Craig Bellamy1, Suja Shrestha1, Calvin Torneck1, Anil Kishen2. 1. Discipline of Endodontics, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada. 2. Discipline of Endodontics, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada. Electronic address: akishen@gmail.com.
Abstract
INTRODUCTION: This 2-part study hypothesized that a bioactive scaffold containing a sustained transforming growth factor (TGF)-β1-releasing nanoparticle system will promote migration and enhance differentiation of stem cells from the apical papilla (SCAP). The study aimed to develop and characterize a novel modified chitosan-based scaffold containing TGF-β1-releasing chitosan nanoparticles (TGF-β1-CSnp) to enhance migration and differentiation of SCAP. METHODS: Part I concerns the synthesis and characterization of a carboxymethyl chitosan-based scaffold and TGF-β1-CSnp. Part II examines the effect of sustained TGF-β1 release from scaffold containing TGF-β1-CSnp on odontogenic differentiation of SCAP. RESULTS: The scaffold demonstrated properties conducive to cellular activities. The incorporation of TGF-β1 in CSnp allowed sustained release of TGF-β1, facilitating delivery of a critical concentration of TGF-β1 at the opportune time. TGF-β1 bioactivity was maintained for up to 4 weeks. SCAP showed greater viability, migration, and biomineralization in the presence of TGF-β1-CSnp than in the presence of free TGF-β1. SCAP cultured in TGF-β1-CSnp + scaffold showed significantly higher dentin matrix protein-1 and dentin sialophosphoprotein signals compared with free TGF-β1 + scaffold or CSnp + scaffold. CONCLUSIONS: These experiments highlighted the potential of a carboxymethyl chitosan-based scaffold with growth factor releasing nanoparticles to promote migration and differentiation of SCAP. The results of this study may have direct application to improve current endodontic regenerative protocols.
INTRODUCTION: This 2-part study hypothesized that a bioactive scaffold containing a sustained transforming growth factor (TGF)-β1-releasing nanoparticle system will promote migration and enhance differentiation of stem cells from the apical papilla (SCAP). The study aimed to develop and characterize a novel modified chitosan-based scaffold containing TGF-β1-releasing chitosan nanoparticles (TGF-β1-CSnp) to enhance migration and differentiation of SCAP. METHODS: Part I concerns the synthesis and characterization of a carboxymethyl chitosan-based scaffold and TGF-β1-CSnp. Part II examines the effect of sustained TGF-β1 release from scaffold containing TGF-β1-CSnp on odontogenic differentiation of SCAP. RESULTS: The scaffold demonstrated properties conducive to cellular activities. The incorporation of TGF-β1 in CSnp allowed sustained release of TGF-β1, facilitating delivery of a critical concentration of TGF-β1 at the opportune time. TGF-β1 bioactivity was maintained for up to 4 weeks. SCAP showed greater viability, migration, and biomineralization in the presence of TGF-β1-CSnp than in the presence of free TGF-β1. SCAP cultured in TGF-β1-CSnp + scaffold showed significantly higher dentin matrix protein-1 and dentin sialophosphoprotein signals compared with free TGF-β1 + scaffold or CSnp + scaffold. CONCLUSIONS: These experiments highlighted the potential of a carboxymethyl chitosan-based scaffold with growth factor releasing nanoparticles to promote migration and differentiation of SCAP. The results of this study may have direct application to improve current endodontic regenerative protocols.