Abstract: [Abstract] Objective  To prepare temperature-responsive chitosan gel combined with drug-loaded chitosan microspheres（T-responsive CG/CMS），and to investigate its controlled-release effect to provide a reference for the load of exogenous growth factors used in periodontal tissue regeneration. Methods  The bovine serum albumin (BSA) was used as the model drug. The BSA-loaded microspheres were prepared using ionic gelation method. The surface morphology was observed by scanning electron microscopy. The drug loading and encapsulation efficiency were determined. Then the BSA-loaded microspheres were mixed in chitosan/β-glycerophosphate system to form T-responsive CG/CMS-BSA. The sustained-release effect of bovine serum albumin was detected by ultraviolet sepectrophotometry. Results  The good shape and uniform particle size citosan microsphere（CSM）was generated when chitosan concentration was between 0.6 g/L and 2.0 g/L, tripolyphosphate concentration was between 0.5 g/L and 1.0 g/L. With optimizing the formulation of T-responsive CG/CMS, its transition from sol to gel occurred at 37 ℃, showing the temperature sensitivity. The release in vitro tests showed that the BSA release rate of the T-responsive CG/CMS slowed down, and the 24 h cumulative release rate was only 16%, while the 24 h cumulative release rate of the unmingled temperature-responsive chitosan gel was up to 70%. Conclusion  T-responsive CG/CMS showed the potential for sustained release of protein-based drugs, and thus it could be used in periodontal tissue engineering to accomplish the goal of sustained release of the growth factors..

Key words: Chitosan microspheres, Temperature-responsive chitosan gel, Drug delivery, Periodontal tissue engineering