3D collagen porous scaffold carrying PLGA-PTX/SDF-1α recruits and promotes neural stem cell differentiation for spinal cord injury repair

AbstractSpinal Cord Injury (SCI), one of the major factors of disability, can cause irreversible motor and sensory impairment. There are no effective therapeutic drugs and technologies available in domestic or foreign countries currently. Neural stem cells (NSCs), with the potential for multidirectional differentiation, are a potential treatment for SCI. However, it has been demonstrated that NSCs primarily differentiated into astrocytes rather than neurons due to the inflammatory microenvironment, and the current challenge remains to direct the differentiation of NSCs into neurons in the lesion site. It was reported that the microtubule-stabilizing agent paclitaxel (PTX) was able to promote the differentiation of NSCs into neurons rather than astrocytes after SCI. SDF-1α can recruit NSCs and thus guide the migration of stem cells. In this study, we developed a functional collagen scaffold by loading SDF-1α and nanoparticle-encapsulated PLGA-PTX into a 3D collagen porous scaffold, allowing for slow release of PTX. When the functional scaffolds were implanted into the injury site, it provided a neural regeneration conduit channel for the migration of NSCs and neuronal differentiation. Neural regeneration promoted the recovery of motor function and reduced glial scar formation after SCI. In conclusion, a 3D collagen porous scaffold combined with PLGA-PTX and SDF-1α is a promising therapeutic strategy for SCI repair.Keywords: Spinal cord injury3D collagen scaffoldNerve regenerationPaclitaxelSDF-1α AcknowledgementsWe would like to express gratitude to Professor Weiwei Zheng (The Affiliated Suzhou Hospital of Nanjing Medical University) by providing the professional instructions.Disclosure statementNo potential conflict of interest was reported by the authors.Authors contributionsYM (Doctor of Philosophy) was involved in study design, literature research, data analysis, and writing the manuscript. ZL (Master of Medicine), PX (Master of Medicine), LS (Master of Science) LF (Master of Medicine), HZ (Master of Medicine), BM (Master of Medicine), and YO (Bachelor's degree) were involved in the study design and data analysis.Data availability statementThe dataset used in this paper is available from the corresponding author upon request.Additional informationFundingThis study was supported by grants from the 512 Talents Development Project of Bengbu Medical College (by51202302), the Opening Project of Anhui Province Key Laboratory of Tissue Transplantation in Bengbu Medical College (AHTT2022A001), the Scientific Research Foundation of Bengbu Medical College (2021bypd006), and Graduate Student Research Innovation Program of Bengbu Medical College (Byycx21082, Byycx22092, and Byycx22126).