Development of macro-porous chitosan-calcium scaffolds with controlled release of simvastatin: evaluation of the regenerative potential at inflamed areas

Abstract

The regeneration of mineralized tissues under degenerative inflammatory stimulus presents a challenge situation, since the reparative potential of the resident stem cells may be negatively influenced in the presence of high dosage of pro-inflammatory mediators. In this research project, an association of tissue engineering techniques will be evaluated in order to develop chitosan scaffolds with an interconnected microporous network and contaninig calcium in its structure, capable to release simvastatin at specific dosages to modulate inflammation and tissue regeneration by resident cells, aiming the regeneration of bone and dentin. Initially, the anti-inflammatory and bioactive dosage of simvastatin will be selected for dental pulp (HDPC) and osteoblast (SAOS-2) cells from human origin, and the effect of these dosage associations on the regenerative potential will be evaluated under in vitro degenerative inflammatory stimulus (Phase 1). Thereafter, the technology for the development of a macroporous chitosan-calcium scaffold containing chitosan microspheres capable to promote the controlled release of previously selected simvastatin dosage will be stablished (Phase 2), and the bioactive effect of this material against HDPCs and SAOS-2 under degenerative inflamatory stimulus will be assessed (Phase 3). Finally, the biomaterial will be applied at specific sites in animals (Rattus novergiccus), using models of induction of chronic inflammatory lesion in bone and pulp tissue (Pahse 4). Data will be analysed statistically.