ackground: Spinal cord injury (SCI) is one of the long-term neurological deficits with primary and secondary damages. Various treatment strategies have not been successful in SCI treatment. The aim of this study was to design a platform containing a scaffold, an anti-inflammatory nanostructured drug, and stem cells for SCI treatment. Methods: For this aim, a fibrous composite scaffold of polyurethane/alginate was prepared using the electrospinning method. The hot homogenization method was utilized to encapsulate curcumin as an anti-inflammatory drug in the nanostructured lipid carrier (NLC). NLCs were coated with chitosan polymer (CS) in a core−shell structure for better attachment to the scaffold’s surface. The scaffold was covered with CS-coated NLCs and adipose-derived mesenchymal stem cells (ADMSC). The final platform was placed in the female Wistar rat model with spinal cord injury, and the therapeutic and anti- inflammatory effects at the lesion site, as well as behavioral analysis of rats, were investigated. Results: Results confirmed successful formation of the platform with proper attachment of the cells to the scaffold surface and more cell proliferation. Spreading the cells on the scaffold confirmed this scaffold as a good extracellular matrix. The efficacy of this platform in an in vivo environment showed the successful improvement of SCI in rats by increasing the myelin formation and decreasing the malondialdehyde. Results confirmed that lipid carriers reduced inflammatory factors; when combined with stem cell therapy, curcumin has demonstrated synergistic effects in enhancing functional recovery from severe SCI. Conclusions: Due to suitable biodegradability, biocompatibility, robustness, and cell growth of this platform, it is proposed for SCI treatment. A clinical assay could potentially be applied for this platform trial in the future.

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