Thermosensitive hydrogel-mediated sphere/fiber multi-dimensional composite nanotube with controlled release of NGF for improved spinal cord injury repair

Abstract

Spinal cord injury is a serious disabling disease that not only causes physical defects, but also causes psychological problems for patients. In the current study, a novel multi-dimensional functional composite nanotube was prepared by simultaneouslyriveting nerve growth factor (NGF)-loaded PLGA microspheres and tissue-engineered cells (BMSCs) into the PLA fiber nanotube by a designed thermosensitive hydrogel to improve spinal cord injury (SCI) repair. The PLGA microspheres allow the protection and long-term controlled release of NGF to guarantee enough time and drug concentration to promote the growth and differentiation of cells into axons and promote axonal regeneration. Thermosensitive hydrogels are served not only to provide a tunable physiologically simulated microenvironment, but also as scaffolds to provide a suitable matrix for cells and drugs, and PLA nanotube ensures the seal of the released NGF in the nanotube to improve its drug bioavailability, as well as the supporting and guiding of the nerve growth. The physicochemical properties of the composite nanotube are investigated and the repair efficacy is evaluated according to the functional recovery, histological, immunohistochemistry, immunofluorescence examinations as well as the westernblot analysis. The administration of the composite nanotube in the SCI rat models obviously improves the regeneration of the neuron, axon, myelin sheath, neural stem cell and nissnei body but decreases the astrocytes formation, as well as enhances the integrity of the spinal cord tissue and the recovery of locomotor functions. This present work provides a future perspective for NGF application and a potential strategy for SCI repair.