Simvastatin-Enriched Macro-Porous Chitosan-Calcium-Aluminate Scaffold for Mineralized Tissue Regeneration

Cassiano, Fernanda Balestrero; Soares, Diana Gabriela; Bordini, Ester Alves Ferreira; Anovazzi, Giovana; Hebling, Josimeri; Costa, Carlos Alberto de Souza

doi:10.1590/0103-6440202003252

Cited by 8 publications

(7 citation statements)

References 21 publications

(47 reference statements)

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“…The findings from the present study support further exploration of the use of resin‐modified glass ionomers and suggest the potential need to shift from calcium silicates to new alternatives, especially with the current developments in bioceramics and biological scaffolds (Cassiano et al, 2020; Hanna et al, 2020). The findings from the current study also support the idea that a one‐product‐fits‐all approach does not exist and further studies are needed to recommend specific bioceramic products to suit different clinical scenarios such as trauma versus caries or direct versus indirect pulp capping (Ali et al, 2021).…”

Section: Discussionsupporting

confidence: 71%

Effect of pulp capping materials on odontogenic differentiation of human dental pulp stem cells: An in vitro study

Bakr,

Shamel,

Raafat

et al. 2023

Clinical & Exp Dental Res

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ObjectivesMigration and differentiation of human dental pulp stem cells (hDPSCs) is a vital and key factor in the success of reparative dentin formation for maintenance of pulp vitality. Pulp capping materials are used to stimulate DPSCs to induce new dentin formation. Thus, the aim of the present study was to compare the response of DPSCs to four commercially available pulp capping materials: a bioactive bioceramic (Material 1), a nonresinous ready‐to‐use bioceramic cement (Material 2), a bioactive composite (Material 3), and a biocompatible, dual‐cured, resin‐modified calcium silicate (Material 4).Materials and MethodshDPSCs were isolated and cultured from freshly extracted teeth and were then characterized by flow cytometry and multilineage differentiation. Discs prepared from pulp capping materials were tested with hDPSCs and MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay, cell migration assay and odontogenic differentiation assay was performed. Expression of osteogenic markers (osteopontin, RUNX family transcription factor 2, osteocalcin) and the odontogenic marker (dentin sialophosphoprotein) was detected using reverse transcription‐polymerase chain reaction.ResultsMaterials 1, 2, and 3 generated more cell viability than Material 4. Furthermore, Material 4 showed the least wound exposure percentage, while Material 3 showed the highest percentage. Enhanced mineralization was found in hDSCPs cultured with Material 3, followed by Material 1, and then Material 2, while Material 4 revealed the least calcified mineralization.ConclusionsThe results of this study were inconclusive regards contemporary bioceramic materials designed for vital pulp therapy as they have different effects on hDPSC. Further testing for cytotoxicity using live‐dead staining, animal experiments, clinical trials, and independent analyses of these biomaterials is necessary for clinicians to make an informed decision for their use.

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Section: Discussionsupporting

confidence: 71%

Effect of pulp capping materials on odontogenic differentiation of human dental pulp stem cells: An in vitro study

Bakr,

Shamel,

Raafat

et al. 2023

Clinical & Exp Dental Res

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“…The released components of this composite biomaterial demonstrated improved cell proliferation and ALP activity, upregulating the mineralization by approximately four-fold compared to that displayed by the released components from single-component formulations. In our prior research on human pulp cells, the synergistic effect of bioactive mineral phases with low-dosage SV has been observed for chitosan-calcium hydroxide 4,5 and chitosancalcium aluminate formulations, 36 wherein an increase in odontoblastic markers was observed in the presence of adsorbed 1 µM SV, indicating a beneficial action of this association for the cell differentiation and deposition of the mineralized matrix. The incorporation of SV in CH-Ca scaffolds also has a chemotactic effect on human pulp cells.…”

Section: Discussionmentioning

confidence: 86%

Assessment of the regenerative potential of macro-porous chitosan-calcium simvastatin scaffolds on bone cells

