Biological Analysis of Simvastatin-releasing Chitosan Scaffold as a Cell-free System for Pulp-dentin Regeneration

Author(s)

Soares, Diana G. ^[1] ; Anovazzi, Giovanna ^[2] ; Bordini, Ester Alves F. ^[3] ; Zuta, Uxua O. ^[3] ; Silva Leite, Maria Luisa A. ^[3] ; Basso, Fernanda G. ^[3] ; Hebling, Josimeri ^[2] ; de Souza Costa, Carlos A. ^[3]

Affiliation

^[1] Univ Sao Paulo, Baum Sch Dent, Dept Operat Dent Endondont & Dent Mat, Sao Paulo - Brazil

^[2] Univ Estadual Paulista, UNESP, Dept Orthodont & Pediat Dent, Araraquara Sch Dent, Sao Paulo - Brazil

^[3] Univ Estadual Paulista, UNESP, Dept Physiol & Pathol, Araraquara Sch Dent, Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF ENDODONTICS; v. 44, n. 6, p. 971-976, JUN 2018.
• Web of Science Citations: 2

Abstract

Introduction: The improvement of biomaterials capable of driving the regeneration of the pulp-dentin complex mediated by resident cells is the goal of regenerative dentistry. In the present investigation, a chitosan scaffold (CHSC) that released bioactive concentrations of simvastatin (SIM) was tested, aimed at the development of a cell-free tissue engineering system. Methods: First, we performed a dose-response assay to select the bioactive dose of SIM capable of inducing an odontoblastic phenotype in dental pulp cells (DPCs); after which we evaluated the synergistic effect of this dosage with the CHSC/DPC construct. SIM at 1.0 mu mol/L (CHSC-SIM1.0) and 0.5 mu mol/L were incorporated into the CHSC, and cell viability, adhesion, and calcium deposition were evaluated. Finally, we assessed the biomaterials in an artificial pulp chamber/3-dimensional culture model to simulate the cell-free approach in vitro. Results: SIM at 0.1 Amol/L was selected as the bioactive dose. This drug was capable of strongly inducing an odontoblastic phenotype on the DPC/CHSC construct. The incorporation of SIM into CHSC had no deleterious effect on cell viability and adhesion to the scaffold structure. CHSC-SIM1.0 led to significantly higher calcium-rich matrix deposition on scaffold/dentin disc assay compared with the control (CHSC). This biomaterial induced the migration of DPCs from a 3-dimensional culture to its surface as well as stimulated significantly higher expressions of alkaline phosphatase, collagen type 1 alpha 1, dentin matrix acidic phosphoprotein 1, and dentin sialophosphoprotein on 3-dimensional cultured DPCs than on those in contact with CHSC. Conclusions: CHSC-SIM1.0 scaffold was capable of increasing the chemotaxis and regenerative potential of DPCs. (AU)

• FAPESP's process: 13/23520-0 - Bioactivity of experimental scaffolds of chitosan and collagen on cultured human dental pulp cells
• Grantee: Diana Gabriela Soares dos Passos
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/15674-5 - Association of tissue engineering techniques for mineralized tissue regeneration under degenerative inflammatory stimulus: analysis on 3D-culture perfusion bioreactor and animal inflammatory models
• Grantee: Diana Gabriela Soares dos Passos
• Support Opportunities: Research Grants - Young Investigators Grants