Nowadays, there are still numerous challenges for well-known biomedical applications, such as tissue engineering (TE), wound healing and controlled drug delivery, which must be faced and solved. Hydrogels have been proposed as excellent candidates for these applications, as they have promising properties for the mentioned applications, including biocompatibility, biodegradability, great absorption capacity and tunable mechanical properties. However, depending on the material or the manufacturing method, the resulting hydrogel may not be up to the specific task for which it is designed, thus there are different approaches proposed to enhance hydrogel performance for the requirements of the application in question. The main purpose of this review article was to summarize the most recent trends of hydrogel technology, going through the most used polymeric materials and the most popular hydrogel synthesis methods in recent years, including different strategies of enhancing hydrogels’ properties, such as cross-linking and the manufacture of composite hydrogels. In addition, the secondary objective of this review was to briefly discuss other novel applications of hydrogels that have been proposed in the past few years which have drawn a lot of attention.

Hydrogels are considered good biomaterials for soft tissue regeneration. In this sense, collagen is the most used raw material to develop hydrogels, due to its high biocompatibility. However, its low mechanical resistance, thermal stability and pH instability have generated the need to look for alternatives to its use. In this sense, the combination of collagen with another raw material (i.e., polysaccharides) can improve the final properties of hydrogels. For this reason, the main objective of this work was the development of hydrogels based on collagen and chitosan. The mechanical, thermal and microstructural properties of the hydrogels formed with different ratios of collagen/chitosan (100/0, 75/25, 50/50, 25/75 and 0/100) were evaluated after being processed by two variants of a protocol consisting in two stages: a pH change towards pH 7 and a temperature drop towards 4 °C. The main results showed that depending on the protocol, the physicochemical and microstructural properties of the hybrid hydrogels were similar to the unitary system depending on the stage carried out in first place, obtaining FTIR peaks with similar intensity or a more porous structure when chitosan was first gelled, instead of collagen. As a conclusion, the synergy between collagen and chitosan improved the properties of the hydrogels, showing good thermomechanical properties and cell viability to be used as potential biomaterials for Tissue Engineering.

Tissue engineering (TE) demands scaffolds that have the necessary resistance to withstand the mechanical stresses once implanted in our body, as well as excellent biocompatibility. Hydrogels are postulated as interesting materials for this purpose, especially those made from biopolymers. In this study, the microstructure and rheological performance, as well as functional and biological properties of chitosan and collagen hydrogels (CH/CG) crosslinked with different coupling agents, both natural such as d-Fructose (F), genipin (G) and transglutaminase (T) and synthetic, using a combination of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride with N-hydroxysuccinimide (EDC/NHS) will be assessed. FTIR tests were carried out to determine if the proposed crosslinking reactions for each crosslinking agent occurred as expected, obtaining positive results in this aspect. Regarding the characterization of the properties of each system, two main trends were observed, from which it could be established that crosslinking with G and EDC-NHS turned out to be more effective and beneficial than with the other two crosslinking agents, producing significant improvements with respect to the base CH/CG hydrogel. In addition, in vitro tests demonstrated the potential application in TE of these systems, especially for those crosslinked with G, T and EDC-NHS.

The regeneration of soft tissues that connect, support or surround other tissues is of great interest. In this sense, hydrogels have great potential as scaffolds for their regeneration. Among the different raw materials, chitosan stands out for being highly biocompatible, which, together with its biodegradability and structure, makes it a great alternative for the manufacture of hydrogels. Therefore, the aim of this work was to develop and characterize chitosan hydrogels. To this end, the most important parameters of their processing, i.e., agitation time, pH, gelation temperature and concentration of the biopolymer used were rheologically evaluated. The results show that the agitation time does not have a significant influence on hydrogels, whereas a change in pH (from 3.2 to 7) is a key factor for their formation. Furthermore, a low gelation temperature (4 °C) favors the formation of the hydrogel, showing better mechanical properties. Finally, there is a percentage of biopolymer saturation, from which the properties of the hydrogels are not further improved (1.5 wt.%). This work addresses the development of hydrogels with high thermal resistance, which allows their use as scaffolds without damaging their mechanical properties.

In the last few years, electrospinning has proved to be one of the best methods for obtaining membranes of a micro and nanometric fiber size. This method mainly consists in the spinning of a polymeric or biopolymeric solution in solvents, promoted by the difference in the electric field between the needle and collector, which is finally deposited as a conjunction of randomly oriented fibers. The present work focuses on using cellulose derivatives (namely cellulose acetate and ethylcellulose), based on the revaluation of these byproducts and waste products of biorefinery, to produce nanostructured nanofiber through electrospinning with the objective of establishing a relation between the initial solutions and the nanostructures obtained. In this sense, a complete characterization of the biopolymeric solutions (physicochemical and rheological properties) and the resulting nanostructures (microstructural and thermal properties) was carried out. Therefore, solutions with different concentrations (5, 10, 15, and 20 wt%) of the two cellulose derivatives and different solvents with several proportions between them were used to establish their influence on the properties of the resulting nanostructures. The results show that the solutions with 10 wt% in acetic acid/H₂O and 15 wt% in acetone/N,N-dimethylformamide of cellulose acetate and 5 wt% of ethylcellulose in acetone/N,N-dimethylformamide, exhibited the best properties, both in the solution and nanostructure state.

An increase in resistance to key antibiotics has made the need for novel treatments for the gastric colonization of Helicobacter pylori (H. pylori) a matter of the utmost urgency. Recent studies tackling this topic have focused either on the discovery of new compounds to ameliorate therapeutic regimes (such as vonoprazan) or the synthesis of gastroretentive drug delivery systems (GRDDSs) to improve the pharmacokinetics of oral formulations. The use of semi-interpenetrating polymer networks (semi-IPNs) that can act as super-porous hydrogels for this purpose is proposed in the present work, specifically those displaying low ecological footprint, easy synthesis, self-floating properties, high encapsulation efficiency for drugs such as amoxicillin (AMOX), great mucoadhesiveness, and optimal mechanical strength when exposed to stomach-like fluids. To achieve such systems, biodegradable synthetic copolymers containing acid-labile monomers were prepared and interpenetrated with guar gum (GG) in a one-pot polymerization process based on thiol-ene click reactions. The resulting matrices were characterized by SEM, GPC, TGA, NMR, and rheology studies, and the acidic hydrolysis of the acid-sensitive polymers was also studied. Results confirm that some of the obtained matrices are expected to perform optimally as GRDDSs for the sustained release of active pharmaceutical ingredients at the gastrointestinal level, being a priori facilitated by its disaggregation. Therefore, the optimal performance of these systems is assessed by varying the molar ratio of the labile monomer in the matrices.