Devising micro/nano-architectures in multi-channel nerve conduits towards a pro-regenerative matrix for the repair of spinal cord injury

Abstract

Multi-channel nerve conduits have shown significant advantages in guidance of axonal growth and functional restoration after spinal cord injury (SCI). It was realized that the micro/nano-architectures of these implanted conduits can effectively tune the lesion-induced biological responses, including inflammation and scar formation. In this work, two PLLA multi-channel conduits were fabricated with ladder-like porous channel wall (labelled as LNCs) and nano-fibrous channel wall (labelled as NNCs), respectively, and transferred into complete spinal cord transected injury model in rats. The implantation of such two scaffolds significantly alleviated the infiltration of macrophages/microglia and accumulation of astrocyte and collagen scar, especially in the NNCs group. Meanwhile, recruitment of endogenous stem cells and axonal growth was observed in both of the multi-channel conduits. Compared to the LNCs, the extracellular matrix (ECM) – mimicry nanostructures in the NNCs promoted directional nerve fiber growth within the channels. Moreover, a relatively denser nano-architecture in the channel wall confined the nerve fiber extension within the channels. These results from in vivo evaluations suggested that the NNCs implants possess a great potential in future application for SCI treatment and nerve regeneration. Statements of SignificanceThe implantation of biocompatible and degradable polymeric scaffolds holds great potential in clinical treatment and tissue regeneration after spinal cord injury (SCI). In this work, the ladder-like nerve conduits (LNCs) and nano-fibrous nerve conduits (NNCs) were fabricated and implanted into completely spinal cord transected rats, respectively. In vivo characteristics showed significant reduction in post-injury inflammation and scar formation, with elevated nerve stem cells (NSCs) recruitment and nerve fiber growth, hence both conduits resulted in significant functional restoration after implantation. Remarkably, we noticed that not only the multi-channels in the conduits can guide nerve fiber regeneration, their micro-/nano-structured walls also played a critical role in modulating the post-implantation biological responses.