Individualized bio-scaffold encapsulating siPTEN-loaded exosomes for promoting neuronal regeneration in spinal cord injury

Biological scaffold implants loaded with exosomes were acknowledged as a promising strategy for the treatment of spinal cord injury. In this study, we constructed an individualized biomimetic scaffold based on combination of multimodal imaging and 3D printing technology, featuring sustained release, biodegradability, and strongly biocompatibility. The scaffold incorporated mesenchymal stem cell-derived exosomes to alleviate inflammatory response in microenvironment and reduce scar formation of ECM molecule deposition. Furthermore, to effectively enhance neuronal repair and regeneration, siRNAs targeting PTEN were introduced into exosomes. The engineered exosomes within scaffold induced endogenous neuronal regeneration and enhanced axonal growth through PTEN/PI3K/AKT/mTOR signaling pathway. Additionally, implantation of scaffold could bridge the severed ends, thus providing spatial signals to modulate the organization of neural cells, facilitating the reconstruction of complex neural networks, and restoring nerve conduction. Collectively, the individualized 3D printed bio-scaffold encapsulated siPTEN-loaded exosomes could offer great promise for the prospective clinical translation in spinal cord injury therapy.