Assembling a supramolecular 3D network with tuneable mechanical properties using adamantylated cross-linking agents and ß-cyclodextrin-modified hyaluronan.

Hydrogels based on the supramolecular host-guest concept can be prepared if at least one constituent is a polymer chain modified with supramolecular host or guest (or both) units. Low-molecular-weight multitopic counterparts can also be used, however, guest molecules in the role of cross-linking agents are seldom reported, although such an approach offers wide-ranging possibilities for tuning the system properties via easily achievable structural modifications. In this paper, a series of adamantane-based star-like guest molecules was used for cross-linking of two types of ß-cyclodextrin-modified hyaluronan (CD-HA). The prepared 3D supramolecular networks were characterised using nuclear magnetic resonance, titration calorimetry and rheological measurements to confirm the formation of the host-guest complexes between adamantane moieties and ß-cyclodextrin units, including their typical properties such as self-healing and dynamic nature. The results indicate that the nature of the cross-linker (amides versus esters) has a greater impact on mechanical properties than the length of the guest's arms. In addition, the results show that the length of the HA polymer chain is more important than the degree of modification with supramolecular units. In conclusion, it was proven that the modular concept employing low-molecular-weight cross-linking guests is valuable for the formulation of supramolecular networks, including hydrogels.

Formulation of Magneto-Responsive Hydrogels from Dually Cross-Linked Polysaccharides: Synthesis, Tuning and Evaluation of Rheological Properties.

Smart hydrogels based on natural polymers present an opportunity to fabricate responsive scaffolds that provide an immediate and reversible reaction to a given stimulus. Modulation of mechanical characteristics is especially interesting in myocyte cultivation, and can be achieved by magnetically controlled stiffening. Here, hyaluronan hydrogels with carbonyl iron particles as a magnetic filler are prepared in a low-toxicity process. Desired mechanical behaviour is achieved using a combination of two cross-linking routes-dynamic Schiff base linkages and ionic cross-linking. We found that gelation time is greatly affected by polymer chain conformation. This factor can surpass the influence of the number of reactive sites, shortening gelation from 5 h to 20 min. Ionic cross-linking efficiency increased with the number of carboxyl groups and led to the storage modulus reaching 103 Pa compared to 101 Pa-102 Pa for gels cross-linked with only Schiff bases. Furthermore, the ability of magnetic particles to induce significant stiffening of the hydrogel through the magnetorheological effect is confirmed, as a 103-times higher storage modulus is achieved in an external magnetic field of 842 kA·m-1. Finally, cytotoxicity testing confirms the ability to produce hydrogels that provide over 75% relative cell viability. Therefore, dual cross-linked hyaluronan-based magneto-responsive hydrogels present a potential material for on-demand mechanically tunable scaffolds usable in myocyte cultivation.

Cross-Linked Gelatine by Modified Dextran as a Potential Bioink Prepared by a Simple and Non-Toxic Process.

Essential features of well-designed materials intended for 3D bioprinting via microextrusion are the appropriate rheological behavior and cell-friendly environment. Despite the rapid development, few materials are utilizable as bioinks. The aim of our work was to design a novel cytocompatible material facilitating extrusion-based 3D printing while maintaining a relatively simple and straightforward preparation process without the need for harsh chemicals or radiation. Specifically, hydrogels were prepared from gelatines coming from three sources-bovine, rabbit, and chicken-cross-linked by dextran polyaldehyde. The influence of dextran concentration on the properties of hydrogels was studied. Rheological measurements not only confirmed the strong shear-thinning behavior of prepared inks but were also used for capturing cross-linking reaction kinetics and demonstrated quick achievement of gelation point (in most cases < 3 min). Their viscoelastic properties allowed satisfactory extrusion, forming a self-supported multi-layered uniformly porous structure. All gelatin-based hydrogels were non-cytototoxic. Homogeneous cells distribution within the printed scaffold was confirmed by fluorescence confocal microscopy. In addition, no disruption of cells structure was observed. The results demonstrate the great potential of the presented hydrogels for applications related to 3D bioprinting.

Influence of the ß- Radiation/Cold Atmospheric-Pressure Plasma Surface Modification on the Adhesive Bonding of Polyolefins.

