Nanomedicine Journal

Nanomedicine Journal

Improving physicochemical, mechanical, and biological properties of a porous polyvinyl alcohol/chitosan matrix via modification with magnesium and silicon agents

Document Type : Research Paper

Authors
Nima Vakili 1
Azadeh Asefnejad 1
Mohammad Mohammadi 1
Hessam Rezaei 1
Amirsalar Khandan 2
1 Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran
2 Dental Research Center, Dental Research Institute, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
10.22038/nmj.2025.79321.1951
Abstract
Objective(s): Biocomposite scaffolds made from polymers and bioactive materials can provide the necessary bioactivity and mechanical properties for bone tissue engineering.
Materials and Methods: In this study, we aimed to evaluate the properties of a novel composite scaffold made from a combination of chitosan, PVA, MgCl₂, and GPTMS as a crosslinking agent. Scanning Electron Microscopy (SEM) and Fourier-Transform Infrared Spectroscopy (FTIR) analysis characterized the prepared composite scaffold. The composite scaffolds' mechanical properties, bioactivity, biocompatibility, swelling, and degradation were also investigated.
Results: Significant improvements in the mechanical properties were observed in the modified composite compared to those seen in the scaffold without MgCl₂. With an increase in MgCl₂ content, the scaffold's degradation and porosity increased, while its swelling capacity decreased. Bioactivity was also enhanced in the composite following the further addition of MgCl₂.
Conclusion:  In vitro tests for cytotoxicity and MG-63 cell proliferation showed that the composite scaffolds were non-cytotoxic, resulting in better cell adherence and growth on the surface of these scaffolds.  
Keywords
PVA-chitosan Scaffolds
Magnesium chloride
GPTMS
Osseoinductivity
Dental materials
  1. Nie L, Chen D, Suo J, Zou P, Feng S, Yang Q, et al. Physicochemical characterization and biocompatibility in vitro of biphasic calcium phsphate/polyvinyl alcohol scaffolds prepared by freeze-drying method for bone tissue engineering applications. Colloids Surf B Biointerfaces. 2012;100:169-176.
  2. Diba M, Kharaziha M, Fathi M, Gholipourmalekabadi M, Samadikuchaksaraei A. Preparation and characterization of polycaprolactone/forsterite nanocomposite porous scaffolds designed for bone tissue regeneration. Compos Sci Technol. 2012;72:716-723.
  3. Ma L, Gao C, Mao Z, Zhou J, Shen J, Hu X, et al. Collagen/chitosan porous scaffolds with improved biostability for skin tissue engineering. Biomaterials. 2003;24:4833-4841.
  4. Sowjanya J, Singh J, Mohita T, Sarvanan S, Moorthi A, Srinivasan N, et al. Biocomposite scaffolds containing chitosan/alginate/nano-silica for bone tissue engineering. Colloids Surf B Biointerfaces. 2013;109:294-300.
  5. Levengood SKL, Zhang M. Chitosan-based scaffolds for bone tissue engineering. J Mater Chem B. 2014;2:3161-184.
  6. Jasemi, A., Moghadas, B. K., Khandan, A., & Saber-Samandari, S. A porous calcium-zirconia scaffolds composed of magnetic nanoparticles for bone cancer treatment: Fabrication, characterization and FEM analysis. Cer Int. 2022; 48(1), 1314-1325.
  7. Tonda-Turo C, Gentile P, Saracino S, Chiono V, Nandagiri VK, Muzio G, et al. Comparative analysis of gelatin scaffolds crosslinked by genipin and silane coupling agent. Int J Biol Macromol. 2011;49:700-706.
  8. Salmani, M. M., Hashemian, M., & Khandan, A. Therapeutic effect of magnetic nanoparticles on calcium silicate bioceramic in alternating field for biomedical application. Cer Int. 2020; 46(17), 27299-27307.
  9. Pandis C, Madeira S, Matos J, Kyritsis A, Mano JF, Ribelles JLG. Chitosan–silica hybrid porous membranes. Mater Sci Eng C. 2014;42:553-561.
