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Microfluidic Fabrication of Alendronate-Loaded Chitosan Nanoparticles for Enhanced Osteogenic Differentiation of Stem Cells Publisher Pubmed



Moradikhah F1 ; Doostitelgerd M2, 3 ; Shabani I1 ; Soheili S4 ; Dolatyar B5 ; Seyedjafari E6
Authors
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Authors Affiliations
  1. 1. Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran
  2. 2. Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran
  4. 4. Department of Polymer and Color Engineering, Amirkabir University of Technology, Tehran, Iran
  5. 5. Department of Cell and Developmental Biology, School of Biological Sciences, College of Science, University of Tehran, Tehran, Iran
  6. 6. Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran

Source: Life Sciences Published:2020


Abstract

Aims: In this study, we used a cross-junction microfluidic device for preparation of alendronate-loaded chitosan nanoparticles with desired characteristics to introduce a suitable element for bone tissue engineering scaffolds. Main methods: By controlling the reaction condition in microfluidic device, six types of alendronate-loaded chitosan nanoparticles were fabricated which had different physical properties. Hydrodynamic diameter of synthetized particles was evaluated by dynamic light scattering (102 to 215 nm). Nanoparticle morphology was determined by SEM and AFM images. The osteogenic effects of prepared selected nanoparticles on human adipose stem cells (hA-MSCs) were evaluated by assessment of alkaline phosphatase (ALP) activity, calcium deposition, ALP and osteopontin gene expression. Key findings: The highest loading efficiency percentage (%LE) was %32.42 ± 2.02. Based on MTT assessment, two samples which had no significant cytotoxicity were chosen for further studies (particle sizes and %LE were 142 ± 6.1 nm, 198 ± 16.56 nm, %16.76 ± 3.91 and %32.42 ± 2.02, respectively). In vitro release behavior of nanoparticles displayed pH responsive characteristics. Significant faster release was seen in acidic pH = 5.8 than neutral pH = 7.4. The selected nanoparticles demonstrated higher ALP activity at 14 days in comparison to selected blank sample and osteogenic differentiation media (ODM) and a downregulation at 21 days in comparison to 14 days. Calcium content assay at 21 days displayed significant differences between alendronate-loaded nanoparticles and ODM. ALP and osteopontin mRNA expression was significantly higher than the cells cultured in ODM at 14 and 21 days. Significance: We concluded that our prepared nanoparticles significantly enhanced osteogenic differentiation of hA-MSCs and can be a suitable compartment of bone tissue engineering scaffolds. © 2020
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