Development of a novel NiCu nanoparticle-loaded polysaccharide-based hydrogel for 3D printing of customizable dressings with promising cytotoxicity against melanoma cells.

Polysaccharide hydrogels and metal alloy nanoparticles have already found use in a range of biomedical applications. Nickel-copper nanoparticles (NiCu NPs) are particularly promising due to their tunable properties, such as ferromagnetism, biocompatibility, and antimicrobial activity. At the same time, polysaccharide hydrogels made of polymer mixtures such as alginate and methylcellulose with incorporated metal alloy nanoparticles are reported in the scientific literature. In view of this, in this work, NiCu NPs are combined with polysaccharide hydrogels and 3D printed to construct geometrically customizable dressings with tailorable properties for melanoma treatment. This novel combination exploits the intrinsic magnetic properties of NiCu NPs and the same time builds on their less known properties to improve the mechanic stability of 3D printed materials, both contributing to a previously not reported application as potent cytotoxic dressing against melanoma cells. The dressings were evaluated in terms of their physico-chemical characteristics, and their potential application, namely melanoma cell cytotoxicity. While all dressings exhibited similar degradation profiles regardless of composition, the addition of NiCu NPs had an effect on the hydrophilicity, swelling rates, and topographical properties of the dressings. Compression results showed that the presence of NPs increased the stiffness of the dressings, while the ultimate tensile strength was highest at 0.31 MPa for the dressings with 0.5 wt% NPs. We show that although the base formulation of the dressings is biocompatible with skin-derived cells, dressings loaded with NPs exhibit promising antimelanoma activity. Extracts obtained from dressings containing 0.5 wt% NPs reduced melanoma cell viability to 61% ± 11% and 40% ± 2% after 24 h and 72 h of soaking, respectively. Furthermore, extracts of dressings with 1 wt% NPs reduced melanoma cell viability to less than 15% within the first 24 h. By adjusting the NP content, the mechanical properties, surface roughness, and wettability can be tuned so that the dressings can be functionally customized. In addition, by using 3D printing as a fabrication process, the shape and composition of the dressings can be tailored to the patient's needs. The dressings also remained intact after soaking in simulated physiological solution for 14 days, indicating their suitability for long-term topical application.

Microwave Synthesis of Poly(Acrylic) Acid-Coated Magnetic Nanoparticles as Draw Solutes in Forward Osmosis.

Polyacrylic acid (PAA)-coated magnetic nanoparticles (MNP@PAA) were synthesized and evaluated as draw solutes in the forward osmosis (FO) process. MNP@PAA were synthesized by microwave irradiation and chemical co-precipitation from aqueous solutions of Fe2+ and Fe3+ salts. The results showed that the synthesized MNPs have spherical shapes of maghemite Fe2O3 and superparamagnetic properties, which allow draw solution (DS) recovery using an external magnetic field. Synthesized MNP, coated with PAA, yielded an osmotic pressure of ~12.8 bar at a 0.7% concentration, resulting in an initial water flux of 8.1 LMH. The MNP@PAA particles were captured by an external magnetic field, rinsed in ethanol, and re-concentrated as DS in repetitive FO experiments with deionized water as a feed solution (FS). The osmotic pressure of the re-concentrated DS was 4.1 bar at a 0.35% concentration, resulting in an initial water flux of 2.1 LMH. Taken together, the results show the feasibility of using MNP@PAA particles as draw solutes.

Superparamagnetic Fe3O4@CA Nanoparticles and Their Potential as Draw Solution Agents in Forward Osmosis.

