Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (P(3HB-co-3HV))/Bacterial Cellulose (BC) Biocomposites for Potential Use in Biomedical Applications.

The aim of this study was to obtain biocomposites consisting of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), bacterial cellulose (BC) and α-tocopherol by a melt processing technique for potential use in biomedical applications. The melt processing and roughness of biocomposites were evaluated and compared to sample without BC. The degradation rate of PHBV/BC biocomposites was measured in phosphate buffer saline (PBS) by determining the mass variation and evidencing of thermal and structural changes by differential scanning calorimetry (DSC) and attenuated total reflectance-Fourier transformed infrared spectrometry (ATR-FTIR). The cell viability, cell morphology, cell cycle distribution and total collagen content were investigated on murine NCTC fibroblasts. Overall, the adding of BC to polyester matrix led to an adequate melt processing of biocomposites and increased surface roughness and cytocompatibility, allowing the cells to secrete the extracellular matrix (collagen) and stimulate cell proliferation. Results showed that the PHBV/BC biocomposites were favorable for long-term degradation and could be used for the design of medical devices with controlled degradability.

Mechanical and Wetting Properties of Ta2O5 and ZnO Coatings on Alloy Substrate of Cardiovascular Stents Manufactured by Casting and DMLS.

In the last years, additive manufacturing technologies have been developed, especially direct metal laser sintering, and used in the dental and medical implant domains. Cardiovascular stents have evolved from bioinert, bare metal cages to biomimetic devices that promote tissue regeneration or healing. In this paper, comparisons concerning mechanical properties between Co-Cr alloy and cast 304L stainless steel were realized using FEM analysis, necessary for manufacturing cardiovascular stents by DMLS technology using Co-Cr alloy. The purpose of this paper consists of the evaluation of the contact angle at the interface of the Co-Cr alloy manufactured by DMLS, respectively, cast stainless steel 304L, and thin film deposition realized by the e-gun method (Ta2O5 and ZnO). Scanning electronic microscopy SEM and EDX techniques were employed for morphological investigation of the sintered samples manufactured by the DMLS process. They were also used for semi-quantitative and qualitative chemical and metallographic analyses. The e-gun coating was used to obtain thin films with the nanometer order of Ta2O5 and ZnO with a protective role to improve the corrosion resistance, roughness, and antiseptic role.

Applications of Polymers for Organ-on-Chip Technology in Urology.

Organ-on-chips (OOCs) are microfluidic devices used for creating physiological organ biomimetic systems. OOC technology brings numerous advantages in the current landscape of preclinical models, capable of recapitulating the multicellular assemblage, tissue-tissue interaction, and replicating numerous human pathologies. Moreover, in cancer research, OOCs emulate the 3D hierarchical complexity of in vivo tumors and mimic the tumor microenvironment, being a practical cost-efficient solution for tumor-growth investigation and anticancer drug screening. OOCs are compact and easy-to-use microphysiological functional units that recapitulate the native function and the mechanical strain that the cells experience in the human bodies, allowing the development of a wide range of applications such as disease modeling or even the development of diagnostic devices. In this context, the current work aims to review the scientific literature in the field of microfluidic devices designed for urology applications in terms of OOC fabrication (principles of manufacture and materials used), development of kidney-on-chip models for drug-toxicity screening and kidney tumors modeling, bladder-on-chip models for urinary tract infections and bladder cancer modeling and prostate-on-chip models for prostate cancer modeling.

Silk ProteinsEnriched Nanocomposite Hydrogels Based on Modified MMT Clay and Poly(2-hydroxyethyl methacrylate-co-2-acrylamido-2-methylpropane Sulfonic Acid) Display Favorable Properties for Soft Tissue Engineering.