  10. Croisier F, Jérôme C. Chitosan-based biomaterials for tissue engineering. Eur Polym J. 2013;49:780-92.
  11. Kadir M, Aspanut Z, Majid S, Arof A. FTIR studies of plasticized poly (vinyl alcohol)–chitosan blend doped with NH4NO3 polymer electrolyte membrane. Spectrochim Acta A Mol Biomol Spectrosc. 2011;78:1068-1074.
  12. Guo R, Hu C, Pan F, Wu H, Jiang Z. PVA–GPTMS/TEOS hybrid pervaporation membrane for dehydration of ethylene glycol aqueous solution. J Membr Sci. 2006;281:454-462.
  13. Peng F, Lu L, Sun H, Wang Y, Wu H, Jiang Z. Correlations between free volume characteristics and pervaporation permeability of novel PVA–GPTMS hybrid membranes. J Membr Sci. 2006;275:97-104.
  14. Kanimozhi K, Basha SK, Kumari VS. Processing and characterization of chitosan/PVA and methylcellulose porous scaffolds for tissue engineering. Mater Sci Eng C. 2016;61:484-91.
  15. Agrawal P, Pramanik K. Chitosan-poly (vinyl alcohol) nanofibers by free surface electrospinning for tissue engineering applications. Tissue Eng Regen Med. 2016;13:485-497.
  16. Shirosaki Y, Okayama T, Tsuru K, Hayakawa S, Osaka A. In vitro bioactivity and MG63 cytocompatibility of chitosan-silicate hybrids. Int J Mater Chem. 2013;3:1-7.
  17. Ding S, Zhang J, Tian Y, Huang B, Yuan Y, Liu C. Magnesium modification up-regulates the bioactivity of bone morphogenetic protein-2 upon calcium phosphate cement via enhanced BMP receptor recognition and Smad signaling pathway. Colloids Surf B Biointerfaces. 2016;145:140-151.
  18. Huang B, Yuan Y, Li T, Ding S, Zhang W, Gu Y, et al. Facilitated receptor-recognition and enhanced bioactivity of bone morphogenetic protein-2 on magnesium-substituted hydroxyapatite surface. Sci Rep. 2016;6.
  19. Foroutan S, Hashemian M, Khandan, AS. A novel porous graphene scaffold prepared using freeze-drying technique for orthopedic approaches: fabrication and buckling simulation using GDQ method. Iran J Mater Sci Eng. 2020; 17(4).
  20. Huan Z, Leeflang S, Zhou J, Zhai W, Chang J, Duszczyk J. In vitro degradation behavior and bioactivity of magnesium‐Bioglass® composites for orthopedic applications. J Biomed Mater Res B Appl Biomater. 2012;100:437-446.
  21. Kheradmandfard M, Fathi M, Ahangarian M, Zahrani EM. In vitro bioactivity evaluation of magnesium-substituted fluorapatite nanopowders. Ceram Int. 2012;38:169-175.
  22. Tang XC, Pikal MJ. Design of freeze-drying processes for pharmaceuticals: practical advice. Pharm Res. 2004;21:191-200.
  23. Searles JA, Carpenter JF, Randolph TW. The ice nucleation temperature determines the primary drying rate of lyophilization for samples frozen on a temperature‐controlled shelf. J Pharm Sci. 2001;90:860-871.
  24. Haugh MG, Murphy CM, O'Brien FJ. Novel freeze-drying methods to produce a range of collagen–glycosaminoglycan scaffolds with tailored mean pore sizes. Tissue Eng Part C Methods. 2009;16:887-984.
  25. Wu H, Tao Z, Gao P, Chen GH. Ice crystal sizes and their impact on microwave assisted freeze drying. Chin J Chem Eng. 2004;12:831-835.
  26. Kumar A, Negi YS, Choudhary V, Bhardwaj NK. Microstructural and mechanical properties of porous biocomposite scaffolds based on polyvinyl alcohol, nano-hydroxyapatite and cellulose nanocrystals. Cellulose. 2014;21:3409-3426.