In this study, citric acid (CA)-coated magnetite Fe3O4 magnetic nanoparticles (Fe3O4@CA MNPs) for use as draw solution (DS) agents in forward osmosis (FO) were synthesized by co-precipitation and characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), dynamic light scattering (DLS), transmission electron microscopy (TEM) and magnetic measurements. Prepared 3.7% w/w colloidal solutions of Fe3O4@CA MNPs exhibited an osmotic pressure of 18.7 bar after purification without aggregation and a sufficient magnetization of 44 emu/g to allow DS regeneration by an external magnetic field. Fe3O4@CA suspensions were used as DS in FO cross-flow filtration with deionized (DI) water as FS and with the active layer of the FO membrane facing the FS and NaCl as a reference DS. The same transmembrane bulk osmotic pressure resulted in different water fluxes for NaCl and MNPs, respectively. Thus the initial water flux with Fe3O4@CA was 9.2 LMH whereas for 0.45 M NaCl as DS it was 14.1 LMH. The reverse solute flux was 0.08 GMH for Fe3O4@CA and 2.5 GMH for NaCl. These differences are ascribed to a more pronounced internal dilutive concentration polarization with Fe3O4@CA as DS compared to NaCl as DS. This research demonstrated that the proposed Fe3O4@CA can be used as a potential low reverse solute flux DS for FO processes.

Intervertebral disc tissue engineering: A brief review.

Intervertebral disc (IVD) degeneration (IDD) is associated with low back pain and significantly affects the patient's quality of life. Degeneration of the IVD alters disk height and the mechanics of the spine, leading to chronic segmental spinal instability. The pathophysiology of IVD disease is still not well understood. Current therapies for IDD include conservative and invasive approaches, but none of those treatments are able to restore the disc structure and function. Recently, tissue engineering techniques emerged as a possible approach to treat IDD, by replacing a damaged IVD with scaffolds and appropriate cells. Advances in manufacturing techniques, material processing and development, surface functionalization, drug delivery systems and cell incorporation furthered the development of tissue engineering therapies. In this review, biomaterial scaffolds and cell-based therapies for IVD regeneration are briefly discussed.

A green approach to obtain stable and hydrophilic cellulose-based electrospun nanofibrous substrates for sustained release of therapeutic molecules.

Stable and (bio)-compatible nanofibrous matrices showing effective incorporation and release of nonsteroidal anti-inflammatory drugs (NSAIDs) hold a huge potential in tissue regeneration and wound healing. Herein, a two-step, water-based and needleless electrospinning method is used to fabricate thermally cross-linked multifunctional nanofibrous substrates from a hydrophilic cellulose derivative, i.e. carboxymethyl cellulose (CMC), and polyethylene glycol (PEG) with an in situ incorporated NSAID, diclofenac (DCF). Electrospun bi-component blend nanofibers, strongly linked together by ester bonds, with different degrees of cross-linking density are achieved by varying the concentrations of butanetetracarboxylic acid (BTCA, a green polycarboxylic cross-linker) and the sodium hypophosphite (SHP) catalyst, and the temperature. The results demonstrated that not only the dimensional stability and swelling properties could be better controlled but also the morphology, fiber diameter, surface area, pore volume, pore size, and functionality of the cross-linked nanofibers. Release kinetics of DCF from the nanofibrous substrates are controlled and prolonged up to 48 h, and the overall released mass of DCF decreased linearly with increasing cross-linking degree of BTCA and SHP. Fitting of release data using various kinetic models revealed that the release of DCF follows a non-Fickian (diffusion and erosion controlled) to Fickian mechanism (only diffusion-controlled process). Cell viability testing based on crystal violet dyeing showed that the DCF-incorporating nanofibers have excellent biocompatibility and no toxic effect on human skin fibroblast cells. Overall, the reported DCF-incorporating nanofibrous substrate demonstrates high potential to be used as a smart drug delivery system in wound healing, especially due to its noninvasive characteristics.

Multilayered Polysaccharide Nanofilms for Controlled Delivery of Pentoxifylline and Possible Treatment of Chronic Venous Ulceration.

