10.1007/s40204-022-00209-3

Sustained release of valproic acid loaded on chitosan nanoparticles within hybrid of alginate/chitosan hydrogel with/without stem cells in regeneration of spinal cord injury

  • Mohammad Amin Jafarimanesh1,
  • Jafar Ai*2,
  • Shahrokh Shojaei3,
  • Hossein Ali Khonakdar4,
  • Goldis Darbemamieh1,
  • Sadegh Shirian5,
  1. Department of Biomedical Engineering, Central Tehran Branch, Islamic Azad University, Tehran, IR
  2. Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417743361, IR
  3. Department of Biomedical Engineering, Central Tehran Branch, Islamic Azad University, Tehran, IR Central Tehran Branch, Stem Cells Research Center, Tissue Engineering and Regenerative Medicine Institute, Islamic Azad University, Tehran, IR
  4. Department of Processing, Iran Polymer and Petrochemical Institute, Tehran, IR Reactive Processing, Leibniz Institute of Polymer Research Dresden, Dresden, DE
  5. Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, IR Shiraz Molecular Pathology Research Center, Dr Daneshbod Path Lab, Shiraz, IR Shefa Neurosciences Research Center, Khatam-Alanbia Hospital, Tehran, IR

Published 2023-01-18

How to Cite

Jafarimanesh, M. A., Ai, J., Shojaei, S., Khonakdar, H. A., Darbemamieh, G., & Shirian, S. (2023). Sustained release of valproic acid loaded on chitosan nanoparticles within hybrid of alginate/chitosan hydrogel with/without stem cells in regeneration of spinal cord injury. Progress in Biomaterials, 12(2 (June 2023). https://doi.org/10.1007/s40204-022-00209-3
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Abstract

Abstract Hydrogels have been increasingly applied in tissue regeneration and drug delivery systems (DDS). In this study, the capacity of valproic acid (Val) encapsulated within hybrid of alginate (Alg)-chitosan (Cs) (Alg-Cs) hydrogel containing Cs nanoparticle (Npch) with/without human endometrial stem cells (hEnSC) was initially examined for regeneration of spinal cord injury (SCI). To evaluate the stability of the synthesized hydrogels zeta potential necessary measurements were made. Physicochemically, the developed hydrogels were evaluated using Fourier-transform infrared (FTIR) spectroscopy. The physical properties including degradation rate, swelling ability, and tunability of the synthesized hydrogels were studied. To evaluate the nerve regeneration ability of the synthesized hydrogels, 35 Sprague–Dawley rats were undergone SCI. The spinal cords were exposed using laminectomy in T9-T10 area and the hemi-section SCI model was made. The rats were then randomly divided into 5 groups ( n  = 7) including, Alg-Cs/Npch, Alg-Cs/Npch/hEnSCs, Alg-Cs/Npch/Val, and Alg-Cs/Npch/hEnScs/Val, and the control groups without any intervention. The FTIR spectra showed band frequencies and assignments of Val, Alg-Cs, and alginate. Nanoparticles were formulated with a mean diameter of 187 and 210 nm, for Val/Alg-Cs and Alg-Cs, respectively. The loading of Val into Alg-Cs led to its reduced size by about 40 nm. The Cs-Npch/Val hydrogels degraded faster than the Alg-Cs-/Npch/Val hydrogel specifically in extended time of incubation. A higher swelling capacity of Alg-Cs/Npch hydrogel, compared to Cs/Npch/Val and Alg-Cs/Npch/Val hydrogels, was found. The Cs-Npch/Val hydrogels degraded faster than Alg-Cs-/Npch/Val hydrogel. The Alg-Cs/Npch/hEnSCs/Val could regenerate the damaged nerve fibers and histologically prevent the SCI-induced vacuolization spaces. The prepared Alg-Cs/Npch/Val could be a suitable polymeric carrier for taurine drugs as bioactive substrate in nerve tissue engineering (NTE) and DDS.

Keywords

  • Valproic acid,
  • Chitosan,
  • Polysaccharide-based hydrogel

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