Due to their remarkable structures and properties, three-dimensional hydrogels and nanostructured clay particles have been extensively studied and have shown a high potential for tissue engineering as solutions for tissue defects. In this study, four types of 2-hydroxyethyl methacrylate/2-acrylamido-2-methylpropane sulfonic acid/montmorillonite (HEMA/AMPSA/MMT) hydrogels enriched with sericin, and fibroin were prepared and studied in the context of regenerative medicine for soft tissue regenerative medicine. Our aim was to obtain crosslinked hydrogel structures using modified montmorillonite clay as a crosslinking agent. In order to improve the in vitro and in vivo biocompatibility, silk proteins were further incorporated within the hydrogel matrix. Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR) were performed to prove the chemical structures of the modified MMT and nanocomposite hydrogels. Swelling and rheological measurements showed the good elastic behavior of the hydrogels due to this unique network structure in which modified MMT acts as a crosslinking agent. Hydrogel biocompatibility was assessed by MTT, LDH and LIVE/DEAD assays. The hydrogels were evaluated for their potential to support adipogenesis in vitro and human stem cells isolated from adipose tissue were seeded in them and induced to differentiate. The progress was assessed by evaluation of expression of adipogenic markers (ppar-γ2, perilipin) evaluated by qPCR. The potential of the materials to support tissue regeneration was further evaluated on animal models in vivo. All materials proved to be biocompatible, with better results on the 95% HEMA 5% AMPSA enriched with sericin and fibroin material. This composition promoted a better development of adipogenesis compared to the other compositions studied, due the addition of sericin and fibroin. The results were confirmed in vivo as well, with a better progress of soft tissue regeneration after implantation in mice. Therefore, hydrogel 95% HEMA 5% AMPSA enriched with sericin as well as fibroin showed the best results that recommend it for future soft tissue engineering application.

Novel chitosan and bacterial cellulose biocomposites tailored with polymeric nanoparticles for modern wound dressing development.

Dressing biomaterials play a key role in wound management keeping a moisture medium and protecting against external factors. Natural and synthetic materials could be used as dressings where chitosan and bacterial cellulose is one of the most important solutions. These biopolymers have been used for wound dressing based on their non-toxic, biodegradable, and biocompatible features. In this study, biocomposites based on bacterial cellulose and chitosan membranes tailored with antimicrobial loaded poly(N-isopropylacrylamide)/polyvinyl alcohol nanoparticles were prepared. Core-shell polymeric nanoparticles, bacterial cellulose/chitosan membranes, and biocomposites were independently loaded with silver sulfadiazine, a well-known sulfonamide antibacterial agent used in the therapy of mild-to-moderate infections for sensitive organisms. The chemistry, structure, morphology, and size distribution were investigated by Fourier transformed infrared spectroscopy (FTIR-ATR), RAMAN spectroscopy, Scanning electron (SEM) and Transmission electron microscopy (TEM), and Dynamic light scattering (DLS). In vitro release behaviors of silver sulfadiazine from polymeric nanoparticles and biocomposites were investigated. The biological investigations revealed good biocompatibility of both the nanoparticles and the biocomposites in terms of human dermal fibroblasts viability and proliferation potential. Finally, the drug-loaded polymeric biomaterials showed promising characteristics, proving their high potential as an alternative support to develop a biocompatible and antibacterial wound dressing.

In Vitro Interaction of Doxorubicin-Loaded Silk Sericin Nanocarriers with MCF-7 Breast Cancer Cells Leads to DNA Damage.

In this paper, Bombyx mori silk sericin nanocarriers with a very low size range were obtained by nanoprecipitation. Sericin nanoparticles were loaded with doxorubicin, and they were considered a promising tool for breast cancer therapy. The chemistry, structure, morphology, and size distribution of nanocarriers were investigated by Fourier transformed infrared spectroscopy (FTIR-ATR), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and dynamic light scattering (DLS). Morphological investigation and DLS showed the formation of sericin nanoparticles in the 25-40 nm range. FTIR chemical characterization showed specific interactions of protein-doxorubicin-enzymes with a high influence on the drug delivery process and release behavior. The biological investigation via breast cancer cell line revealed a high activity of nanocarriers in cancer cells by inducing significant DNA damage.

Current Landscape in Organic Nanosized Materials Advances for Improved Management of Colorectal Cancer Patients.

