Potential Use In Biomedical Applications Research Articles

An environmental route of exposure affects the formation of nanoparticle coronas in blood plasma

Nanoparticles (NPs) in contact with biological fluids become covered by a tightly bound layer of proteins, the “protein corona”, and it is largely accepted that this corona gives a new identity to NPs in biological milieu. We here consider the exposing scenario of NPs through an environmental route exemplified by the use of hydrophobins, highly adhesive proteins that are secreted into the environment in large quantities by fungi. HFBII of Trichoderma reesei has been used as a model protein and we have shown strong binding to polystyrene NPs of different sizes and surface groups. Hydrophobin coated NPs are shown to strongly increase the stability and the dispersion when exposed to human plasma compared to pristine ones particles. It is also shown that the presence of hydrophobin on the NPs results in an attenuated protein corona formation, in a different corona composition, and we also show that hydrophobin remained strongly associated to the NPs in competition with plasma proteins. As a conclusion we therefore suggest that the route of exposure of nanoparticles strongly affects their surface properties and their possible physiological behavior. SignificanceThis work shows how a self-assembling protein, class II hydrophobin HFBII, with interesting biocompatible coating properties, strongly adsorbs on polystyrene NPs. HFBII is also shown to reduce aggregation of the NPs in human plasma which can increase their bioavailability with potential use in biomedical applications. The results here are also of significance for understanding possible interactions of NPs with living organisms. Hydrophobins are secreted in large quantities into the environment by fungi and this work shows how the biological environment of NPs determines the surface and colloidal properties of the particles by forming a protein corona, and that the history of the particle environment, here simulated with hydrophobin exposure, affects both plasma protein corona formation and dispersion behavior. This work thus simulates how alternative exposure routes affect nanoparticle properties, important in understanding the biological fate of NPs.

Vitroceramic interface deposited on titanium substrate by pulsed laser deposition method

Pulsed laser deposition (PLD) method was used to obtain biovitroceramic thin film coatings on titanium substrates. The composition of the targets was selected from SiO2–CaO–P2O5–(CaF2) systems and the corresponding masses were prepared using the sol–gel method. The depositions were performed in oxygen atmosphere (100mTorr), while the substrates were heated at 400°C. The PLD deposited films were analysed through different experimental techniques: X-ray diffraction, scanning (SEM, EDX) and transmission (HRTEM, SAED) electron microscopy and infra-red spectroscopy coupled with optical microscopy. They were also biologically tested by in vitro cell culture and the contact angle was determined. The bioevaluation results indicate a high biocompatibilty of the obtained materials, demonstrating their potential use for biomedical applications.

Neurite outgrowth stimulatory effects of myco synthesized AuNPs from Hericium erinaceus (Bull.: Fr.) Pers. on pheochromocytoma (PC-12) cells.

BackgroundHericium erinaceus has been reported to have a wide range of medicinal properties such as stimulation of neurite outgrowth, promotion of functional recovery of axonotmetic peroneal nerve injury, antioxidant, antihypertensive, and antidiabetic properties. In recent years, the green synthesis of gold nanoparticles (AuNPs) has attracted intense interest due to the potential use in biomedical applications. The aim of this study was to investigate the effects of AuNPs from aqueous extract of H. erinaceus on neurite outgrowth of rat pheochromocytoma (PC-12) cells.MethodsThe formation of AuNPs was characterized by UV–visible spectrum, energy dispersive X-ray (EDX), field-emission scanning electron microscope (FESEM), transmission electron microscopy (TEM), particle size distribution, and Fourier transform-infrared spectroscopy (FTIR). Furthermore, the neurite extension study of synthesized AuNPs was evaluated by in vitro assay.ResultsThe AuNPs exhibited maximum absorbance between 510 and 600 nm in UV–visible spectrum. FESEM and TEM images showed the existence of nanoparticles with sizes of 20–40 nm. FTIR measurements were carried out to identify the possible biomolecules responsible for capping and efficient stabilization of the nanoparticles. The purity and the crystalline properties were confirmed by EDX diffraction analysis, which showed strong signals with energy peaks in the range of 2–2.4 keV, indicating the existence of gold atoms. The synthesized AuNPs showed significant neurite extension on PC-12 cells. Nerve growth factor 50 ng/mL was used as a positive control. Treatment with different concentrations (nanograms) of AuNPs resulted in neuronal differentiation and neuronal elongation. AuNPs induced maximum neurite outgrowth of 13% at 600 ng/mL concentration.ConclusionIn this study, the AuNPs synthesis was achieved by a simple, low-cost, and rapid bioreduction approach. AuNPs were shown to have potential neuronal differentiation and stimulated neurite outgrowth. The water-soluble bioconstituents could be responsible for the neuroactivity. This is the first report for the biosynthesis of AuNPs using the hot aqueous extract of H. erinaceus.

