Electro and magnetoactive printed bi-functional actuators based on alginate hybrid hydrogels.

Soft materials are attracting much attention for the development of biostructures able to mimic the movement of natural systems by remote actuation. Multi-sensitive hydrogels are among the best materials for obtaining dynamic and biocompatible soft structures for soft actuators and related biomedical devices. Nevertheless, bioinks based on naturally occurring and stimuli responsive hydrogels able to be 3D printed continues being a challenge for advanced applications. In this work 3D printable electrically and magnetically responsive, non-cytotoxic, hybrid hydrogels based on alginate and zero monovalent iron nanoparticles (NPs) are presented. The effect of NPs addition on the physico-chemical properties of the hydrogels is addressed, together with its effect on the functional electroactive and magnetoactive response. NPs concentration up to 10 % do not affect the mechanical stability of the gels, while promoting an increase actuation response.

Dynamic and Self-Healable Chitosan/Hyaluronic Acid-Based In Situ-Forming Hydrogels.

In situ-forming, biodegradable, and self-healing hydrogels, which maintain their integrity after damage, owing to dynamic interactions, are essential biomaterials for bioapplications, such as tissue engineering and drug delivery. This work aims to develop in situ, biodegradable and self-healable hydrogels based on dynamic covalent bonds between N-succinyl chitosan (S-CHI) and oxidized aldehyde hyaluronic acid (A-HA). A robust effect of the molar ratio of both S-CHI and A-HA was observed on the swelling, mechanical stability, rheological properties and biodegradation kinetics of these hydrogels, being the stoichiometric ratio that which leads to the lowest swelling factor (×12), highest compression modulus (1.1·10−3 MPa), and slowest degradation (9 days). Besides, a rapid (3 s) self-repairing ability was demonstrated in the macro scale as well as by rheology and mechanical tests. Finally, the potential of these biomaterials was evidenced by cytotoxicity essay (>85%).

Photocrosslinkable and self-healable hydrogels of chitosan and hyaluronic acid.

Biocompatible and biodegradable hydrogels with biomimetic properties, such as self-repairing, are increasingly interesting for biomedical applications, particularly when they can be printed or in situ formed to mimic extracellular matrix or as personalized implantable devices in tissue regeneration or drug delivery. Photocrosslinkable hydrogels based on methacrylated chitosan (CHIMe) and hyaluronic acid that exhibit according with their composition, tuneable physico-chemical properties are here presented. The study of the conversion, gelation time, mechanical and rheological properties of photopolymerized CHIMe showed an optimal phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) initiator feed (0.1 % w). These photocrosslinkable hydrogels demonstrated being able to promote doubly crosslinked hydrogels with similar Young Moduli regardless the cycles of self-healing processes, and tailored swelling (25-70 swelling factor), mechanical (1 × 10-4-2 × 10-2 MPa) and rheological properties, as a function of polysaccharides relative content. Clear evidences have been found that fast photopolymerization of CHIMe/HA solutions leads to biocompatible (>80 % cell viability), biodegradable (20-24 days in hydrolytic medium) and robust self-healable hydrogels suitable for advanced biomedical and tissue engineering applications.

pH-Induced 3D Printable Chitosan Hydrogels for Soft Actuation.

Three-dimensional (3D) printing represents a suitable technology for the development of biomimetic scaffolds for biomedical and tissue engineering applications. However, hydrogel-based inks' printability remains a challenge due to their restricted print accuracy, mechanical properties, swelling or even cytotoxicity. Chitosan is a natural-derived polysaccharide that has arisen as a promising bioink due to its biodegradability, biocompatibility, sustainability and antibacterial properties, among others, as well as its ability to form hydrogels under the influence of a wide variety of mechanisms (thermal, ionic, pH, covalent, etc.). Its poor solubility at physiological pH, which has traditionally restricted its use, represents, on the contrary, the simplest way to induce chitosan gelation. Accordingly, herein a NaOH strong base was employed as gelling media for the direct 3D printing of chitosan structures. The obtained hydrogels were characterized in terms of morphology, chemical interactions, swelling and mechanical and rheological properties in order to evaluate the influence of the gelling solution's ionic strength on the hydrogel characteristics. Further, the influence of printing parameters, such as extrusion speed (300, 600 and 800 mm/min) and pressure (20-35 kPa) and the cytocompatibility were also analyzed. In addition, printed gels show an electro-induced motion due to their polycationic nature, which highlights their potential as soft actuators and active scaffolds.