Globally, colorectal cancer (CRC) ranks as one of the most prevalent types of cancers at the moment, being the second cause of cancer-related deaths. The CRC chemotherapy backbone is represented by 5-fluorouracil, oxaliplatin, irinotecan, and their combinations, but their administration presents several serious disadvantages, such as poor bioavailability, lack of tumor specificity, and susceptibility to multidrug resistance. To address these limitations, nanomedicine has arisen as a powerful tool to improve current chemotherapy since nanosized carriers hold great promise in improving the stability and solubility of the drug payload and enhancing the active concentration of the drug that reaches the tumor tissue, increasing, therefore, the safety and efficacy of the treatment. In this context, the present review offers an overview of the most recent advances in the development of nanosized drug-delivery systems as smart therapeutic tools in CRC management and highlights the emerging need for improving the existing in vitro cancer models to reduce animal testing and increase the success of nanomedicine in clinical trials.

Bio- and Hemo-Compatible Silk Fibroin PEGylated Nanocarriers for 5-Fluorouracil Chemotherapy in Colorectal Cancer: In Vitro Studies.

5-fluorouracil (5-FU) remains the gold standard of treatment for colorectal cancer, but its poor bioavailability and high systemic toxicity highlight the urgent need for the development of novel delivery strategies to increase the efficacy of 5-FU treatment. The present study is aimed to design and validate a PEGylated Silk Fibroin Nanocarrier (SF/PEG nanoparticles (NPs)) as an efficient 5-FU delivery system for potential intravenous administration. Using the human adenocarcinoma HT-29 cell line as an in vitro model for colorectal cancer, the cytotoxicity screening of the SF/PEG NPs showed that pristine nanocarriers were highly biocompatible, while the addition of 5-FU triggers a dramatic reduction in tumor cell viability, proliferation potential and mitochondrial integrity as well as a significant increase in nitric oxide production. Despite their high in vitro cytotoxicity, the 5-FU SF/PEG NPs were found hemocompatible as no impact on red blood cells hemolysis or the phagocytic activity of the granulocytes was observed. Exposure of HT-29 tumor cells and blood samples to 5-FU SF/PEG NPs augmented the tumor necrosis factor-α levels. Moreover, 5-FU SF/PEG NPs showed an impact on tumor cell migration and invasive potential as both of these processes were inhibited by the NP treatment.

Assessment of Naturally Sourced Mineral Clays for the 3D Printing of Biopolymer-Based Nanocomposite Inks.

The present study investigated the possibility of obtaining 3D printed composite constructs using biomaterial-based nanocomposite inks. The biopolymeric matrix consisted of methacrylated gelatin (GelMA). Several types of nanoclay were added as the inorganic component. Our aim was to investigate the influence of clay type on the rheological behavior of ink formulations and to determine the morphological and structural properties of the resulting crosslinked hydrogel-based nanomaterials. Moreover, through the inclusion of nanoclays, our goal was to improve the printability and shape fidelity of nanocomposite scaffolds. The viscosity of all ink formulations was greater in the presence of inorganic nanoparticles as shear thinning occurred with increased shear rate. Hydrogel nanocomposites presented predominantly elastic rather than viscous behavior as the materials were crosslinked which led to improved mechanical properties. The inclusion of nanoclays in the biopolymeric matrix limited hydrogel swelling due the physical barrier effect but also because of the supplementary crosslinks induced by the clay layers. The distribution of inorganic filler within the GelMA-based hydrogels led to higher porosities as a consequence of their interaction with the biopolymeric ink. The present study could be useful for the development of soft nanomaterials foreseen for the additive manufacturing of customized implants for tissue engineering.

Novel Nanocomposites Based on Bacterial Polyester/LDH-SDS Clay for Stem Cells Delivery in Modern Wound Healing Management.

Nanocomposite materials based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) and modified mineral clay layered double hydroxides (LDH-SDS) were explored as novel nanostructured materials for potential tissue engineering applications. The mineral clay inorganic phase was modified with an anionic long-chain structure of carbon atoms, such as sodium dodecyl sulfate, in order to increase the compatibility between the two phases. The melt intercalation method used for nanocomposite fabrication ensures a good dispersion of the modified LDH-SDS within the polymer matrix without using a toxic solvent (chloroform). The nanocomposites were found to have an intercalated/exfoliated structure with an enhanced Young modulus and increased stiffness. This could allow them to be considered for autologous stem cells dressings in the view of efficient wound healing applications.

