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.

Synthesis and Exfoliation of Calcium Organophosphonates for Tailoring Rheological Properties of Sodium Alginate Solutions: A Path toward Polysaccharide-Based Bioink.

Layered nanoparticles with surface charge are explored as rheological modifiers for extrudable materials, utilizing their ability to induce electrostatic repulsion and create a house-of-cards structure. These nanoparticles provide mechanical support to the polymer matrix, resulting in increased viscosity and storage modulus. Moreover, their advantageous aspect ratio allows for shear-induced orientation and decreased viscosity during flow. In this work, we present a synthesis and liquid-based exfoliation procedure of phenylphosphonate-phosphate particles with enhanced ability to be intercalated by hydrophilic polymers. These layered nanoparticles are then tested as rheological modifiers of sodium alginate. The effective rheological modification is proved as the viscosity increases from 101 up to 103 Pa·s in steady state. Also, shear-thinning behavior is observed. The resulting nanocomposite hydrogels show potential as an extrudable bioink for 3D printing in tissue engineering and other biomedical applications, with good shape fidelity, nontoxicity, and satisfactory cell viability confirmed through encapsulation and printing of mouse fibroblasts.

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.

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.