New Smart Bioactive and Biomimetic Chitosan-Based Hydrogels for Wounds Care Management

Abstract

Wound management represents a continuous challenge for health systems worldwide, considering the growing incidence of wound-related comorbidities, such as diabetes, high blood pressure, obesity, and autoimmune diseases. In this context, hydrogels are considered viable options since they mimic the skin structure and promote autolysis and growth factor synthesis. Unfortunately, hydrogels are associated with several drawbacks, such as low mechanical strength and the potential toxicity of byproducts released after crosslinking reactions. To overcome these aspects, in this study new smart chitosan (CS)-based hydrogels were developed, using oxidized chitosan (oxCS) and hyaluronic acid (oxHA) as nontoxic crosslinkers. Three active product ingredients (APIs) (fusidic acid, allantoin, and coenzyme Q10), with proven biological effects, were considered for inclusion in the 3D polymer matrix. Therefore, six API-CS-oxCS/oxHA hydrogels were obtained. The presence of dynamic imino bonds in the hydrogels’ structure, which supports their self-healing and self-adapting properties, was confirmed by spectral methods. The hydrogels were characterized by SEM, swelling degree, pH, and the internal organization of the 3D matrix was studied by rheological behavior. Moreover, the cytotoxicity degree and the antimicrobial effects were also investigated. In conclusion, the developed API-CS-oxCS/oxHA hydrogels have real potential as smart materials in wound management, based on their self-healing and self-adapting properties, as well as on the benefits of APIs.

Biomedical Trends in Stimuli-Responsive Hydrogels with Emphasis on Chitosan-Based Formulations

“…Except for FA-CS-oxHA, which exhibited some level of toxicity at higher concentrations, hydrogels were non-toxic; FA-CS-oxHA exhibited anti-bacterial effects against Staphylococcus aureus. Overall, the study indicated that non-toxic smart hydrogels with oxidized polymers as cross-linkers are useful for treating irregular deep wounds due to their self-healing and adapting properties [150].…”

Transforming Wound Management: Nanomaterials and Their Clinical Impact

“…Chitosan is a natural biodegradable polysaccharide derived from chitin deacetylation. It has the same glycosaminoglycan component as ECM, apart from the ability to be biocompatible, biodegradable; it also has hemostatic, antibacterial and antifungal properties which is unique to chitosan [ 51 , 52 ]. This advantage provides faster diabetic foot ulcer recovery.…”

“…Collagen is a vital constituent present in ECM. Collagen stimulates fibroblast migration in the damaged tissue and modulates the granulation process, helping in cell attachment and proliferation [ 51 ]. However, it is commonly combined with synthetic polymers because it is unstable at higher temperatures [ 54 ].…”

Modern Approaches in Wounds Management

“…CS/oxidized konjac glucomannan Silver (nanoparticles) Self-healing, self-adapting [71] Oxidized CS/bacterial cellulose -Self-healing [158] N,O-carboxymethyl CS/oxidized dextran -Self-healing, injectability [159] Quaternized CS/oxidized dextran Tobramycin Self-healing [160] Carboxymethyl CS/oxidized quaternized guaran -Self-healing [122] CS/oxidized CS Fusidic acid, alantoin, coenzyme Q10 Self-healing, self-adapting [161] CS/polyvinylpyrrolidone/alginate/ poly(ε-caprolactone) -Thermo-responsive [162] CS/poly(aspartic acid) Amoxicilin pH/thermo-responsive [163] Alginate is an anionic natural copolymer, composed of blocks of guluronate and mannuronate, obtained by alkaline extraction from brown algaes (Laminaria spp., Ascophyllumnodosum, Macrocysti spyrifera) or by microbial synthesis (Azotobacter, Pseudomonas). It is characterized by several properties, such as biocompatibility, low toxicity, economical affordable, and ease of gelation, which makes alginate attractive for biomedical applications such as tissue engineering, drug delivery, biosensing, and wound healing [164,165].…”