In vitro and in vivo evaluation of chitosan scaffolds combined with simvastatin-loaded nanoparticles for guided bone regeneration

Xue, Yuhua; Wu, Mingyao; Liu, Zongren; Song, Jinhua J.; Luo, Shuyu; Li, Hongjie; Li, Yuan; Jin, Lichun; Guan, Binbin; Lin, Mingli; Chen, Fuyu; Jin, Can; Liu, Deping; Li, Yanqiu; Zhang, Xu

doi:10.1007/s10856-019-6249-3

Cited by 28 publications

(15 citation statements)

References 47 publications

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“…Since the IL‒6 can be involved in many pathways [38] and its role in differentiation was already demonstrated [6], we can suggest a role for this interleukin in the bone formation happening in our experimental model. On the other hand, the ability of chitosan, whose modified form, Chitlac, coats the thermosets, to promote osteogenesis is so largely proven, that it has been recently studied in combination with other biomaterials in bone regeneration [39,40].…”

Section: Discussionmentioning

confidence: 99%

Chitlac-Coated Thermosets Enhance Osteogenesis and Angiogenesis in a Co-culture of Dental Pulp Stem Cells and Endothelial Cells

et al. 2019

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Dental pulp stem cells (DPSCs) represent a population of stem cells which could be useful in oral and maxillofacial reconstruction. They are part of the periendothelial niche, where their crosstalk with endothelial cells is crucial in the cellular response to biomaterials used for dental restorations. DPSCs and the endothelial cell line EA.hy926 were co-cultured in the presence of Chitlac-coated thermosets in culture conditions inducing, in turn, osteogenic or angiogenic differentiation. Cell proliferation was evaluated by 3–[4,5–dimethyl–thiazol–2–yl–]–2,5–diphenyl tetrazolium bromide (MTT) assay. DPSC differentiation was assessed by measuring Alkaline Phosphtase (ALP) activity and Alizarin Red S staining, while the formation of new vessels was monitored by optical microscopy. The IL-6 and PGE2 production was evaluated as well. When cultured together, the proliferation is increased, as is the DPSC osteogenic differentiation and EA.hy926 vessel formation. The presence of thermosets appears either not to disturb the system balance or even to improve the osteogenic and angiogenic differentiation. Chitlac-coated thermosets confirm their biocompatibility in the present co-culture model, being capable of improving the differentiation of both cell types. Furthermore, the assessed co-culture appears to be a useful tool to investigate cell response toward newly synthesized or commercially available biomaterials, as well as to evaluate their engraftment potential in restorative dentistry.

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Section: Discussionmentioning

confidence: 99%

Chitlac-Coated Thermosets Enhance Osteogenesis and Angiogenesis in a Co-culture of Dental Pulp Stem Cells and Endothelial Cells

et al. 2019

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“…The new bone formation was more evident in CH-Ca-SV, with various mineralization foci being detected not only at the borders but also inside the scaffold structure. The potential of SV as a biological cue in cell-homing strategies has been demonstrated by previous in vivo studies in which SV-loaded scaffolds improved critical-size bone defect regeneration as well as hastened the fracture-healing and union process (Xue et al 2019; Zhang et al 2019; Hajializade et al 2020). Researchers have found that SV acts as an activator to enhance the regeneration of bone defects along with hydroxyapatite ceramics in different scaffold formulations (Wang et al 2018).…”

Section: Discussionmentioning

confidence: 95%

“…Another strategy to improve and fasten neo-tissue-genesis is to incorporate a bioactive cue on scaffold composition. Local simvastatin (SV) delivery is a strategy successfully used to increase and anchor bone regeneration by creating scaffolds capable of releasing bioactive dosages of this drug at the application site (Li et al 2018; Wang et al 2018; Xue et al 2019; Zhang et al 2019; Hajializade et al 2020). Chitosan has been considered a suitable carrier system for poorly soluble drugs, such as SV, increasing its solubility and thereby its bioavailability for several clinical applications (Selvasudha and Koumaravelou 2017).…”

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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“…However, the low mechanical properties of scaffolds prepared from chitosan make its clinical application problematic. An effective method to overcome chitosan's drawbacks is to blend it with synthetic polymers [249][250][251][252]. Skop et al designed biocompatible chitosan microspheres for the delivery of neural stem cells and growth factors for CNS injuries [253]; another group designed chitosan particles loaded with the drug piperine, reported to have neuroprotective potential against Alzheimer's disease, which successfully targeted specific areas of the brain [254].…”

Section: Chitin and Chitosanmentioning

confidence: 99%

Piezoelectric Scaffolds as Smart Materials for Neural Tissue Engineering

2020

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Injury to the central or peripheral nervous systems leads to the loss of cognitive and/or sensorimotor capabilities, which still lacks an effective treatment. Tissue engineering in the post-injury brain represents a promising option for cellular replacement and rescue, providing a cell scaffold for either transplanted or resident cells. Tissue engineering relies on scaffolds for supporting cell differentiation and growth with recent emphasis on stimuli responsive scaffolds, sometimes called smart scaffolds. One of the representatives of this material group is piezoelectric scaffolds, being able to generate electrical charges under mechanical stimulation, which creates a real prospect for using such scaffolds in non-invasive therapy of neural tissue. This paper summarizes the recent knowledge on piezoelectric materials used for tissue engineering, especially neural tissue engineering. The most used materials for tissue engineering strategies are reported together with the main achievements, challenges, and future needs for research and actual therapies. This review provides thus a compilation of the most relevant results and strategies and serves as a starting point for novel research pathways in the most relevant and challenging open questions.

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In vitro and in vivo evaluation of chitosan scaffolds combined with simvastatin-loaded nanoparticles for guided bone regeneration

Cited by 28 publications

References 47 publications

Chitlac-Coated Thermosets Enhance Osteogenesis and Angiogenesis in a Co-culture of Dental Pulp Stem Cells and Endothelial Cells

Chitlac-Coated Thermosets Enhance Osteogenesis and Angiogenesis in a Co-culture of Dental Pulp Stem Cells and Endothelial Cells

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

Piezoelectric Scaffolds as Smart Materials for Neural Tissue Engineering

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