Bacterial Cellulose-Modified Polyhydroxyalkanoates Scaffolds Promotes Bone Formation in Critical Size Calvarial Defects in Mice.

Bone regeneration is a claim challenge in addressing bone defects with large tissue deficits, that involves bone grafts to support the activity. In vitro biocompatibility of the bacterial cellulose-modified polyhydroxyalkanoates (PHB/BC) scaffolds and its osteogenic potential in critical-size mouse calvaria defects had been investigated. Bone promotion and mineralization were analyzed by biochemistry, histology/histomorphometry, X-ray analysis and immunofluorescence for highlighting osteogenesis markers. In summary, our results showed that PHB/BC scaffolds are able to support 3T3-L1 preadipocytes proliferation and had a positive effect on in vivo osteoblast differentiation, consequently inducing new bone formation after 20 weeks post-implantation. Thus, the newly developed PHB/BC scaffolds could turn out to be suitable biomaterials for the bone tissue engineering purpose.

Impact of the magnetic field on 3T3-E1 preosteoblasts inside SMART silk fibroin-based scaffolds decorated with magnetic nanoparticles.

This paper reports the impact of the magnetic field on 3T3-E1 preosteoblasts within silk-fibroin scaffolds decorated with magnetic nanoparticles. Scaffolds were prepared from silk fibroin and poly(2-hydroxyethyl methacrylate) template in which magnetite nanoparticles were embedded. The presence of the magnetite specific peaks within scaffolds compositions was evidenced by RAMAN analysis. Structural investigation was done by XRD analysis and morphological information including internal structure was obtained through SEM analysis. Geometrical evaluation (size and shape), crystalline structure of magnetic nanoparticles and the morphology of the silk fibroin scaffolds were investigated by HR-TEM. Magnetic nanoparticles were distributed within scaffolds structure. Biomineralization of hydroxyapatite on silk fibroin scaffolds with and without magnetic nanoparticles was investigated by an alternate soaking process. SEM images showed that the magnetic scaffolds were covered in an almost continuously film, which has a phase with nanostructured characteristics. This phase, which has as main components Ca and P, is made of lamellar formations. The design of an original magnetic 3D cell culture setup allowed us to observe cellular modifications under the exposure to magnetic field in the presence of magnetic silk fibroin biomaterials. The cellular proliferation potential of 3T3-E1 cell line was found increased under the magnetic field, especially in the presence of the magnetite nanoparticles. In addition, we showed that the low static magnetic field positively impacts on the osteogenic differentiation potential of the cells inside the biomimetic magnetic scaffolds.

Grafting versus Crosslinking of Silk Fibroin-g-PNIPAM via Tyrosine-NIPAM Bridges.

This paper reports the synthesis and complex characterization of novel polymeric networks based on the crosslinking of Bombyx mori silk fibroin via poly(N-isopropylacrylamide) bridges generated by an ammonium cerium nitrate redox system. The research study gives an understanding of the polymerization mechanism in terms of the generation of radical sites, radical growth and termination reaction, as well as the involvement of modifications on silk fibroin structure and properties. The physico-chemical characterization was carried out by FTIR-ATR, X-ray photoelectron spectroscopy and RAMAN spectroscopy with unravelling the chemical modification. The structural characterization and spatial arrangement by secondary structure were carried out by X-ray diffraction and circular dichroism. The thermal behavior and thermal stability were evaluated by differential scanning calorimetry and thermogravimetric analysis. The novel complex polymer network is intended to be used in the field of smart drug delivery systems.

Novel Nanocomposites Based on Functionalized Magnetic Nanoparticles and Polyacrylamide: Preparation and Complex Characterization.

