Physicochemical modulation of chitosan‐based hydrogels induces different biological responses: Interest for tissue engineering

Abstract

Polysaccharide-based hydrogels are remarkable materials for the development of tissue engineering strategies as they meet several critical requirements for such applications and they may partly mimic the extracellular matrix. Chitosan is widely envisioned as hydrogel in biomedical fields for its bioresorbability, biocompatibility, and fungistatic and bacteriostatic properties. In this study, we report that the modulation of the polymer concentration, the degree of acetylation, the gelation processes [or neutralization routes (NR)] in the preparation of different chitosan-based hydrogels lead to substantially and significantly different biological responses. We show that it is possible to tune the physicochemical characteristics, mechanical properties, and biological responses of such matrices. Physical hydrogels prepared from highly acetylated chitosan were softer, degraded quickly in vivo, and were not suitable for in vitro culture of human mesenchymal stem and progenitor derived endothelial cells. In contrast, for a same chitosan concentration and obtained by the same processing route, a low degree of acetylation chitosan hydrogel provided a more elastic material, better cell adhesion on its surface and tissue regeneration, and restored tissue neo-vascularization as well. This work offers promising and innovative perspectives for the design of hydrogel materials with tunable properties for tissue engineering and regenerative medicine.

Chitosan: Gels and Interfacial Properties

“…Depending on the nature of the solvent and the chitosan's fraction of acetylated units, different gel morphologies can be obtained with different biological response. In a study by Rami et al, it was shown that soft and easily degraded gels manufactured from a highly acetylated chitosan were not suitable for culture of human mesenchymal stem cells, whereas a highly deacetylated chitosan following the same processing route gave rise to more solid gels with improved cell adhesion ( Figure 3) [22].…”

“…Chitosan based hydrogels are of interest in tissue engineering applications, as they have good biocompatibility, are biodegradable in vivo, are low-toxic and non-immunogenic, and have tunable gel properties [39]. Additionally, and rather uniquely, chitosan gels are cationic and are able to interact with structural molecules such as glycosaminoglycans and glycoproteins present in the extracellular matrix [22,39], or indeed with other anionic biopolymers to form mixed biopolymer scaffolds to optimize either the mechanical or biological properties of the biomaterial [40]. Most chitosan scaffolds for tissue engineering are of this mixed type [10].…”

“…Manufacturing process to obtain chitosan aqueous hydrogels and hydro-alcoholic hydrogel and photographs of the resulting gel products (scale bar = 5 mm). Reprinted with permission from American Chemical Society 2014 [22].…”

“…Biopolymer hydrogels are an obvious choice for the scaffolding material as they provide the necessary aqueous environment for cell growth, and are able to provide mechanical properties similar to native tissues [10,22]. Chitosan based hydrogels are of interest in tissue engineering applications, as they have good biocompatibility, are biodegradable in vivo, are low-toxic and non-immunogenic, and have tunable gel properties [39].…”

Ingénierie tissulaire

“…Le chitosane est ainsi largement utilisé comme hydrogel dans le domaine biomédical pour sa biorésorbabi-lité, sa biocompatibilité et son pouvoir bactériosta-tique. Les paramètres comme la masse molaire, la concentration en polymère, le degré d'acétylation, le processus de gélification dans la préparation de différents hydrogels à base de chitosane, conduisent à des réponses biologiques différentes [24]. Les hydrogels physiques préparés à partir de chitosane hautement acétylés sont en effet dégradés rapidement in vivo, et ne conviennent pas à la culture in vitro de cellules souches mésenchymateuses humaines ou de cellules endothéliales dérivées de leurs progéniteurs circulants [25].…”