Importance of refrigeration time in the electrospinning of silk fibroin aqueous solutions

Refrigeration is a common method for preserving reconstituted silk fibroin (RSF) aqueous solutions during electrospinning experiments, but the effects of preservation time at 4 °C are still not well documented. In this work, we explore its effects on the viscosity, refractive index, and density values of RSF solutions at 19 wt%. Also, extensive characterization of the mechanical properties and fiber diameters of the resulting electrospun meshes are provided. Significant differences were found in elongation, Young´s modulus, and ultimate strength at different experimental times, and an increase in the viscosity values of the RSF solutions was detected for the first 12 days of storage. These solutions exhibited a continuous, slow gelation throughout the time in storage at 4 °C, and this phenomenon improved the performance of electrospinning after a certain period of refrigeration. The protocol used reduces the production cost of SF fiber-based scaffolds and avoids the use of harsh solvents and additives which could otherwise limit their use in potential biomedical applications.

High Specific Absorption Rate and Transverse Relaxivity Effects in Manganese Ferrite Nanoparticles Obtained by an Electrochemical Route

Superparamagnetic iron oxide-based nanoparticles (SPIONS) have attracted an enormous amount of attention for their potential use in biomedical applications, due to their good biocompatibility and low toxicity. The current study considers citric acid-conjugated manganese ferrite and its synergy to be used in MRI and in hyperthermia treatment, thus showing theragnostic applications. High colloidal stability was obtained with this functionalization. SPIONS with superparamagnetic behavior of crystal sizes of approximately 20 nm were obtained via an electrochemical synthesis method. One of the highest specific absorption rate (SAR) values was achieved in this work (1661 W g–1), under a magnetic field of 30 mT at 717 kHz frequency, compared with other magnetic ferrites in the literature. These nanoparticles dissipate heat through Néel relaxation and, together with the high SAR value obtained, indicate an excellent material for hyperthermia treatment of cancer. In addition, these nanoparticles exhibit transverse relaxivity behavior, with an r2 value of 394 mM–1 s–1, i.e., at least two times higher than the value of a commercial magnetic contrast agent based on iron oxides. Finally, no toxicity effects of these nanoparticles are evidenced; as a result, these nanoparticles are appropriate for in vivo application.

Versatile side chain modification via isocyanide-based multicomponent reactions: tuning the LCST of poly(2-oxazoline)s

Poly(2-oxazoline)s are receiving large current interest based on their potential use in biomedical applications. Here we report a novel, straightforward route towards functional poly(2-oxazoline)s by Passerini and Ugi reactions.

Microstructural and Mechanical Evaluation of Laser-Assisted Cold Sprayed Bio-ceramic Coatings: Potential Use for Biomedical Applications

Bio-composite coatings of 20 wt.%, HAP and 80 wt.%, HAP were synthesized on Ti-6Al-4V substrates using LACS technique. The coatings were produced with a laser power of 2.5 kW, powder-laser spot trailing by 5 s. The coatings were analyzed for the microstructures, microhardness, composition, and bio-corrosion using SEM-EDS, XRD, hardness tester, and Metrohm PGSTAT101 machine. SEM images indicated least pores and crack-free coating with dark-spots of Ti-HAP for the 20 wt.%, HAP as opposed to the 80 wt.%, HAP coating which was solid, porous and finely cracked and had semi-melted Ti-HAP particles. The EDS mappings showed high content of HAP for the 80 wt.%, HAP coating. The diffraction patterns were similar, even though the Ti-HAP peak was broader in the 80 wt.%, HAP coating and the HAP intensities were lower for this coating except for the (004) peak. The hardness values taken at the interface inferred that the 80 wt.%, HAP coating was least bonded. It was possible to conclude that when this phase material increased the hardness dropped considerably. The bio-corrosion tests indicated that the presence of HAP in coating leads to a kinetically active coating as opposed to pure titanium coating.