This paper reports the synthesis and complex characterization of nanocomposite hydrogels based on polyacrylamide and functionalized magnetite nanoparticles. Magnetic nanoparticles were functionalized with double bonds by 3-trimethoxysilyl propyl methacrylate. Nanocomposite hydrogels were prepared by radical polymerization of acrylamide monomer and double bond modified magnetite nanoparticles. XPS spectra for magnetite and modified magnetite were recorded to evaluate the covalent bonding of silane modifying agent. Swelling measurements in saline solution were performed to evaluate the behavior of these hydrogels having various compositions. Mechanical properties were evaluated by dynamic rheological analysis for elastic modulus and vibrating sample magnetometry was used to investigate the magnetic properties. Morphology, geometrical evaluation (size and shape) of nanostructural characteristics and the crystalline structure of the samples were investigated by SEM, HR-TEM and selected area electron diffraction (SAED). The nanocomposite hydrogels will be further tested for the soft tissue engineering field as repairing scaffolds, due to their mechanical and magnetization behavior that can stimulate tissue regeneration.

Methods of synthesis, properties and biomedical applications of polyhydroxyalkanoates: a review.

This study aims to provide an overview of the main polyhydroxyalkanoates (PHAs) used in medical applications. In this review, it has been demonstrated that the properties of PHAs can be controlled both by varying the concentration of units in the copolymer and the substrate for PHA production. Another way of controlling the mechanical properties of PHAs is varying the 3HV content, such as the case of P(3HB-co-3HV). A higher 3HV content in the structure of this polyester will lead to a lower cristallinity and, therefore, to greater flexibility, strength and elongation at break. PHAs are biocompatible, completely biodegradable, and non-toxic. Considering the state of the art technologies and their ideal properties, PHAs (especially the short-chain-length PHA polymers) can be tailored for specific medical applications, such as surgical suture, scaffolds, grafts and heart valves or drug delivery systems. Nowaday, random copolyesters of 3HB and 4HB (P(3HB-co-4HB)) are used for the development of biodegradable implants loaded with antibiotics for therapeutic treatment of chronic osteomyelitis. It is also believed that these biodegradable materials can be efficient alternatives for reducing the pollution produced by the medical waste consisting of replacing plastic handles, packs, syringes or tubes that are trashed into the homes, clinics and hospitals around the world.

Poly(3-hydroxybutyrate-CO-3-hydroxyvalerate) PHBHV biocompatible nanocarriers for 5-FU delivery targeting colorectal cancer.

Aiming to address the issue of poor bioavailability of most anti-tumor medicines against colorectal cancer, we developed a targeted anticancer nanocarrier using biocarriers able to both bind and easily release their load in a controlled manner. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) carriers were obtained via the emulsification-diffusion method, loaded with 5-fluorouracil and then characterized in terms of particle morphology and size (SEM, DLS), drug uptake and release. The cytotoxic potential of the 5-fluorouracil-loaded polymer nanocarriers on human adenocarcinoma cells (HT-29 cell line) was investigated. The in vitro studies clearly demonstrated that while the nanocarriers themselves slightly alter HT-29 cell viability, when loaded with 5-fluorouracil they significantly decrease cell viability, suggesting that the polymer itself exhibits low cytotoxicity and the drug-loaded carrier acts in an efficient manner to kill HT-29 human adenocarcinoma cells.

Potential Use in Forensics of a Novel Hybrid Gelatin-Dynamic Impact Assessment.

Ballistic gelatin as simulant of the human body and organs is a support in forensics. After having obtained very good results for a new gelatin-based composite in terms of physicochemical and rheological properties, this study focused on this material's mechanical behavior during stabbing and shooting versus bovine and porcine organs and standard ballistic gelatin. The hybrid gelatin has a predominantly elastic behavior at 23°C, whereas the elastic modulus becomes practically constant in the 10-0.1 Hz frequency range. In terms of stabbing behavior, the small variations obtained between porcine organs and surrogate are below 5%, the perforation indicating a good similarity. From the ballistic test results using 10 × 28T rubber balls, it has been seen that the hybrid ballistic gelatin conducts to more reliable and reproducible values of perforation/penetration versus standard gelatin, making from it a real candidate for use in forensic tests.

