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Neuroregenerative and neuroprotective effects of bioengineered scaffolds in spinal cord injury: a systematic review of preclinical and early phase clinical studies

Spinal Cord volume 63, pages 451–469 (2025)Cite this article

Subjects

Abstract

Study design

Systematic Review

Objectives

To systematically examine the use of bioengineered scaffolds, with/without bioactive agents, drugs, or cellular transplants in preclinical animal models and human studies of spinal cord injury (SCI).

Setting

Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences

Methods

A systematic review and meta-analysis was conducted following PRISMA guidelines and registered in PROSPERO (ID: CRD42023437266). A comprehensive search in MEDLINE and Embase on 8/27/2023 identified studies on scaffolds as neuroregenerative and neuroprotective treatments for SCI. Human studies were assessed using ROBINS-I, and meta-analysis focused on clinical outcomes.

Results

Of 4561 articles screened, 931 studies were included: in-vivo (82%), in-vitro (16%), and human studies (1%). Various biomaterials (N = 82; natural: 38%; synthetic: 62%), cell types (N = 27; NSCs: 24%, Schwann cells: 13%, NPCs: 12%), bioactive agents (N = 38; NT-3: 32%, BDNF: 25%, FGF: 24%), and pharmacological agents (N = 88; chABC: 12%, heparin: 11%, taxels: 10%) were analyzed. Fourteen human studies included acute and chronic SCI patients, with cervical (36%) and thoracic SCI (64%). Clinical trials demonstrated moderate to low quality (ROBINS-I). Our meta-analysis indicated that the pooled 2-scale AIS conversion rate was 30.59% (p = 0.005) ranging from 33.46% (p = 0.036) in acute to 28.35% (p = 0.084) in chronic SCI. Furthermore, the pooled 1-scale AIS conversion rate was 11.79% (p = 0.011), spanning from 17.31% (p = 0.131) in acute to 7.44% (p = 0.081) in chronic SCI.

Conclusion

Scaffold implantation shows promising neuroregenerative potential, evidenced by AIS grade improvement in human studies. Scaffolds are advancing rapidly from laboratory research to clinical trials, expanding treatment options for SCI.

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Fig. 6: AIS conversion rates and assessment of publication bias in human studies of implantation.

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Acknowledgements

M.G.’s contribution to this article was made in the context of the Oxford Global Neurosurgery Initiative.

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Authors and Affiliations

  1. Student Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Armin Khavandegar

  2. Center for Orthopedic Trans-Disciplinary Applied Research, Tehran University of Medical Sciences, Tehran, Iran

    Armin Khavandegar & Negin Safari Dehnavi

  3. Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences (TUMS), Tehran, Iran

    Armin Khavandegar, Zahra Ramezani, Elaheh Khodadoust, Mahgol Sadat Hassan Zadeh Tabatabaei, Kimia RayatSanati & Mahdi Sharif-Alhoseini

  4. School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran

    Negin Safari Dehnavi, Tahereh Maleki, Mahsa Esmaeili & Ayda Eslami Nejad Parizi

  5. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK

    Mario Ganau

  6. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Maryam Alsadat Mousavi

  7. Graduate Biomedical Science Program, University of Alabama at Birmingham, Birmingham, AL, USA

    Kimia RayatSanati

  8. Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Amgad S. Hanna

  9. Department of Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Amgad S. Hanna

  10. Biodiscovery Institute, University of Nottingham, Nottingham, UK

    Zahra Hassannejad

  11. Division of Neurosurgery and Spine Program, University of Toronto, Toronto, ON, Canada

    Michael G. Fehlings

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Contributions

AKh and NS conducted independent screenings of the titles and abstracts to assess eligibility, with ZR providing final approval in cases of discrepancies. Data extraction was performed independently by three pairs: EKh and MH, MM and KR, and ME and AE, with TM consulted for final approval in cases of discrepancies. AKh and MS performed data analysis and visualization. AKh wrote the manuscript, while AKh, MS, and ZH contributed to the conceptualization of the study. Supervision was provided by MGF, MG, ASH, and MS Project administration was led by MS. All authors reviewed and provided critical feedback on the manuscript.

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Correspondence to Mahdi Sharif-Alhoseini.

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(Dr. Michael Fehlings as Editor-in-Chief of Spinal Cord had no role in the peer review or adjudication of this manuscript).

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This study was reviewed and approved by the Ethics Committee of Tehran University of Medical Sciences, with the approval code.

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Khavandegar, A., Safari Dehnavi, N., Ganau, M. et al. Neuroregenerative and neuroprotective effects of bioengineered scaffolds in spinal cord injury: a systematic review of preclinical and early phase clinical studies. Spinal Cord 63, 451–469 (2025). https://doi.org/10.1038/s41393-025-01114-9

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