The goal of this research was to examine the effect of two surface modification methods, i.e., radiation cross-linking and plasma treatment, on the adhesive properties and the final quality of adhesive bonds of polypropylene (PP), which was chosen as the representative of the polyolefin group. Polymer cross-linking was induced by beta (accelerated electrons-ß-) radiation in the following dosages: 33, 66, and 99 kGy. In order to determine the usability of ß- radiation for these applications (improving the adhesive properties and adhesiveness of surface layers), the obtained results were compared with values measured on surfaces treated by cold atmospheric-pressure plasma with outputs 2.4, 4, and 8 W. The effects of both methods were compared by several parameters, namely wetting contact angles, free surface energy, and overall strength of adhesive bonds. Furthermore, Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) were conducted. According to our findings the following conclusion was reached; both tested surface modification methods significantly altered the properties of the specimen's surface layer, which led to improved wetting, free surface energy, and bond adhesion. Following the ß- radiation, the free surface energy of PP rose by 80%, while the strength of the bond grew in some cases by 290% in comparison with the non-treated surface. These results show that when compared with cold plasma treatment the beta radiation appears to be an effective tool capable of improving the adhesive properties and adhesiveness of PP surface layers.

Electrospinning of Hyaluronan Using Polymer Coelectrospinning and Intermediate Solvent.

In the current study, we present methods of sodium hyaluronate, also denoted as hyaluronan (HA), nanofiber fabrication using a direct-current (DC) electric field. HA was spun in combination with poly(vinyl alcohol) (PVA) and polyethylene oxide (PEO) and as a pure polymer. Nonaggressive solvents were used due to the possible use of the fibers in life sciences. The influences of polymer concentration, average molecular weight (Mw), viscosity, and solution surface tension were analyzed. HA and PVA were fluorescent-labeled in order to examine the electrospun structures using fluorescence confocal microscopy. In this study, two intermediate solvent mixtures that facilitate HA electrospinning were found. In the case of polymer co-electrospinning, the effect of the surfactant content on the HA/PVA electrospinning process, and the effect of HA Mw on HA/PEO nanofiber morphology, were examined, respectively.

In vivo monitoring of tumor distribution of hyaluronan polymeric micelles labeled or loaded with near-infrared fluorescence dye.

Development of delivery systems which allow real-time visual inspection of tumors is critical for effective therapy. Near-infrared (NIR) fluorophores have a great potential for such an application. To overcome NIR dyes short blood circulation time and increase tumor accumulation, a NIR dye, cypate, was associated with oleyl hyaluronan, which can self-assemble into polymeric aggregates. The cypate association with oleyl hyaluronan was performed either by a covalent linkage, or physical entrapment. The two systems were compared for tumor targeting and contrast enhancement using BALB/c mice bearing 4T1 breast cancer tumors. Independently on the way of cypate association, it took more than 24 h from intravenous administration to detect NIR signal in tumors and the tumors were clearly visualized for 2 following weeks without substrate reinjection. Covalently linked cypate generated 2-3 fold stronger fluorescence signal than physically loaded cypate. This study demonstrates the potential of HA matrix to be used as carrier of contrast agents for non-invasive long-term tumor visualization.

Hyaluronan polymeric micelles for topical drug delivery.

Nanosized materials offer promising strategy for topical drug delivery due to their enhancing effect on drug percutaneous transport across the stratum corneum barrier. In this work, polymeric micelles made from hydrophobized hyaluronic acid (HA) were probed for skin delivery. Compared to non-polymeric micelle solutions containing similar drug amount, in vitro skin penetration analysis indicated 3 times larger deposition of drug in the epidermis and 6 times larger drug deposition in the dermis after 5h of topical treatment in Franz diffusion cells. The drug deposition was further increased with prolonged time of topical treatment. Laser confocal microscopy revealed the accumulation of both, the HA forming the vehicle and the payload, in the epidermis and dermis. Although fluorescent labeling of the HA would suggest co-transport of the HA and the drug, loading FRET pair dyes in the micellar core clearly demonstrated gradual micelle disruption with increasing skin depth. Transcellular penetration was the predominant pathway for the loaded drug. The HA polymeric micelles also demonstrated increased bioactivity of loaded compound in vitro and in vivo. In addition, the loaded micelles were found to be stable in cream formulations and thus they have great potential for topical applications for cosmetic and pharmaceutical purposes.