et al. 2023

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This study evaluated the bioactive potential of a macro-porous chitosan scaffold incorporated with calcium hydroxide (CH-Ca) and functionalized with bioactive doses of simvastatin (SV) for bone tissue regeneration. Initially, the bioactive dose of SV in osteoblastic cells (SAOS-2) was determined. For the direct contact experiment, SAOS-2 cells were plated on scaffolds to assess cell viability and osteogenic differentiation. The second assay was performed at a distance using extracts from scaffolds incubated in culture medium to assess the effect of conditioned medium on viability and osteogenic differentiation. The initial screening showed that 1 μM SV presented the best biostimulating effects, and this dose was selected for incorporation into the CH-Ca and pure chitosan (CH) scaffolds. The cells remained viable throughout the direct contact experiment, with the greatest cell density in the CH-Ca and CH-Ca-SV scaffolds because of their higher porosity. The CH-Ca-SV scaffold showed the most intense bio-stimulating effect in assays in the presence and absence of osteogenic medium, leading to an increased deposition of mineralized matrix. There was an increase in the viability of cells exposed to the extracts for CH-Ca, CH-SV, and CH-Ca-SV during the one-day period. There was an increase in ALP activity in the CH-Ca and CH-Ca-SV; however, the CH-Ca-SV scaffold resulted in an intense increase in the deposition of mineralized nodules, approximately 56.4% at 7 days and 117% at 14 days, compared with CH (control). In conclusion, functionalization of the CH-Ca scaffold with SV promoted an increase in bioactivity, presenting a promising option for bone tissue regeneration.

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“…Chitosan (CH) and chitosan-calcium-hydroxide (CH-Ca) scaffolds were prepared by phase separation, following the technique previously established by our group (Soares et al 2020). Simvastatin (SV; ≥97% high-performance liquid chromatography, solid; Sigma-Aldrich) at 1 µM was incorporated by scaffold immersion and drying at 37°C, as proposed by Soares, Anovazzi, et al (2018) and Cassiano et al (2020). Refer to Appendix Figure 1 for details.…”

Section: Methodsmentioning

confidence: 99%

“…In our previous experiments, incorporation of 1 μM SV on chitosan and chitosan-calcium-aluminate scaffolds had better results than lower dosages, increasing alkaline phosphatase (ALP) activity and mineralized matrix deposition. This dosage also had a homing effect, by attracting human dental pulp cells from a 3-dimensional (3D) culture to scaffold surface and improving the gene expression of relevant odontoblastic markers (Soares, Anovazzi, et al 2018; Cassiano et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Chitosan-Calcium-Simvastatin Scaffold as an Inductive Cell-Free Platform

Soares¹,

Bordini

Bronze‐Uhle³

et al. 2021

J Dent Res

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The development of biomaterials based on the combination of biopolymers with bioactive compounds to develop delivery systems capable of modulating dentin regeneration mediated by resident cells is the goal of current biology-based strategies for regenerative dentistry. In this article, the bioactive potential of a simvastatin (SV)–releasing chitosan-calcium-hydroxide (CH-Ca) scaffold was assessed. After the incorporation of SV into CH-Ca, characterization of the scaffold was performed. Dental pulp cells (DPCs) were seeded onto scaffolds for the assessment of cytocompatibility, and odontoblastic differentiation was evaluated in a microenvironment surrounded by dentin. Thereafter, the cell-free scaffold was adapted to dentin discs positioned in artificial pulp chambers in direct contact with a 3-dimensional (3D) culture of DPCs, and the system was sealed to simulate internal pressure at 20 cm/H2O. In vivo experiments with cell-free scaffolds were performed in rats’ calvaria defects. Fourier-transform infrared spectroscopy spectra proved incorporation of Ca and SV into the scaffold structure. Ca and SV were released upon immersion in a neutral environment. Viable DPCs were able to spread and proliferate on the scaffold over 14 d. Odontoblastic differentiation occurred in the DPC/scaffold constructs in contact with dentin, in which SV supplementation promoted odontoblastic marker overexpression and enhanced mineralized matrix deposition. The chemoattractant potential of the CH-Ca scaffold was improved by SV, with numerous viable and dentin sialoprotein–positive cells from the 3D culture being observed on its surface. Cells at 3D culture featured increased gene expression of odontoblastic markers in contact with the SV-enriched CH-Ca scaffold. CH-Ca-SV led to intense mineralization in vivo, presenting mineralization foci inside its structure. In conclusion, the CH-Ca-SV scaffold induces differentiation of DPCs into a highly mineralizing phenotype in the presence of dentin, creating a microenvironment capable of attracting pulp cells to its surface and inducing the overexpression of odontoblastic markers in a cell-homing strategy.

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Simvastatin-Enriched Macro-Porous Chitosan-Calcium-Aluminate Scaffold for Mineralized Tissue Regeneration

Cited by 8 publications

References 21 publications

Effect of pulp capping materials on odontogenic differentiation of human dental pulp stem cells: An in vitro study

Effect of pulp capping materials on odontogenic differentiation of human dental pulp stem cells: An in vitro study

Assessment of the regenerative potential of macro-porous chitosan-calcium simvastatin scaffolds on bone cells

Chitosan-Calcium-Simvastatin Scaffold as an Inductive Cell-Free Platform

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