Microchannel-containing hydrogel scaffolds enabled functional recovery in the absence of cells and bioactive molecules following spinal cord injury

Abstract

There is a lack of functional neural tissue regeneration following spinal cord injuries (SCIs) due to the resulting hostile microenvironment, necessitating interventional strategies such as tissue engineering scaffold implantation to promote neuronal regrowth within the lesion cavity. However, even in the presence of cells and/or bioactive molecules, the resulting neuronal regrowth has not necessarily led to functional recovery. This study leverages digital light processing (DLP) 3D-printing to create microchannel-containing hydrogel scaffolds towards imparting precise topographical cues for spinal cord tissue regeneration, focusing on facilitating unidirectional axonal bridging across lesion sites. Here, we optimized a gelatin methacryloyl and polyethylene glycol diacrylate (GelMA–PEGDA) composite hydrogel scaffold for printability and mechanical properties, aligning with native spinal cord characteristics whilst maintaining structural integrity during degradation. In vitro primary cell assays confirmed the scaffold's cytocompatibility and support for neuronal regeneration. In vivo assessments using a rat spinal cord complete transection model showed that, in the absence of cells or bioactive molecules, the microchannel-containing scaffolds enabled neurite ingrowth and promoted functional recovery of the hindlimbs over the 3-month implantation period. While the formation of cystic cavities was evident at the longer timepoints, the scaffolds did not induce strong glial scarring or inflammation. These findings provide strong preliminary data that suggests the 3D-printed GelMA–PEGDA scaffolds possessed suitable topographical cues, mechanical and biological properties that can support neuron infiltration into the lesion gap and trigger functional recovery. Together, these results show microchannel-containing hydrogel scaffolds have potential as a platform for neural regeneration post-spinal cord injury. More importantly, we provide evidence that with the appropriate materials and topographical cues alone, neural tissue regeneration and functional recovery can be induced without the need for cells or bioactive molecules.