Diana G Soares1, Giovanna Anovazzi2, Ester Alves F Bordini3, Uxua O Zuta3, Maria Luísa A Silva Leite3, Fernanda G Basso3, Josimeri Hebling2, Carlos A de Souza Costa4. 1. Department of Operative Dentistry, Endondontics and Dental Materials, Bauru School of Dentistry, University of São Paulo-USP, São Paulo, Brazil. 2. Department of Orthodontics and Pediatric Dentistry, Araraquara School of Dentistry, Universidade Estadual Paulista-UNESP, São Paulo, Brazil. 3. Department of Physiology and Pathology, Araraquara School of Dentistry, Universidade Estadual Paulista-UNESP, São Paulo, Brazil. 4. Department of Physiology and Pathology, Araraquara School of Dentistry, Universidade Estadual Paulista-UNESP, São Paulo, Brazil. Electronic address: casouzac@foar.unesp.br.
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 μmol/L (CHSC-SIM1.0) and 0.5 μmol/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 μmol/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.
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 μmol/L (CHSC-SIM1.0) and 0.5 μmol/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 μmol/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.
Authors: Bruna de Siqueira Nunes; Rosana Araújo Rosendo; Abrahão Alves de Oliveira Filho; Marcus Vinícius Lia Fook; Wladymyr Jefferson Bacalhau de Sousa; Rossemberg Cardoso Barbosa; Hermano de Vasconcelos Pina; João Emídio da Silva Neto; Solomon Kweku Sagoe Amoah; Carlos Eduardo Fontana; Carlos Eduardo da Silveira Bueno; Alexandre Sigrist De Martin Journal: Materials (Basel) Date: 2021-01-20 Impact factor: 3.623