Novel thermosensitive chitosan hydrogels: in vivo evaluation

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Chitosan is a biocompatible and biodegradable polymer with pharmaceutical potential.
• Thermosensitive hydrogels offer advantages like injectability and in situ gelation.
• Trehalose, a polysaccharide, can act as a gel-inducer and lyoprotectant.

Purpose of the Study:

• To develop and characterize novel thermosensitive chitosan-based hydrogels.
• To evaluate the injectability, in situ formation, and long-term stability of these hydrogels.
• To assess the in vivo biocompatibility and degradation profile of the hydrogel implants.

Main Methods:

• Homogeneous reacetylation of chitosan to a deacetylation degree of ~50%.
• Formulation of thermosensitive hydrogels with trehalose.
• Lyophilization and rehydration studies to assess stability.
• Rheological characterization to determine mechanical properties.
• In vivo studies in Sprague-Dawley rats for implant formation and permanence.
• Histopathological analysis of implant sites.

Main Results:

• The developed chitosan-trehalose hydrogels exhibited thermosensitive sol-gel transition.
• Lyophilization and rehydration did not compromise the thermosensitive behavior, enabling long-term storage.
• Increasing chitosan concentration from 1.4% to 2.2% (w/w) increased storage moduli.
• In vivo evaluation confirmed in situ implant formation and permanence up to 3 months.
• Histopathology revealed a mild, transient inflammatory response with complete gel absorption.

Conclusions:

• Thermosensitive chitosan-trehalose hydrogels are suitable for long-term storage and clinical use.
• These injectable, in situ forming hydrogels demonstrate excellent biocompatibility and biodegradability.
• The developed hydrogels show significant promise for applications in drug delivery and tissue engineering.