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Traumatic brain injury (TBI), especially moderate or severe TBI, is one of the most devastating injuries to the nervous system, as the existing therapies for neurological defect repair have difficulty achieving satisfactory results. Neural stem cells (NSCs) therapy is a potentially effective treatment option, especially after specific genetic modifications and when used in combination with biomimetic biological scaffolds. In this study, tussah silk fibroin (TSF) scaffolds with interconnected nanofibrous structures were fabricated using a top-down method. We constructed the apelin-overexpressing NSCs that were cocultured with a TSF nanofiber scaffold (TSFNS) that simulated the extracellular matrix in vitro. To verify the therapeutic efficacy of engineered NSCs in vivo, we constructed TBI models and randomized the C57BL/6 mice into three groups: a control group, an NSC-ctrl group (transplantation of NSCs integrated on TSFNS), and an NSC-apelin group (transplantation of apelin-overexpressing NSCs integrated on TSFNS). The neurological functions of the model mice were evaluated in stages. Specimens were obtained 24 days after transplantation for immunohistochemistry, immunofluorescence, and western blot experiments, and statistical analysis was performed. The results showed that the combination of the TSFNS and apelin overexpression guided extension and elevated the proliferation and differentiation of NSCs both in vivo and in vitro. Moreover, the transplantation of TSFNS-NSCs-Apelin reduced lesion volume, enhanced angiogenesis, inhibited neuronal apoptosis, reduced blood-brain barrier damage, and mitigated neuroinflammation. In summary, TSFNS-NSC-Apelin therapy could build a microenvironment that is more conducive to neural repair to promote the recovery of injured neurological function. [ABSTRACT FROM AUTHOR]

Biomaterial and regenerative medical research has diversified and developed rapidly. A biological scaffold consisting of an extracellular matrix (ECM) functions not only as a supportive material but also as a regulator of cellular functions. Although decellularized scaffolds have been widely applied for the repair of non-central nervous system (CNS) tissues, their efficacy in the CNS has not been extensively investigated. In this report, we describe a dynamic decellularization protocol that combined intracardial perfusion and a series of treatments to effectively remove the cellular components from the cerebellum, which is a unique and relatively simple CNS structure. The resulting cerebellar scaffold retained neurosupportive proteins and growth factors and, when tested with neural stem cells (NSCs) in vitro, was found to be cytocompatible and to stimulate the proliferation and migration of these cells. NSCs that were cultured in vitro on the scaffold differentiated into neurons and astrocytes, as indicated by their expression of βIII-tubulin and glial fibrillary acidic protein (GFAP). Through subcutaneous and intracranial implantation experiments, this preliminary study demonstrated the in vivo biocompatibility of the cerebellar scaffold and indicated its potential for future applications. Thus, our study demonstrated that the cerebellar ECM scaffold provided tissue-specific advantages for regenerative medical applications. [ABSTRACT FROM AUTHOR]