Stability and catechol modification of chitosan hydrogels for cell therapy

Abstract

Injectable hydrogels based on chitosan (CH), a polysaccharide biopolymer that is soluble in acidic conditions, are increasingly used for biomedical and pharmaceutical applications. To achieve the prospective applications, low viscosity before and during injection, rapid gelation, high mechanical properties, tissue-adhesion and biodegradation are required. In order to be used for cell therapy, excellent cytocompatibility is also mandatory. Merging all required properties in one formulation is still an issue as of today. The recently designed thermosensitive CH hydrogels at Laboratory of Endovascular Biomaterials (LBeV) by using novel gelling agents, exhibit strong mechanical properties, cytocompatibility and tunable gelation time. For possible clinical transfer, the stability of the CH and gelling agent solutions is of great importance. The first objective of this master research is to study the stability of chitosan solution, gelling agents, and chitosan hydrogel over time under different storage conditions, to define how long and in which condition the storage of chitosan and gelling agents is possible while they keep their rheological properties and gelation kinetic. The results showed that CH solution and gelling agents that stored at low temperature (4- 5°C) had less changes in comparison to those stored at room temperature. In a second step, in order to improve the adhesive properties of the gel, the chitosan was modified by covalent grafting of catechol groups and the properties of the obtained hydrogel were characterized by studying, in particular, the impact of the addition of hydrogen chloride (HCl) in the solution of chitosan. The grafting protocol of catechol has been improved to avoid oxidation during manufacture and we have shown that hydrogels gelling at human body temperature can be formed by this method. The concentration of HCl tends to improve the adhesive properties, but to reduce the strength of the hydrogels and gelation kinetic. This study is a significant first step towards the development of a thermosensitive, cohesive and adhesive hydrogel. The next steps will be to optimize the hydrogels, to improve the understanding of the chemical mechanisms involved, and to evaluate their potential for cellular encapsulation.

Date	28 Mar 2018
Original language	American English
Awarding Institution	École de technologie supérieure
Supervisor	Sophie Lerouge (Supervisor) & Marta Cerruti (Co-supervisor)