  27. Cziczo D, Abbatt J. Infrared observations of the response of NaCl, MgCl2, NH4HSO4, and NH4NO3 aerosols to changes in relative humidity from 298 to 238 K. J Phys Chem A. 2000;104:2038-2047.
  28. Sule-Suso J, Forster A, Zholobenko V, Stone N, El Haj A. Effects of CaCl2 and MgCl2 on Fourier transform infrared spectra of lung cancer cells. Appl Spectrosc. 2004;58:61-67.
  29. Wei J, Chen F, Shin JW, Hong H, Dai C, Su J, et al. Preparation and characterization of bioactive mesoporous wollastonite–polycaprolactone composite scaffold. Biomaterials. 2009;30:1080-1088.
  30. Kiani A, Hanna JV, King SP, Rees GJ, Smith ME, Roohpour N, et al. Structural characterization and physical properties of P2O5–CaO–Na2O–TiO2 glasses by Fourier transform infrared, Raman and solid-state magic angle spinning nuclear magnetic resonance spectroscopies. Acta Biomater. 82012;8:333-340.
  31. Clupper DC, Gough JE, Embanga PM, Notingher I, Hench LL, Hall MM. Bioactive evaluation of 45S5 bioactive glass fibres and preliminary study of human osteoblast attachment. J Mater Sci Mater Med. 2004;15:803-808.
  32. Liang H, Mirinejad MS, Asefnejad A, Baharifar H, Li X, Saber-Samandari S, et al. Fabrication of tragacanthin gum-carboxymethyl chitosan bio-nanocomposite wound dressing with silver-titanium nanoparticles using freeze-drying method. Mater Chem Phys. 2022;279:125770.
  33. Karimi M, Asefnejad A, Aflaki D, Surendar A, Baharifar H, Saber-Samandari S, et al. Fabrication of shapeless scaffolds reinforced with baghdadite-magnetite nanoparticles using a 3D printer and freeze-drying technique. J Mater Res Technol. 2021;14:3070-9.
  34. Foroutan S, Hashemian M, Khosravi M, Nejad MG, Asefnejad A, Saber-Samandari S, Khandan A. A porous sodium alginate-CaSiO3 polymer reinforced with graphene nanosheet: fabrication and optimality analysis. Fibers Polym. 2021;22:540-549.
  35. Raisi A, Asefnejad A, Shahali M, Doozandeh Z, Kamyab Moghadas B, Saber-Samandari S, Khandan A. A soft tissue fabricated using a freeze-drying technique with carboxymethyl chitosan and nanoparticles for promoting effects on wound healing. J Nanoanalysis. 2020;7(4):262-274.
  36. Iranmanesh P, Ehsani A, Khademi A, Asefnejad A, Shahriari S, Soleimani M, Khandan A. Application of 3D bioprinters for dental pulp regeneration and tissue engineering (porous architecture). Transp Porous Media. 2022;142(1):265-293.
  37. Jamnezhad S, Asefnejad A, Motififard M, Yazdekhasti H, Kolooshani A, Saber-Samandari S, Khandan A. Development and investigation of novel alginate-hyaluronic acid bone fillers using freeze drying technique for orthopedic field. Nanomed Res J. 2020;5(4):306-315.
  38. Raisi A, Asefnejad A, Shahali M, Sadat Kazerouni ZA, Kolooshani A, Saber-Samandari S, Khandan A. Preparation, characterization, and antibacterial studies of N,O-carboxymethyl chitosan as a wound dressing for bedsore application. Arch Trauma Res. 2020;9(4):181-188.
  39. Li X, Saeed SS, Beni MH, Morovvati MR, Angili SN, Toghraie D, et al. Experimental measurement and simulation of mechanical strength and biological behavior of porous bony scaffold coated with alginate-hydroxyapatite for femoral applications. Compos Sci Technol. 2021;214:108973.
  40. Moarrefzadeh A, Morovvati MR, Angili SN, Smaisim GF, Khandan A, Toghraie D. Fabrication and finite element simulation of 3D printed poly L-lactic acid scaffolds coated with alginate/carbon nanotubes for bone engineering applications. Int J Biol Macromol. 2023;224:1496-1508.