Poly(HydroxyButyrate-co-HydroxyValerate) (PHBHV) Nanocarriers for Silymarin Release as Adjuvant Therapy in Colo-rectal Cancer.

The aim of this study was to address one of the major challenges of the actual era of nanomedicine namely, the bioavailability of poorly water soluble drugs such as Silymarin. We developed new, biodegradable, and biocompatible nanosized shuttles for Silymarin targeted delivery in colon-cancer cells. The design of these 100 nm sized carrier nanoparticles was based on natural polymers and their biological properties such as cellular uptake potential, cytotoxicity and 3D penetrability were tested using a colon cancer cell line (HT-29) as the in vitro culture model. Comparative scanning electron microscopy (SEM) and atomic force microscopy (AFM) measurements demonstrated that the Silymarin loaded Poly(3-HydroxyButyrate-co-3-HydroxyValerate) (PHBHV) nanocarriers significantly decreased HT-29 cells viability after 6 and 24 h of treatment. Moreover, in vivo-like toxicity studies on multicellular tumor spheroids showed that the Silymarin loaded PHBHV nanocarriers are able to penetrate 3D micro tumors and significantly reduce their size.

Novel formulations of ballistic gelatin. 1. Rheological properties.

Ballistic gelatin is the simulant of the human body during field tests in forensics and other related fields, due to its physical and mechanical similarities to human trunk and organs. Since the ballistic gelatin used in present has important issues to overcome, an alternative approach is the use of gelatin-polymer composites, where a key factor is the insertion of biocompatible materials, which replicate accurately the human tissues. In order to be able to obtain an improved material in terms of mechanical performances by an easy industrial-scale technology, before the verification of the ballistic parameters by shooting in agreement with military standards, one of the best and cheapest solutions is to perform a thorough check of their rheological properties, in standard conditions.

Evidence-based Neuro Linguistic Psychotherapy: a meta-analysis.

BACKGROUND: Neuro Linguistic Programming (NLP) Framework has enjoyed enormous popularity in the field of applied psychology. NLP has been used in business, education, law, medicine and psychotherapy to identify people's patterns and alter their responses to stimuli, so they are better able to regulate their environment and themselves. NLP looks at achieving goals, creating stable relationships, eliminating barriers such as fears and phobias, building self-confidence, and self-esteem, and achieving peak performance. Neuro Linguistic Psychotherapy (NLPt) encompasses NLP as framework and set of interventions in the treatment of individuals with different psychological and/or social problems. We aimed systematically to analyse the available data regarding the effectiveness of Neuro Linguistic Psychotherapy (NLPt). SUBJECTS AND METHODS: The present work is a meta-analysis of studies, observational or randomized controlled trials, for evaluating the efficacy of Neuro Linguistic Programming in individuals with different psychological and/or social problems. The databases searched to identify studies in English and German language: CENTRAL in the Cochrane Library; PubMed; ISI Web of Knowledge (include results also from Medline and the Web of Science); PsycINFO (including PsycARTICLES); Psyndex; Deutschsprachige Diplomarbeiten der Psychologie (database of theses in Psychology in German language), Social SciSearch; National library of health and two NLP-specific research databases: one from the NLP Community (http://www.nlp.de/cgi-bin/research/nlprdb.cgi?action=res_entries) and one from the NLP Group (http://www.nlpgrup.com/bilimselarastirmalar/bilimsel-arastirmalar-4.html#Zweig154). RESULTS: From a total number of 425 studies, 350 were removed and considered not relevant based on the title and abstract. Included, in the final analysis, are 12 studies with numbers of participants ranging between 12 and 115 subjects. The vast majority of studies were prospective observational. The actual paper represents the first meta-analysis evaluating the effectiveness of NLP therapy for individuals with social/psychological problems. The overall meta-analysis found that the NLP therapy may add an overall standardized mean difference of 0.54 with a confidence interval of CI=[0.20; 0.88]. CONCLUSION: Neuro-Linguistic Psychotherapy as a psychotherapeutic modality grounded in theoretical frameworks, methodologies and interventions scientifically developed, including models developed by NLP, shows results that can hold its ground in comparison with other psychotherapeutic methods.