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Biocompatibility of Veratric Acid–Encapsulated Chitosan/Methylcellulose Hydrogel: Biological Characterization, Osteogenic Efficiency with In Silico Molecular Modeling

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Abstract

The limitations of graft material, and surgical sites for autografts in bone defects treatment have become a significant challenge in bone tissue engineering. Phytocompounds markedly affect bone metabolism by activating the osteogenic signaling pathways. The present study investigated the biocompatibility of the bio-composite thermo-responsive hydrogels consisting of chitosan (CS), and methylcellulose (MC) encapsulated with veratric acid (VA) as a restorative agent for bone defect treatment. The spectroscopy analyses confirmed the formation of CS/MC hydrogels and VA encapsulated CS/MC hydrogels (CS/MC-VA). Molecular analysis of the CS-specific MC decamer unit with VA complex exhibited a stable integration in the system. Further, Runx2 (runt-related transcription factor 2) was found in the docking mechanism with VA, indicating a high binding affinity towards the functional site of the Runx2 protein. The formulated CS/MC-VA hydrogels exhibited biocompatibility with the mouse mesenchymal stem cells, while VA promoted osteogenic differentiation in the stem cells, which was verified by calcium phosphate deposition through the von Kossa staining. The study results suggest that CS/MC-VA could be a potential therapeutic alternative source for bone regeneration.

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Data Availability

Data that support the findings of this study will be available from the corresponding author upon reasonable request.

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Acknowledgements

All the authors were grateful to the authorities of their institutes and Researchers Supporting Project number (RSP-2023-R20), King Saud University, Riyadh, Saudi Arabia.

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Author notes

  1. Kaliannan Durairaj

    Present address: Zoonosis Research Center, Department of Infection Biology, School of Medicine, Wonkwang University, 54538, Iksan, Republic of Korea

Authors and Affiliations

  1. Department of Environmental Science, School of Life Sciences, Periyar University, Salem, 636 011, India

    Kaliannan Durairaj

  2. Department of Food Science and Biotechnology, College of Life Science, Sejong University, Seoul, 05006, South Korea

    Balamuralikrishnan Balasubramanian & Sungkwon Park

  3. Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore- 641 046, Tamil Nadu, India

    Vijaya Anand Arumugam

  4. Computational Biology Lab, Department of Bioinformatics, Bharathiar University, Coimbatore-46, Tamil Nadu, India, 641046

    Murugesh Easwaran

  5. Division of Food Science and Technology Management, Faculty of Science and Technology, Rajamangala University of Technology Thanyaburi, Khlong Hok, 12110, Thailand

    Utthapon Issara

  6. Department of Zoology, School of Biosciences, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, 641 043, Tamil Nadu, India

    Karthika Pushparaj

  7. Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    Naif Abdullah Al-Dhabi & Mariadhas Valan Arasu

  8. Department of Animal Science, College of Agriculture, Guangdong Ocean University, Zhanjiang, Guangdong, 524088, People’s Republic of China

    Wen-Chao Liu

  9. Department of Fruit and Vegetable Product Technology, Prof. Wacław Dąbrowski Institute of Agricultural and Food Biotechnology – State Research Institute, 36 Rakowiecka St., 02-532, Warsaw, Poland

    Amin Mousavi Khaneghah

  10. Department of Technology of Chemistry, Azerbaijan State Oil and Industry University, Baku, Azerbaijan

    Amin Mousavi Khaneghah

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  1. Kaliannan Durairaj
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Contributions

Conceptualization, DK, BB, AMK, and WL; data curation, DK, BB, KP, VA; formal analysis and methodology, DK, KP, VA; formal analysis and bioinformatics, ME; writing—original draft preparation, BB and DK; data analysis and interpretation, NAA, WL, AMK; writing—review and editing, BB, MVA, NAA, SP, UI, VA, AMK, and WL; recourses and validation WL, BB. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Kaliannan Durairaj or Amin Mousavi Khaneghah.

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Balamuralikrishnan Balasubramanian equally contributed as a first author.

Highlights

• Veratric acid (VA) is a phenolic phytocompound as potential use for clinical use.

• The VA-loaded chitosan and methylcellulose hydrogels (CS/MC-VA) was prepared.

• The bioavailability and osteogenic efficacy were investigated with molecular modeling analysis.

• The CS/MC-VA showed no cytotoxic effects on to mouse mesenchymal stem cells.

• The CS/MC-VA showed potential osteogenic efficacy for bone regeneration.

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Durairaj, K., Balasubramanian, B., Arumugam, V.A. et al. Biocompatibility of Veratric Acid–Encapsulated Chitosan/Methylcellulose Hydrogel: Biological Characterization, Osteogenic Efficiency with In Silico Molecular Modeling. Appl Biochem Biotechnol 195, 4429–4446 (2023). https://doi.org/10.1007/s12010-023-04311-5

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