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

Abstract

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.

Recent advances in responsive hydrogels for diabetic wound healing

“…Recently, smart hydrogels with stimulus-responsive functions have attracted considerable attention. Briefly, stimulus-responsive hydrogels can respond to internal physiological signals (i.e., temperature [ 28 , 29 ], pH [ 30 , 31 ], redox [ 32 , 33 ], glucose [ 34 , 35 ], or enzymes [ 36 , 37 ]), external stimuli (i.e., temperature [ 38 , 39 ], magnetic field [ 40 , 41 ], pressure [ 42 , 43 ], reactive oxygen species (ROS) [ 44 , 45 ], light [ 46 , 47 ] and electric field [ 48 , 49 ]) or a combination of the above, which can reversibly or irreversibly change the physical properties or chemical structure ( Fig. 2 ).…”

Statistical optimization of hydrazone-crosslinked hyaluronic acid hydrogels for protein delivery

“…36 In comparison, our HA hydrogels exhibited relatively low compressive moduli within a narrow range of 4.5-42.2 Pa. Others have found that a higher degree of modification for HA-ADH led to stiffer hydrogels, which was similar to what we observed for the 40 kDa hydrogels. 35 Ultimately, our method of fabricating hydrazone-crosslinked HA hydrogels yielded hydrogels with a wide range of physicochemical properties, including large ranges in hydrogel gelation time and mass change, with the capacity to swell, degrade, or maintain a relatively constant mass over 28 days depending on the molecular weight and concentrations of HA-ADH and HA-Ox used (Table 2).…”

“…[30][31][32] We formed HA hydrogels using dynamic covalent hydrazone crosslinks as this approach can yield a wide range of physicochemical properties, making them an attractive hydrogel platform for numerous regenerative medicine applications. [33][34][35][36][37][38][39][40] The properties of hydrazone-crosslinked HA hydrogels can be easily tuned by adjusting the ratios of the two dynamic covalent crosslinking polymers: oxidized HA (HA-Ox) and HA adipic acid dihydrazide (HA-ADH). Thus, we narrowed our input parameters to HA molecular weight, HA-Ox concentration, and HA-ADH concentration.…”

Recent Advances in the Degradability and Applications of Tissue Adhesives Based on Biodegradable Polymers

“…This type of crosslinking can be controlled by light intensity and the irradiation time [63]. In addition, some tissue adhesives are crosslinked through a combination of multiple crosslinking strategies, such as the combination of ionic and covalent crosslinking [63], Schiff base and coordination crosslinking [15], and Schiff-base crosslinking and ionic crosslinking [64]. A multiply crosslinked tissue adhesive can show the advantages of each crosslinking type, and due to an increase in crosslinking density, the resultant tissue adhesive usually exhibits a better cohesive strength than singly crosslinked adhesives [15,64].…”