Effect of Artemisinin-Loaded Mesoporous Cerium-Doped Calcium Silicate Nanopowder on Cell Proliferation of Human Periodontal Ligament Fibroblasts.

Ioannis Tsamesidis,Dimitrios Gkiliopoulos,Karine Reybier,Pierre Perio,Konstantinos M Paraskevopoulos,Anna Theocharidou,Evgenia Lymperaki,Chrysanthi Papoulia,Georgia K Pouroutzidou,Eleana Kontonasaki

doi:10.3390/nano11092189

Abstract

Ion doping has rendered mesoporous structures important materials in the field of tissue engineering, as apart from drug carriers, they can additionally serve as regenerative materials. The purpose of the present study was the synthesis, characterization and evaluation of the effect of artemisinin (ART)-loaded cerium-doped mesoporous calcium silicate nanopowders (NPs) on the hemocompatibility and cell proliferation of human periodontal ligament fibroblasts (hPDLFs). Mesoporous NPs were synthesized in a basic environment via a surfactant assisted cooperative self-assembly process and were characterized using Scanning Electron Microscopy (SEM), X-ray Fluorescence Spectroscopy (XRF), Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Diffraction Analysis (XRD) and N2 Porosimetry. The loading capacity of NPs was evaluated using Ultrahigh Performance Liquid Chromatography/High resolution Mass Spectrometry (UHPLC/HRMS). Their biocompatibility was evaluated with the MTT assay, and the analysis of reactive oxygen species was performed using the cell-permeable ROS-sensitive probe 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA). The synthesized NPs presented a mesoporous structure with a surface area ranging from 1312 m2/g for undoped silica to 495 m2/g for the Ce-doped NPs, excellent bioactivity after a 1-day immersion in c-SBF, hemocompatibility and a high loading capacity (around 80%). They presented ROS scavenging properties, and both the unloaded and ART-loaded NPs significantly promoted cell proliferation even at high concentrations of NPs (125 μg/mL). The ART-loaded Ce-doped NPs with the highest amount of cerium slightly restricted cell proliferation after 7 days of culture, but the difference was not significant compared with the control untreated cells.

Highlights

Mesoporous materials have attracted considerable interest in the field of medicine.They present distinct advantages such as large surface area and tunable pore structure that render them ideal carriers for drug delivery, especially in combination with biologically active ions (e.g., Ca, Ce, Mg, Cu ions) [1,2]
In agreement with previous results regarding the advantageous role of artemisinin in dental pulp stem cells (DPSC), bone marrow-derived mesenchymal stem cells (BMSCs) and in human mesenchymal stem cells, we have shown that human periodontal ligament fibroblasts are positively affected by artemisinin
Liferation of human ligament fibroblasts; at the highest cerium centration, a mild restriction of cell viability was evidenced after 7 days of culture

Summary

Introduction

Mesoporous materials have attracted considerable interest in the field of medicine They present distinct advantages such as large surface area and tunable pore structure that render them ideal carriers for drug delivery, especially in combination with biologically active ions (e.g., Ca, Ce, Mg, Cu ions) [1,2]. Calcium-doped mesoporous materials exhibit improved properties such as a stable mesh structure, high surface area and high bioactivity [4–6]. Both calcium and silicate ions can promote bone regeneration and increase bone mineral density in vivo [7–9], while a few studies have unraveled the effectiveness of bioactive mesoporous calcium-silicate nanoparticles on the apical sealing of teeth root canals [10] and the odontogenic differentiation of human dental pulp stem cells [11]. Magnesium and strontium doped calcium silicates have shown promising properties as drug carriers or as bone regenerative materials [12–15]

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