Managol Kayyal - Student research committee, Faculty of medicine, Qazvin University of Medical School, Qazvin, Iran.
Navid Jamali - Department of Biotechnology,College of Science,University of Tehran,Tehran, Iran.
Reyhaneh Abolghasemi - New hearing technologies research center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Esmat Davoudi- Monfared - MD, Assistant Professor, Health Management Research Center & Department of Community Medicine, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Fakhri Allahyari - MD, Assistant Professor, Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Gholamreza Farzanegan - MD, Associate Professor, Trauma Research Center & Department of Neurosurgery, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Mahdi Sharif-Alhoseini - Sina Trauma and Surgery Research Center, Sina Hospital, Tehran Ubniversity of Medical Sciences,Tehran, Iran.

Background: Chronic spinal cord injury has complicated pathophysiology, and current therapies cannot restitute deficits in neurological functions. This review summarizes assembled knowledge of evidence-based medicine and highlights possible challenges.Methods: Review in systematic reviews refer to the review compiling evidence from several reviews into accessible and usable documents. The PubMed, Google Scholar, and Cochrane Library databases were searched by keywords in title and abstracts for articles satisfying the inclusion criteria through September ۳۰, ۲۰۲۲. Two trained investigators independently performed the critical appraisal of systematic review papers with the PRISMA ۲۰۲۰ checklist. Results: The results were presented in the PRISMA flow diagram. After the exclusion, significant findings resulted in the nine final reviewed studies. The Neuropathology of the chronic phase is determined by the stabilization of the lesion, including white matter demyelination, fibrotic scar, and cystic cavitation. Multiple stem cell types and glial cells are studied in regenerative medicine therapies for chronic spinal cord injury. Also, cell and tissue products, gene therapy products, and xenogeneic cell products are other candidates for clinical applications. Synthetic or natural tissue engineering materials can be implanted in solid scaffolds or injectable in situ forming hydrogels, acting as vehicles for the cells or as vectors of therapeutic agents, or filling the cysts in the case of chronic lesions.Conclusion: Combinatorial therapeutic process that employs cells, biomaterials, and soluble molecules to address different appearances of injury will probably provide the definitive solution by regulating the balance between the inhibitory and excitatory factors implicated in chronic spinal cord injury.

review, cell therapy, Biomaterials, Biomolecules