Porous Chitosan Scaffolds: A Systematic Study for Choice of Crosslinker and Growth Factor Incorporation

A systematic study was conducted to evaluate the crosslinker and method of incorporation for bovine serum albumin (BSA) into chitosan hybrid scaffolds (CH-ALG) for better cartilage tissue engineering applications. Formaldehyde and sodium tripolyphosphate were used crosslinkers for fabrication of CH-ALG scaffolds using BSA as growth factor by direct incorporation and microencapsulation methods. An in vitro release study of BSA with maximum release (80%) for scaffolds of formaldehyde crosslinked was found. The present findings show that the CH-ALG hybrid scaffolds have been potential use in biomedical applications.

Tailor-made fluorescent trilobolide to study its biological relevance.

Trilobolide (Tb) is a potent natural counterpart of thapsigargin, which has shown promising results in cancer clinical trials. Here, we report a rational approach to study intracellular localization and biological activity of this sesquiterpene lactone. We conjugated Tb with a green-emitting Bodipy dye attached by alternative linkers of different lengths. The live-cell imaging of the prepared bioconjugates brought clear evidence that Tb-Bodipy localized in the endoplasmic reticulum (ER) of various cancer cell lines. The localization signal was compared with ER-specific dyes. Cytotoxicity of Tb conjugates and impact on the mitochondrial physiology and nitric oxide release were also studied. The nitric oxide production and cytokine secretion in rat peritoneal cells indicate immunobiological potential of these lactone bioconjugates. In summary, our Tb-Bodipy conjugates could help us to reveal the molecular mechanism of trilobolide for its further potential use in biomedical applications.

Simple control of surface topography of gold nanoshells by a surfactant-less seeded-growth method.

We report the synthesis of branched gold nanoshells (BGNS) through a seeded-growth surfactant-less method. This was achieved by decorating chitosan-Pluronic F127 stabilized poly(lactic-co-gycolic) acid nanoparticles (NPs) with Au seeds (NP-seed), using chitosan as an electrostatic self-assembling agent. Branched shells with different degrees of anisotropy and optical response were obtained by modulating the ratios of HAuCl4/K2CO3 growth solution, ascorbic acid (AA) and NP-seed precursor. Chitosan and AA were crucial in determining the BGNS size and structure, acting both as coreductants and structure directing growth agents. Preliminary cytotoxicity experiments point to the biocompatibility of the obtained BGNS, allowing their potential use in biomedical applications. In particular, these nanostructures with "hybrid" compositions, which combine the features of gold nanoshells and nanostars showed a better performance as surface enhanced Raman spectroscopy probes in detecting intracellular cell components than classical smoother nanoshells.

Bio-inspired Aloe vera sponges for biomedical applications

Chemical composition and biological properties of Aloe vera (AV), a tropical plant, explain its potential use for cosmetic, nutritional and biomedical applications. AV gel present in AV leaves is rich in several compounds, nutrients and polysaccharides. This work proposes using AV gel complex structure and chemical composition, associated with freeze-drying, to produce sponges. To increase the structures stability in aqueous media, a thin coating of gellan gum (GG), was applied onto AV gel. AV-based sponges showed a heterogeneous porous formation, interconnected pores and good porosity (72–77%). The coating with a GG layer onto AV influenced the stability, swelling behavior and mechanical properties of the resulting sponges. Moreover, sponges provided the sustained release of BSA-FTIC, used as a model protein, over 3 weeks. Also, in vitro cell culture studies evidenced that sponges are not cytotoxic for a mouse fibroblast-like cell line. Therefore, developed AV-based sponges have potential use in biomedical applications.

Zwitterionic hyperbranched polyester functionalized cardiovascular stent and its biocompatibility

Zwitterionic hyperbranched polyester (HBPE) synthesized on bare metal stents (BMS) surface by surface-initiated atom transfer radical polymerization (SI-ATRP) method. The modified BMS obtained was tested for its blood compatibility. The blood compatibility studies were including, platelet adhesion tests, hemolysis assay, morphological changes in RBCs, coagulation tests, PRT assay, complement activation, platelet activation, and the cytotoxicity was also investigated. The modified BMS surface does not cause platelets adherent, red blood cell disruption, hemolysis and does not induce complement and platelets activation. All results indicated that the modified BMS was blood compatible and no cytotoxicity. It has the potential use for biomedical applications.