  41. Khandan A, Nassireslami E, Saber-Samandari S, Arabi N. Fabrication and characterization of porous bioceramic-magnetite biocomposite for maxillofacial fractures application. Dent Hypotheses. 2020;11(3):74-85.
  42. Khandan A, Karamian E, Bonakdarchian M. Mechanochemical synthesis evaluation of nanocrystalline bone-derived bioceramic powder using for bone tissue engineering. Dent Hypotheses. 2014;5(4):155-161.
  43. Attaeyan A, Shahgholi M, Khandan A. Fabrication and characterization of novel 3D porous Titanium-6Al-4V scaffold for orthopedic application using selective laser melting technique. Iran J Chem Chem Eng. (IJCCE). 2024;43(1).
  44. Khademi A, Khandan A, Iranmanesh P, Heydari M. Development of a 3D bioprinted alginate-gelatin hydrogel scaffold loaded with calcium phosphates for dental pulp tissue regeneration. Iran J Chem Chem Eng. 2025; 44(01): 1-16.
  45. Safaei MM, Abedinzadeh R, Khandan A, Barbaz-Isfahani R, Toghraie D. Synergistic effect of graphene nanosheets and copper oxide nanoparticles on mechanical and thermal properties of composites: Experimental and simulation investigations. Mater Sci Eng B. 2023;289:116248.
  46. Khandan A, Khosravi M, Roustazadeh D, Aghadavoudi F. Impact of alumina and carbon nanotubes on mechanical properties of a composite: molecular dynamic (MD) simulation. Iran J Chem Chem Eng. 2024; 43 (8): 2866-2877.
  47. Monshi M, Esmaeili S, Kolooshani A, Moghadas BK, Saber-Samandari S, Khandan A. A novel three-dimensional printing of electroconductive scaffolds for bone cancer therapy application. Nanomed J. 2020;7(2).
  48. Montazeran AH, Saber Samandari S, Khandan A. Artificial intelligence investigation of three silicates bioceramics-magnetite bio-nanocomposite: hyperthermia and biomedical applications. Nanomed J. 2018;5(3):163-171.
  49. Rajaei A, Kazemian M, Khandan A. Investigation of mechanical stability of lithium disilicate ceramic reinforced with titanium nanoparticles. Nanomed Res J. 2022;7(4):350-359.
  50. Yekta HJ, Shahali M, Khorshidi S, Rezaei S, Montazeran AH, Samandari SS, Khandan A. Mathematically and experimentally defined porous bone scaffold produced for bone substitute application. Nanomed J. 2018;5(4).
  51. Jafaripour N, Omidvar H, Saber-Samandari S, Mohammadi R, Shokrani Foroushani R, Kamyab Moghadas B, Khandan A. Synthesize and Characterization of a Novel Cadmium Selenide Nanoparticle with Iron Precursor Applicable in Hyperthermia of Cancer Cells. Int J Nanoscience Nanotechnology. 2021;17(2):77-90.
  52. Salimi K, Eghbali S, Jasemi A, Shokrani Foroushani R, Joneidi Yekta H, Latifi M, Khandan A. An artificial soft tissue made of nano-alginate polymer using bioxfab 3D bioprinter for treatment of injuries. Nanochemistry Res. 2020;5(2):120-127.
  53. Fatalla AA, Arzani S, Veseli E, Khademi A, Khandan A, Fahmy MD, Kelishadi R. Revolutionizing systematic reviews and meta-analyses: the role of artificial intelligence in evidence synthesis. Dent Hypotheses. 2023;14(4):93-94.
  54. Mirmohammadi H, Kolahi J, Khandan A. Bibliometric analysis of dental preprints published in 2022. Dent Hypotheses. 2023;14(1):1-2.
  55. Khandan A, Ozada N, Karamian E. Novel microstructure mechanical activated nano composites for tissue engineering applications. J Bioeng Biomed Sci. 2015;5(1):1.

 

Nanomedicine Journal
Volume 12, Issue 3
Summer 2025
Pages 507-517