based on the implantation of coated meshes, demonstrate that the system controls the infection in the animal (rabbits) for at least 30days. The concentration of antibiotic in the blood stream of the rabbits was below the detection limit of the analytical technique (1-2μgml(-1)), which demonstrates that the antibiotic is released in the local area of the implant and remains concentrated at the implantation site, without diffusion to the blood stream. The systems can be applied to other medical devices and implants for the application of new-generation antibiotics in a controlled release and targeted applications.

12 páginas, 5 figuras, 4 tablas -- PAGS nros. 4980-4991, This paper reports the synthesis and characterization of dual functional polymerizable salts containing quaternary ammonium cations ionically linked to non steroidal anti-inflammatory drugs (NSAIDs), and their polymers and copolymeric systems obtained with acrylic monomers of different hydrophilicity, e.g. methyl methacrylate and 2-hydroxyethyl methacrylate. NSAIDs used were meclofenamic acid, ketoprofen and ibuprofen. Sustained release of the NSAID from polymeric and copolymeric samples was observed over a period of 10 days and the hydrophobic/hydrophilic character of both the polymeric system and the drug played a role in the release behaviour. The antimicrobial activity of dual functional monomeric and polymeric derivatives was confirmed against Gram-positive and Gram-negative bacteria and polymeric compounds presented higher bactericidal action than the precursory monomers. The extracts of copolymeric samples had anti-inflammatory activity in a nitric oxide inhibitory assay on RAW 264.7 cells and they produced a NO inhibition around 80% within the first seven days, This work was supported by the Ministry of Science and Innovation, (MAT2010-18155 and BIO2010-21049). N. Dinjaski thanks to the JAE-predoc program of CSIC. F. Parra and M. Fernández-Gutiérrrez also thank to the JAE-doc program of CSIC

This paper reports a biological evaluation of a nonresorbable acrylic cement loaded with alendronate for the treatment of osteoporotic vertebral compression fractures. The cement formulation was based on polymethyl methacrylate and acrylic monomers; one of these had covalently linked vitamin E residues. The same cement in the absence of alendronate was used as a control. The setting of the charged cement presented a maximum polymerization temperature of 44ºC, a setting time of 24 min, a residual monomer content lower than 3 wt.%, a compressive strength of 99±10 MPa and an elastic modulus of 1.2±0.2 GPa. Cytotoxicity studies using human osteoblast cultures revealed that the leachable substances of the alendronate loaded cement collected between 1 and 7 days decreased cell viability to values lower than 80%. However, morphological changes and cellular damage in cells produced by the extracts decreased with the leak time. Cell adhesion and growth on charged cement was significantly lower than on the control. Implantation of the cement paste in the intra-femoral cavity of rabbits showed that initially the osteogenic activity was evident for the cement charged with alendronate, and the osteosynthesis process took place mainly in the trabeculae and was manifested by the presence of a non-mineralised osseous spicule. The interface between material and adjacent bone tissue was initially characterized by a variable fibrous response that in many cases it appeared reduced to thin connective tissue after a 24-week-period, Financial support from the Comisión Interministerial de Ciencia y Tecnología, CICYT, (MAT2007-63355) is gratefully acknowledged.

This paper describes a study on the preparation and characterisation of partially biodegradable microparticles of poly(e-caprolactone)/poly(ethyl methacrylate) (PCL/PEMA) as carriers of synthetic glycolipids with antimitotic activity against brain tumour cells. Microparticles prepared by suspension polymerisation of methacrylate in the presence of already polymerised PCL showed a predominantly spherical but complex morphology, with segregation of PCL micro/nano-domains towards the surface. Small diameter discs were prepared by compression moulding of blends of microparticles and the active principle under mild conditions. The in vitro behaviour of the discs and release of the glycolipid were studied in different simulated fluid models. Ingress of fluids increased with increasing hydrophobicity of the medium. Release of the glycolipid was sustained in all fluids, the most prolonged profile being in human synovial fluid and phosphate-buffered saline modified with 20 vol.% dioxane. Slow disintegration of the discs and partial degradation of the microparticles was evident in accelerated studies. The antimitotic activity of glycolipid released from the discs was proved against a human glioblastoma line. This activity, along with selectivity against human fibroblasts, could be controlled by the amount of drug charged in the disc., This research was supported by the Comisión Interministerial de Ciencia y Tecnología (MAT2007-63355), NoE EXPERTISSUES (UE Contract No. 500283-2), CSIC (PIF 200580F0061-62-63) and a Predoctoral Fellowship from the Spanish Ministry of Science and Education (AP2005-0246). M. Fernández was supported by the Ramón y Cajal programme (MEC-Spain).

Biodegradable extracellular matrices (ECMs) consisting of mechanically stable arrays of aligned poly(lactide) nanorods (nanorod diameter ≈ 200 nm; lattice constant ≈ 500 nm) with areas up to 9 cm2 were prepared by nondestructive extraction from recyclable self-ordered nanoporous alumina hard templates. Fibroblasts formed dense tissue layers on the heparin/gelatin activated nanorod arrays, showed excellent adhesion and exhibited a highly elongated morphology such as in natural tissue. The synthetic approach reported here combining advantages of top-down lithography (well-defined topography) and self-assembly (low costs, high throughput, feature size in the 100 nm range) may yield ECMs for biomedical applications. Remarkably, on microrod arrays with four times larger feature sizes the fibroblasts were significantly less elongated and their proliferation was strongly reduced.