Caractérisation et optimisation d'hydrogels de chitosane bioactifs et injectables pour applications biomédicales

Abstract

Postoperative adhesions are a complication that occurs after nearly 97% of abdominal surgeries and can cause intestinal obstructions and chronic pain. Strategies to prevent them are divided into three categories: pharmacological agents, which are often ineffective, physical barriers that are non-injectable and difficult to handle, and fluid barriers that have weak mechanical properties and a degradation kinetic that is often not appropriate. Thermosensitive chitosan hydrogels with strong mechanical properties have been recently developed thanks to a combination of gelling agents. These gels are liquid at room temperature and can rapidly gel at 37°C. The first objective of this study is to determine the best formulation of chitosan hydrogel to prevent adhesions and evaluate its potential in vivo in a rat model by comparing its efficacy with a commercialized physical barrier, Interceed®. The results showed that the incidence of adhesions was statistically reduced thanks to the administration of the chitosan gel but this treatment was less effective than Interceed®. However, Interceed® cannot be used in minimally invasive surgery because it is not injectable. The effectiveness of our hydrogel may have been limited by its slow degradation kinetics but an optimization of the DDA of chitosan could make these results even more promising. Secondly, the potential of chitosan hydrogels for the regeneration of cartilage was evaluated by comparing their physico-chemical, rheological and mechanical properties with those of a commercialized product, JointRep ™ (OligoMedic Inc.). One of the most critical aspects of tissue engineering is to develop biomaterials capable of supporting cell growth. Collagen is the most abundant component of the extracellular matrix and is a substrate for cells. The third objective of this project is to evaluate the mechanical and biological properties of chitosan/collagen hydrogels for tissue engineering. After Live/Dead assays, the addition of collagen seemed to improve cell survival and proliferation, however an optimization of chitosan/collagen hydrogels would be necessary in order to combine good cytocompatibility and mechanical properties.

Date	28 Aug 2017
Original language	French
Awarding Institution	École de technologie supérieure
Supervisor	Sophie Lerouge (Supervisor)