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Tissue Plasminogen Activator Loaded PCL Nanofibrous Scaffold Promoted Nerve Regeneration After Sciatic Nerve Transection in Male Rats

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Abstract

According to the studies, damages to the peripheral nerve as a result of a trauma or acute compression, stretching, or burns accounts for a vast range of discomforts which strongly impressed the patient’s life quality. Applying highly potent biomolecules and growth factors in the damaged nerve site would promote the probability of nerve regeneration and functional recovery. Tissue plasminogen activator (tPA) is one of the components that can contribute importantly to degenerating and regenerating the peripheral nerves following the injuries occurred and the absence of this biomolecule hinders the recoveries of the nerves. This technique would guarantee the direct accessibility of tPA for the regenerating axons. Structural, physical, and in vitro cytotoxicity evaluations were done before in vivo experiments. In this study, twenty-four mature male rats have been exploited. The rats have been classified into four groups: controls, axotomy, axotomy + scaffold, and axotomy + tPA-loaded scaffold. Four, 8, and 12 weeks post-surgical, the sciatic functional index (SFI) has been measured. After 12 weeks, the spinal cord, sciatic nerve, and dorsal root ganglion specimens have been removed and stereological procedures, immunohistochemistry, and gene expression have been used to analyze them. Stereological parameters, immunohistochemistry of GFAP, and gene expression of S100, NGF, and BDNF were significantly enhanced in tPA-loaded scaffold group compared with axotomy group. The most similarity was observed between the results of control group and tPA-loaded scaffold group. According to the results, a good regeneration of the functional nerve tissues in a short time was observed as a result of introducing tPA.

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Acknowledgments

Animal studies of this work were performed at Hearing Disorders Research Center, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Therefore, In vivo part of this study is derived from the thesis formulated by Ensieh Sajadi, the MSc student at Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran (Registration No. 1397-270).

Funding

This article was financially supported by the Hearing Disorders Research Center, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran (grant number: 91-6124).

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Authors and Affiliations

  1. Hearing Disorders Research Center, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Ensieh Sajadi & Mohammad-Amin Abdollahifar

  2. Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Ensieh Sajadi, Abbas Aliaghaei, Reza Mastery Farahni, Mohammad Bagheri, Saba Ilkhani & Mohammad-Amin Abdollahifar

  3. Department of Anatomical Sciences, Lorestan University of Medical Sciences, Khorramabad, Iran

    Ali Rashidiani-Rashidabadi

  4. Department of Anatomical Sciences, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Amir Raoofi

  5. Department of Anatomy and Neuroscience, faculty of Medicine, Dentistry and Health Science, University of Melbourne, Melbourne, VIC, Australia

    Yousef Sadeghi

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  1. Ensieh Sajadi
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Contributions

MAA and ES designed this study and provided the clinical data and sample. ARR and AR carried out the animal model and immunohistochemistry. AA performed the statistical analysis. RMF wrote and drafted the manuscript. MB and YS carried out the real-time PCR. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mohammad-Amin Abdollahifar.

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The authors declare that they have no conflict of interest.

Ethical Approval

All procedures were approved by the Medical Ethics Committee at Shahid Beheshti University of Medical Sciences, Tehran, Iran (IR.SBMU.MSP.REC. 1396.544).

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Sajadi, E., Aliaghaei, A., Farahni, R.M. et al. Tissue Plasminogen Activator Loaded PCL Nanofibrous Scaffold Promoted Nerve Regeneration After Sciatic Nerve Transection in Male Rats. Neurotox Res 39, 413–428 (2021). https://doi.org/10.1007/s12640-020-00276-z

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