Background: Spinal cord injury (SCI) is a serious injury with high mortality and disability rates, and there is no effective treatment at present. It has been reported that some treatments, such as drug intervention and stem cell transplantation have positive effects in promoting neurological recovery. Although those treatments are effective for nerve regeneration, many drawbacks, such as low stem cell survival rates and side effects caused by systemic medication, have limited their development. In recent years, injectable hydrogel materials have been widely used in tissue engineering due to their good biocompatibility, biodegradability, controllable properties, and low invasiveness. The treatment strategy of injectable hydrogels combined with stem cells or drugs has made some progress in SCI repair, showing the potential to overcome the drawbacks of traditional drugs and stem cell therapy. Methods: In this study, a novel injectable electroactive hydrogel (NGP) based on sodium hyaluronate oxide (SAO) and polyaniline-grafted gelatine (NH₂-Gel-PANI) was developed as a material in which to load neural stem cells (NSCs) and donepezil (DPL) to facilitate nerve regeneration after SCI. To evaluate the potential of the prepared NGP hydrogel in SCI repair applications, the surface morphology, self-repairing properties, electrical conductivity and cytocompatibility of the resulting hydrogel were analysed. Meanwhile, we evaluated the neural repair ability of NGP hydrogels loaded with DPL and NSCs using a rat model of spinal cord injury. Results: The NGP hydrogel has a suitable pore size, good biocompatibility, excellent conductivity, and injectable and self-repairing properties, and its degradation rate matches the repair cycle of spinal cord injury. In addition, DPL could be released continuously and slowly from the NGP hydrogel; thus, the NGP hydrogel could serve as an excellent carrier for drugs and cells. The results of in vitro cell experiments showed that the NGP hydrogel had good cytocompatibility and could significantly promote the neuronal differentiation and axon growth of NSCs, and loading the hydrogel with DPL could significantly enhance this effect. More importantly, the NGP hydrogel loaded with DPL showed a significant inhibitory effect on astrocytic differentiation of NSCs in vitro. Animal experiments showed that the combination of NGP hydrogel, DPL, and NSCs had the best therapeutic effect on the recovery of motor function and nerve conduction function in rats. NGP hydrogel loaded with NSCs and DPL not only significantly increased the myelin sheath area, number of new neurons and axon area but also minimized the area of the cystic cavity and glial scar and promoted neural circuit reconstruction. Conclusions: The DPL- and NSC-laden electroactive hydrogel developed in this study is an ideal biomaterial for the treatment of traumatic spinal cord injury.

The Primary cilium, a non-motile organelle, was long underestimated but has recently been recognized as a pivotal signaling platform in nervous system development. This review summarizes the structural features, biogenesis, and dynamic regulation of primary cilia, and systematically examines their roles in neural stem cells fate determination, neurogenesis, neuronal migration, axon guidance, and synaptogenesis. By integrating multiple developmental signaling pathways, including Sonic hedgehog, Wnt, Notch, and mTOR, primary cilia orchestrate the precise spatiotemporal patterning of the nervous system. Dysfunction of primary cilia is closely linked to a wide spectrum of neurodevelopmental disorders, ranging from classical ciliopathies such as Meckel-Gruber syndrome, Joubert syndrome, and Bardet-Biedl syndrome, to complex conditions such as autism spectrum disorder, schizophrenia, and bipolar disorder, all of which can be traced to ciliary signaling imbalances. This paper introduces the concept of the continuous spectrum of Ciliogenesis, in which phenotypes from severe structural malformations to subtle functional abnormalities can be attributed to defects in specific ciliary modules. Future interventions, including organoid models, super-resolution imaging, and cilia-targeted therapeutic strategies, hold promise for advancing pathological insights and developing novel treatments for neurodevelopmental disorders.

Nerve regeneration and axonal growth can be significantly enhanced by electrical stimulation (ES) using conductive polymers. But in addition to ES, nerve c

Background: The primary cilium (PC) is a pivotal organelle for neuronal signaling and development, while tau tubulin kinase 2 (TTBK2) is a key initiator of ciliogenesis. However, the role of TTBK2 in spinal neurons during spinal cord injury (SCI) and subsequent neural repair remains unclear. Methods: We manipulated TTBK2 expression in spinal neurons using adenovirus‐mediated overexpression and knockdown in vitro. Transcriptomic profiling (RNA‐sequencing) and RT‐qPCR were employed to explore the potential regulatory pathways at the molecular level. In vivo, Ttbk2 ^fl/fl ‐Rosa‐CreERT2 ^+/− conditional knockout mice were subjected to a spinal cord hemisection model. Behavioral assays, immunofluorescence, and biotinylated dextran amine (BDA) tracing were conducted to assess neuronal survival, axonal regeneration, and circuit reorganization. Results: Here, we demonstrated that intact activity of TTBK2 in PC promoted neural survival, axonal regeneration, and neural circuit remodeling. However, loss of TTBK2 impaired PC function and hindered recovery after SCI. Conclusions: These findings extend the role of PCs beyond neurodevelopment, demonstrating that the TTBK2–PC functions as an endogenous repair mechanism after SCI. Targeting this pathway may provide novel therapeutic strategies for enhancing neural regeneration.

Background Spinal cord injury (SCI) is a serious injury with high mortality and disability rates, and there is no effective treatment at present. It has been reported that some treatments have positive effects in promoting neurological recovery, such as drug intervention and stem cell transplantation. Although those treatments are effective for nerve regeneration, many drawbacks have limited their development, such as low stem cell survival rates and side effects caused by systemic medication. In recent years, injectable hydrogel materials have been widely used in tissue engineering due to their good biocompatibility, biodegradability, controllable properties, and low invasiveness. The treatment strategy of injectable hydrogels combined with stem cells or drugs has made some progress in SCI repair, which can overcome the defects existing in traditional drugs and stem cell therapy. Method In this study, a novel injectable electroactive hydrogel (NGP) based on sodium hyaluronate oxide (SAO) and polyaniline-grafted gelatin (NH₂-Gel-PANI) was developed to load neural stem cells (NSCs) and donepezil (DPL) to facilitate nerve regeneration post-SCI. To evaluate the potential of the prepared NGP hydrogel in SCI repair application, the surface morphology, self-repairing properties, electrical conductivity and cytocompatibility of the resulting hydrogel were analyzed. Meanwhile, we evaluated the neural repair ability of NGP hydrogels loaded with DPL and NSCs using a rat model of spinal cord injury. Result The NGP hydrogel has a suitable pore size, good biocompatibility, excellent conductivity, injectable and self-repairing properties, and its degradation rate matches the repair cycle of spinal cord injury. At the same time, DPL could be released continuously and slowly in the NGP hydrogel; thus, the NGP hydrogel could be used as an excellent carrier of drugs and cells. The results of in vitro cell experiments showed that the NGP hydrogel had good cytocompatibility and could significantly promote neuronal differentiation and axon growth of NSCs, and the hydrogel loaded with DPL could significantly enhance this effect. More importantly, the NGP hydrogel loaded with DPL showed a significant inhibitory effect on astrocyte differentiation of NSCs in vitro. Animal experiments show that the combination of NGP hydrogel + DPL + NSCs group showed the best therapeutic effect on the recovery of motor function and nerve conduction function in rats. NGP hydrogel-loaded NSCs and DPL not only significantly increased the myelin sheath area, number of new neurons and axon area but also minimized the area of the cystic cavity and glial scar and promoted neural circuit reconstruction. Conclusions The DPL and NSCs-laden electroactive hydrogel developed in this study is an ideal biomaterial for the treatment of traumatic spinal cord injury.