3D printable self-healing hyaluronic acid/chitosan polycomplex hydrogels with drug release capability.

Multifunctional printable biomaterials are at the base of advanced biomedical applications. Chitosan (CHI) and hyaluronic acid (HA) allow the development of polycomplex hydrogels with tailorable properties, including self-healing and controlled drug release. This work correlates and optimizes the mucoadhesive, swelling, biodegradation, mechanical and rheological properties of HA/CHI polycomplex hydrogels with synthesis parameters such as polysaccharide content and complexation time, according to the interaction forces established between both polyelectrolytes. Related to these dynamic forces, the self-healing ability of the hydrogels was investigated together with the potential of the HA/CHI polycomplex hydrogels for 3D printing. Finally, their capability to modulate and promote controlled release of a variety of drugs (anionic and anti-inflammatory sodium diclofenac and the neutral antibiotic rifampicin) was demonstrated. Thus, the reported tunable properties, self-repair ability, printability and drug release properties, demonstrate the suitability of HA/CHI hydrogels for advanced biomedical applications.

Polysaccharide-Based In Situ Self-Healing Hydrogels for Tissue Engineering Applications.

In situ hydrogels have attracted increasing interest in recent years due to the need to develop effective and practical implantable platforms. Traditional hydrogels require surgical interventions to be implanted and are far from providing personalized medicine applications. However, in situ hydrogels offer a wide variety of advantages, such as a non-invasive nature due to their localized action or the ability to perfectly adapt to the place to be replaced regardless the size, shape or irregularities. In recent years, research has particularly focused on in situ hydrogels based on natural polysaccharides due to their promising properties such as biocompatibility, biodegradability and their ability to self-repair. This last property inspired in nature gives them the possibility of maintaining their integrity even after damage, owing to specific physical interactions or dynamic covalent bonds that provide reversible linkages. In this review, the different self-healing mechanisms, as well as the latest research on in situ self-healing hydrogels, is presented, together with the potential applications of these materials in tissue regeneration.

ß-Glycerol phosphate/genipin chitosan hydrogels: A comparative study of their properties and diclofenac delivery.

Thermosensitive hydrogels based on polysaccharides are suitable candidates for the design of biodegradable and biocompatible injectable drug delivery systems. Thus, the combination of chitosan (CHI) and ß-glycerol phosphate disodium salt (ß-GP) has been intensively investigated to develop thermo-induced physical gels. With the aim of exploring the possibilities of optimization of these hydrogels, in this work, chitosan, ß-GP and naturally extracted crosslinking agent, genipin (GEN), have been successfully combined, obtaining co-crosslinked hydrogels with both in situ physical and covalent crosslinking. A wide range of ß-GP concentrations have been selected in order to analyze its influence on a variety of properties, including gelation time, pore size, water uptake ability, in vitro hydrolytic and enzymatic degradation, mucoadhesion and mechanical and rheological properties. Furthermore, the potential application of the developed systems for the administration and controlled release of an anti-inflammatory anionic drug, such as diclofenac, has been successfully demonstrated.

Synthesis and Characterization of Covalently Crosslinked pH-Responsive Hyaluronic Acid Nanogels: Effect of Synthesis Parameters.

Stable hyaluronic acid nanogels were obtained following the water-in-oil microemulsion method by covalent crosslinking with three biocompatible crosslinking agents: Divinyl sulfone, 1,4-butanediol diglycidyl ether (BDDE), and poly(ethylene glycol) bis(amine). All nanoparticles showed a pH-sensitive swelling behavior, according to the pKa value of hyaluronic acid, as a consequence of the ionization of the carboxylic moieties, as it was corroborated by zeta potential measurements. QELS studies were carried out to study the influence of the chemical structure of the crosslinking agents on the particle size of the obtained nanogels. In addition, the effect of the molecular weight of the biopolymer and the degree of crosslinking on the nanogels dimensions was also evaluated for BDDE crosslinked nanoparticles, which showed the highest pH-responsive response.