Tribological properties of biocompatible Ti–10W and Ti–7.5TiC–7.5W

This study investigates and compares the microstructure, biocompatibility, and tribological properties of two different Ti-based composites, Ti–10W and Ti–7.5TiC–7.5W, with those of pure Ti for their potential use in biomedical applications. In particular, cold and hot isostatic-pressing and arc-melting methods were utilized and compared for the microstructure of the composites. Nano-scratch measurements and pin-on-disk wear tests were employed to understand their tribological behavior. As compared to pure Ti, Ti–10W and Ti–7.5TiC–7.5W showed significantly improved nano-scratch resistance (by 85 and 77%, respectively) and wear resistance (by 64 and 66%, respectively), in good agreement with hardness measurements. For biocompatibility examination, both microculture tetrazolium test (MTT) and water soluble tetrazolium (WST-1) test were used to quantify the cell viability of human osteoblasts and mouse fibroblasts on the materials. Both of the Ti-based composites showed acceptable biocompatibility in comparison with the pure Ti control.

Brevibacillus themoruber : a promising microbial cell factory for exopolysaccharide production

This study aims to identify a high level exopolysaccharide (EPS) producer thermophile that in turn could be used as a model organism to study the biological mechanisms and whole genome organization of EPS-producing thermophilic bacteria. Thermophilic isolates were screened, and then growth and EPS production of the best producer Brevibacillus thermoruber strain 423 were investigated under different carbon and nitrogen sources, temperature, pH and agitation rates. Rheological characterization revealed that the EPS behaved like a typical Newtonian fluid and viscosity of the EPS solution increased with increasing Ca(2+) ion concentration. Chemical characterization by TLC, GC-MS, FT-IR and NMR suggested a heteropolymer structure with glucose as major monomer unit. High biocompatibility of pure EPS fractions suggested their potential use in biomedical applications. This study reports on the comprehensive description of microbial production conditions as well as chemical, rheological and biological characterization of the EPS produced by B. thermoruber strain 423. The bioreactor cultures were found to reach two times higher yields and three times higher productivities when compared with literature. Brevibacillus thermoruber strain 423 combined the advantages of its nonpathogenicity with the advantages of fast productivity and hence proved to be a very promising model organism and cell factory for microbial EPS production.

Synthesis, characterization and bioevaluation of irinotecan-collagen hybrid materials for biomedical applications as drug delivery systems in tumoral treatments

Abstract The purpose of the present study is the preparation and characterization of collagen/antitumor drug hybrids as drug delivery systems. Materials used for obtaining collagen-based drug delivery systems were collagen type I (Coll) as matrix and irinotecan (I) as hydrophilic active substances. After incorporation of I into Coll in differing ratios, the obtained hybrid materials (Coll/I) could be used according to our results as potential drug delivery systems in medicine for the topical (local) treatment of cancerous tissues or bone. The released amount of I varies with amount of Coll from hybrid materials: the higher, the slower the release amount of irinotecan transferred is in the first 6 hours. The in vitro citotoxicity demonstrates an antitumoral activity of the obtained hybrid materials and their potential use for biomedical applications as drug delivery systems in tumoral treatments.

Screening on binary Zr–1X (X = Ti, Nb, Mo, Cu, Au, Pd, Ag, Ru, Hf and Bi) alloys with good in vitro cytocompatibility and magnetic resonance imaging compatibility

In this study, the microstructures, mechanical properties, corrosion behaviors, in vitro cytocompatibility and magnetic susceptibility of Zr–1X alloys with various alloying elements, including Ti, Nb, Mo, Cu, Au, Pd, Ag, Ru, Hf and Bi, were systematically investigated to explore their potential use in biomedical applications. The experimental results indicated that annealed Zr–1X alloys consisted entirely or primarily of α phase. The alloying elements significantly increased the strength and hardness of pure Zr and had a relatively slight influence on elastic modulus. Ru was the most effective enhancing element and Zr–1Ru alloy had the largest elongation. The results of electrochemical corrosion indicated that adding various elements to Zr improved its corrosion resistance, as indicated by the reduced corrosion current density. The extracts of the studied Zr–1X alloys produced no significant deleterious effects on osteoblast-like cells (MG 63), indicating good in vitro cytocompatibility. All except for Zr–1Ag alloy showed decreased magnetic susceptibility compared to pure Zr, and Zr–1Ru alloy had the lowest magnetic susceptibility value, being comparable to that of α′ phase Zr–Mo alloy and Zr–Nb alloy and far lower than that of Co–Cr alloy and Ti–6Al–4V alloy. Among the experimental Zr–1X alloys, Zr–1Ru alloy possessing high strength coupled with good ductility, good in vitro cytocompatibility and low magnetic susceptibility may be a good candidate alloy for medical devices within a magnetic resonance imaging environment.