Local drug delivery systems made from nontoxic polysaccharide nanofilms have an enormous potential in wound care. A detailed understanding of the structural, surface, physicochemical, and cytotoxic properties of such systems is crucial to design clinically efficacious materials. Herein, we fabricated polysaccharide-based nanofilms onto either a 2D model (SiO2 and Au sensors) or on nonwoven alginate 3D substrates using an alternating assembly of N,N,N-trimethylchitosan (TMC) and alginic acid (ALG) by a spin-assisted layer-by-layer (LbL) technique. These TMC/ALG multilayered nanofilms are used for a uniform encapsulation and controlled release of pentoxifylline (PTX), a potent anti-inflammatory drug for treatment of the chronic venous ulceration. We show a tailorable film growth and mass, morphology, as well as surface properties (charge, hydrophilicity, porosity) of the assembled nanofilms through control of the coating during the spin-assisted assembly. The uniform distribution of the encapsulated PTX in the TMC/ALG nanofilms is preserved even with when the amount of the incorporated PTX increases. The PTX release mechanism from the model and real systems is studied in detail and is very comparable for both systems. Finally, different cell-based assays illustrated the potential of the TMC/ALG multilayer system in wound care (e.g., treatment chronic venous ulceration) applications, including a decrease of TNF-α secretion, a common indicator of inflammation.

Novel chitosan/diclofenac coatings on medical grade stainless steel for hip replacement applications.

Corrosion resistance, biocompatibility, improved osteointegration, as well the prevention of inflammation and pain are the most desired characteristics of hip replacement implants. In this study we introduce a novel multi-layered coating on AISI 316LVM stainless steel that shows promise with regard to all mentioned characteristics. The coating is prepared from alternating layers of the biocompatible polysaccharide chitosan and the non-steroid anti-inflammatory drug (NSAID), diclofenac. Electrochemical methods were employed to characterize the corrosion behavior of coated and uncoated samples in physiological solution. It is shown that these coatings improve corrosion resistance. It was also found that these coatings release the incorporated drug in controlled, multi-mechanism manner. Adding additional layers on top of the as-prepared samples, has potential for further tailoring of the release profile and increasing the drug dose. Biocompatibility was proven on human-derived osteoblasts in several experiments. Only viable cells were found on the sample surface after incubation of the samples with the same cell line. This novel coating could prove important for prolongation of the application potential of steel-based hip replacements, which are these days often replaced by more expensive ceramic or other metal alloys.

Synthesis of chromium-nickel nanoparticles prepared by a microemulsion method and mechanical milling.

A chemical and a physical method have been applied for the preparation of chromium-nickel alloy nanoparticles. These particles were designed to be used for controlled magnetic hyperthermia applications. Microemulsions with Ni2+ and Cr3+ and/or NaBH4 as precursors were prepared using the isooctane/CTAB, n-butanol/H2O system. The samples of CrxNi1-x nanoparticles with the desired composition were obtained after the reduction of their salts with NaBH4 and afterwards heat treated in a TGA in a N2 atmosphere at various temperatures. The CrxNi1-x materials were also prepared by mechanical milling. Utilizing a ball-to-powder mass ratio of 20 : 1 and selecting the proper alloy compositions we were able to obtain nanocrystalline CrxNi1-x particles. Thermal demagnetization in the vicinity of the Curie temperature of the nanoparticles was studied using a modified TGA-SDTA method. The alloy's phase composition, size and morphology were determined with XRD measurements and TEM analyses.

A facile route to the synthesis of coated maghemite nanocomposites for hyperthermia applications.

CM-dextran-covered maghemite particles for applications in magnetic hyperthermia treatments were synthesized and their physical, magnetic and morphological properties were examined. Magnetic fluids were prepared and their heating properties in an alternating magnetic field were studied. The results reveal that the particle size and the thickness of the carboxy-methyl-dextran (CM-dextran) coatings have a decisive influence on the heating properties: specific absorption rate (SAR). The majority of the magnetic dissipation comes from the Neel relaxation, while the Brown contribution is small. A thermal steady state at the selected temperature (42 °C) can be achieved using synthesized maghemite particles with proper particle morphology and by controlling the magnetic field intensity or the frequency.