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Synergistic enhancement of osteogenesis: silica nanoparticles and proanthocyanidin on bioinspired nanofibrous scaffolds for craniofacial bone regeneration

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Abstract

The reconstruction of craniofacial bone defects is a significant challenge in regenerative medicine due to the limitations of standard grafts. In this study, we developed innovative, multifunctional, nanostructured scaffolds derived from Phlomis Monocephala leaves to address this issue. These fibrous cellulose scaffolds were coated with Grape Seed Proanthocyanidin Extract and Silica Nanoparticles, individually and in combination, to enhance their properties for bone tissue engineering applications. The scaffolds were meticulously evaluated for their morphology, chemical composition, swelling behavior, protein adsorption, hydrophilicity, porosity, and their ability to support cell survival, proliferation, and differentiation into bone cells. The scaffolds functionalized with both Grape Seed Proanthocyanidin Extract and Silica Nanoparticles exhibited the most favorable properties, significantly promoting the differentiation of human bone marrow mesenchymal stem cells into osteogenic cells. This was evidenced by increased alkaline phosphatase activity, matrix mineralization, collagen formation, and the expression of genes related to bone formation. Additionally, these nanostructured scaffolds demonstrated superior antibacterial activity against both Gram-positive and Gram-negative bacteria compared to uncoated scaffolds. In vivo biocompatibility assessments revealed that the Grape Seed Proanthocyanidin Extract and Silica Nanoparticles-coated scaffolds performed excellently in terms of re-epithelialization, vascularization, and reducing inflammation, showcasing their potential for future clinical applications. Our findings highlight the immense potential of these nanostructured scaffolds as biocompatible materials for treating bone tissue defects, offering a novel and effective approach in the field of nanotechnology and regenerative medicine.

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The experimental data will be provided by the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to acknowledge the valuable assistance provided by the members of the Laboratory of Reconstructive Medicine and Biomedical Innovations, Pasteur Institute of Iran. Further, we do appreciate Mr. Saeed Javadi Anaghizi of Central Laboratory of the Shahid Beheshti University for his technical support.

Funding

This research received partial support from the Center for International Scientific Studies and Collaboration (CISSC) of Ministry of Science, Research and Technology of Iran., Grant No. 4010221 to M.J and from Shahid Beheshti Uni Grant No. 1402 to HS.

Author information

Author notes

  1. Atena Galefi, Saadi Hosseini and Atefeh Alipour contributed equally to this work.

Authors and Affiliations

  1. Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, 19839-69411, Iran

    Atena Galefi, Rezvaneh Banaeyan, Naser Farrokhi, Hosein Shahsavarani & Mehdi Jahanfar

  2. Laboratory of Regenerative Medicine and Biomedical Innovations, National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, 13169-43551, Iran

    Atena Galefi, Saadi Hosseini, Atefeh Alipour, Rezvaneh Banaeyan, Amir Amanzadeh & Hosein Shahsavarani

  3. Department of Nanobiotechnology, Pasteur Institute of Iran, Tehran, 13169-43551, Iran

    Atefeh Alipour

  4. Oujiang Laboratory, Key Laboratory of Alzheimer’s Disease of Zhejiang Province, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China

    Peng-Yuan Wang

  5. Department of Biomedical Engineering, Faculty of Engineering & Natural Sciences, Istinye University, Istanbul, Turkey

    Ali Zarrabi

  6. Graduate School of Biotechnology and Bioengineering, Yuan Ze University, Taoyuan, 320315, Taiwan

    Ali Zarrabi

  7. Department of Research Analytics, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College and Hospitals, Saveetha University, Chennai, 600 077, India

    Ali Zarrabi

  8. Iranian Biological Resource Center, Academic Center for Education, Culture, and Research (ACECR), Tehran, 1533734716, Iran

    Hosein Shahsavarani

  9. Center for International Scientific Studies and Collaborations (CISSC), Ministry of Science, Research and Technology, Tehran, 19839-69411, Iran

    Mehdi Jahanfar

Authors
  1. Atena Galefi
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  2. Saadi Hosseini
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  3. Atefeh Alipour
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  4. Rezvaneh Banaeyan
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  5. Naser Farrokhi
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  6. Amir Amanzadeh
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  7. Peng-Yuan Wang
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  8. Ali Zarrabi
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  9. Hosein Shahsavarani
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  10. Mehdi Jahanfar
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Contributions

A.G. and S.H.: experimental design, conducting experiments, analyzing the data, performing statistical analyses, writing initial version of the manuscript. H.S., A.A. and M.J.: conceptualization, supervision of the project, securing funds, checking the data, writing- reviewing and editing. R.B., A.A. and P.Y.W.: data analysis. A.Z. and N.F.: revising and further analyzing the data, and critically revising the manuscript. All authors have read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Ali Zarrabi, Hosein Shahsavarani or Mehdi Jahanfar.

Ethics declarations

Ethical approval

All animal experiments, including surgical procedures, were conducted by the National Research Council’s Guide for the Care and Use of Laboratory Animals (8th Ed.). The study received approval from the ethics committee of Shahid Beheshti University (No. IR.SBU.REC.1400.1011).

Consent to participate

The research did not involve human participants.

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The research did not involve human participants.

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The authors declare that they have no conflict of interest.

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Galefi, A., Hosseini, S., Alipour, A. et al. Synergistic enhancement of osteogenesis: silica nanoparticles and proanthocyanidin on bioinspired nanofibrous scaffolds for craniofacial bone regeneration. emergent mater. (2024). https://doi.org/10.1007/s42247-024-00909-5

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  • DOI: https://doi.org/10.1007/s42247-024-00909-5

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