Micron- and Nano-sized Poly(N-isopropylacrylamide-co-acrylic acid) Latex Syntheses and Their Applications for Controlled Drug Release

Thermo-sensitive poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAAm-co-AAc)) latex particles were prepared with and without sodium dodecyl sulfate (SDS) surfactant via an emulsion polymerization method. The P(NIPAAm-co-AAc) latex particle sizes were approximately 1.1 microm without SDS addition and the particle sizes were in the nanometer range (59 nm) with SDS at its critical micelle concentration (CMC) of 8 mM. We propose a scheme to demonstrate how the SDS concentration affects the synthesized latex particle size. The lower critical solution temperature (LCST) was hardly influenced by the SDS level but increased with the AAc concentration. The PNIPAAm-co-AAc latex particles were employed as thermo-sensitive drug carriers and 4-acetamidophenol was loaded to study the drug release rates from the nano-gels. The effective drug diffusion coefficients within the nano-gels varied as a function of particle size, AAc content, and temperature. The smaller or AAc-rich hydrogel particles provided sustainable drug release property and have potential use in biomedical applications.

Influence of electrospinning parameters on poly(hydroxybutyrate) electrospun membranes fiber size and distribution

Poly(hydroxybutyrate) (PHB) obtained from sugar cane waste was dissolved in a blend of chloroform and dimethylformamide (DMF) and electrospun at 40°C. By adding DMF to the solution, the electrospinning process for the PHB polymer becomes more stable, allowing complete polymer crystallization during the jet travelling between the tip and the grounded collector. The influence of processing parameters on fiber size and distribution was systematically studied. It was observed that an increase of tip inner diameter promotes a decrease of the fiber average size and a broader distribution. Conversely, an increase of the electric field and flow rate produces an increase of fiber diameter until a maximum of ∼2.0 µm but for electric fields higher than 1.5 kV cm−1, a decrease of the fiber diameter was observed. Polymer crystalline phase seems to be independent of the processing conditions and a crystallinity degree of 53% was found. Moreover, thermal degradation of the as‐spun membrane occurs in single step degradation with activation energy of 91 kJ mol−1. Furthermore, MC‐3T3‐E1 cell adhesion was not inhibited by the fiber mats preparation, indicating their potential use for biomedical applications. POLYM. ENG. SCI., 54:1608–1617, 2014. © 2013 Society of Plastics Engineers

Synthesis, characterization and bioevaluation of partially stabilized cements for medical applications

Abstract Materials for dental applications, i.e., white mineral trioxide aggregate (WMTA) and partial stabilized cements (PSC) were obtained using the sol-gel method. The presence of ZnO or/and CaF2 additions in the starting mixture induced changes in the composition, morphology and grindability of PSCs as compared with WMTA. The presence of foreign elements (Zn or F) in the crystalline lattice of mineralogical phases, increased their grindability. Thermal analysis (TG&DTA) was used to assess the kinetics of hydration process in binding systems based on WMTA/PSCs. The presence of foreign elements in PSCs systems increases the reactivity vs. water of these materials and consequently, the compressive strength developed after 28 days of hardening at 37°C are higher as compared with WMTA. The in vitro bioevaluation results (trypan blue staining, eukaryotic cells cycle assay by flowcytometry) accounted for a high biocompatibilty of the obtained materials demonstrating their potential use for biomedical applications.

Carbodiimide crosslinked collagen from porcine dermal matrix for high-strength tissue engineering scaffold

Naturally-derived collagens for tissue engineering are limited by low mechanical strength and rapid degradation. In this study, carbodiimide is used to chemically modify the collagen derived from porcine acellular dermal matrix (PADM). The results show that the strength and resistance of PADM to enzymatic digestion can be adjusted by the reconnection of free amino and carboxyl groups of the collagen fibers. The cytocompatibility of the crosslinked PADM was evaluated by cell adhesion and proliferation assays. The cell culture studies on crosslinked and uncrosslinked PADM showed that the modification does not affect the scaffold's biocompatibility. These results demonstrate that the PADM collagen materials can be strengthened through a low-cost, non-toxic crosslinking method for potential use in biomedical applications.