A multi-modal delivery strategy for spinal cord regeneration using a composite hydrogel presenting biophysical and biochemical cues synergistically.

Abstract

Extensive tissue engineering studies have supported the enhanced spinal cord regeneration by implantable scaffolds loaded with bioactive cues. However, scaffolds with single-cue delivery showed unsatisfactory effects, most likely due to the complex nature of hostile niches in the lesion area. In this regard, strategies of multi-modal delivery of multiple heterogeneous cell-regulatory cues are unmet needs for enhancing spinal cord repair, which requires a thorough understanding of the regenerative niche associated with spinal cord injury. Here, by combining hierarchically aligned fibrin hydrogel (AFG) and functionalized self-assembling peptides (fSAP), a novel multifunctional nanofiber composite hydrogel AFG/fSAP characterized with interpenetrating network is designed. Serving as a source of both biophysical and biochemical cues, AFG/fSAP can facilitate spinal cord regeneration via guiding regenerated tissues, accelerating axonal regrowth and remyelination, and promoting angiogenesis. Giving the synergistic effect of multiple cues, AFG/fSAP implantation contributes to anatomical, electrophysiological, and motor functional restorations in rats with spinal cord hemisection. This study provides a novel multi-modal approach for regeneration in central nervous system, which has potentials for clinical practice of spinal cord injury.