Chitosan-Based Hydrogels for Spinal Cord Regeneration: A Systematic Review of Preclinical Evidence, Regenerative Mechanisms, and Translational Challenges

Tissue engineering products, especially hydrogels, have been evaluated in many studies for spinal cord regeneration due to their injectability and similar deformability to the target tissue. In particular, chitosan has been used in many studies along with other polymers due to their biocompatibility, biodegradability, antibacterial properties, and the creation of an ECM similar to human tissue for carrying various cells and biomolecules. Therefore, this study aimed to investigate the performance of these chitosan-based hydrogels for spinal cord regeneration in animal models. Electronic databases (Scopus, Web of Science, PubMed, and Google Scholar) were searched (March 2015 to April 2026) with main terms, including "Hydrogel," "chitosan," and "spinal cord" for every study that used biomolecules for the regeneration of spinal cord injury in animal models. The animal studies were selected according to the eligibility criteria and evaluated for risk of bias and quality assessment. After screening, 125 full-text articles were assessed for eligibility, and 54 studies were included in the qualitative synthesis. Chitosan-based hydrogels, alone or with polymers, biomolecules, and cells, were evaluated mainly in rat spinal cord injury models, with contusion most frequent. The Basso-Beattie-Bresnahan scale primarily assessed functional recovery, although most studies showed high or unclear risk of bias due to limited reporting. Chitosan-based hydrogels show promise for spinal cord regeneration, but variability in models and insufficient methodological reporting highlight the need for standardized protocols to enhance translation potential.Impact StatementSpinal cord injury is still a major clinical problem with few available treatments. In this systematic review, we summarize the evidence from 54 animal trials on the use of chitosan-based hydrogels for healing of spinal cord damage. The results show their biocompatibility, biodegradability, and ability to transfer biomolecules and cells, leading to functional recovery in preclinical animal models. However, methodological inconsistency and lack of reporting in research undermine the dependability of the translation. This study highlights the requirement for standardized experimental procedures and gives valuable knowledge to guide the future development and practical implementation of chitosan-based hydrogel treatments for spinal cord regeneration.