Virus‐Engineered Microsol Electrospun Scaffold Promotes the Reprogramming of Fibroblasts to Neurons

Abstract Lentiviral‐vector‐based therapies, widely used for treating various diseases, face limitations because of release burst, rapid clearance, and immune activation. Herein, a lentiviral vector delivery platform is proposed utilizing a virus‐engineered microsol electrospun scaffold. Identifying a remarkable upregulation of polypyrimidine tract binding protein1 (PTB) in spinal cord injury (SCI) rats, a scaffold is constructed comprising a hyaluronic acid (HA) core encapsulating brain‐derived neurotrophic factor (BDNF) and a polydopamine (PDA)‐modified linear poly‐l‐lactic acid (PLLA) shell, with shPTB lentiviral vectors (LV‐shPTB) grafted via PDA. In vitro, the LV‐shPTB achieves an infection efficiency of 70%, and the oriented scaffolds significantly reduce the expression of inflammatory factors, induce the reprogramming of fibroblasts into neurons, and sustain the release of BDNF for over 2 weeks. In vivo, the scaffolds provide physical support and neural guidance, as well as released BDNF and LV‐shPTB. LV‐shPTB delivery leads to the reprogramming of fibroblasts into neurons, and the sustained BDNF delivery maintains the neurons’ proliferation and growth, which further promotes the recovery of neurological function in SCI rats. These results demonstrate the potential application of virus‐engineered delivery platforms in SCI treatment and other medical fields.