Perfusion-Decellularized Goat Spinal Cord Scaffold Promotes Neuroregeneration and Functional Recovery in a Rat Model of Spinal Cord Injury.

Abstract

Spinal cord injury (SCI) causes permanent loss of motor and sensory functions, which is primarily caused by restricted regenerative capacity and inhibitory post-injury environment. Maintenance of extracellular matrix (ECM) architecture is essential to sustain endogenous repair processes. This study aims to prepare perfusion-decellularized goat spinal cord scaffold (dGSC) and assess its therapeutic potential, biocompatibility, and structural integrity in fostering neuroregeneration and functional recovery in complete SCI rat model. This study employed agitation and perfusion method to goat spinal cord (GSC) with several detergents, including sodium deoxycholate (SDC), Triton X-100, Tween 20 (T20), Tween 80, sodium dodecyl sulfate, and their combinations. Among all the combinations, the SDC&#x2009;+&#x2009;T20 perfusion method showed less DNA content, and protein retention thus validating its biocompatibility and ECM integrity. This optimized scaffold was used for transplantion in complete thoracic SCI to investigate its ability to promote neural regeneration. Functional recovery was evaluated based on BBB scores, actophotometer measurements, MRI, electrophysiology, histology, immunohistochemistry, tract tracing, and analysis of gene expression after 4&#x2009;weeks. The perfusion-decellularized scaffold had significantly less DNA (<&#x2009;50&#x2009;ng/mg; p&#x2009;<&#x2009;0.01), retained ECM ultrastructure, and had favorable mechanical characteristics. Animals that had scaffolds implanted in them had greatly improved motor function (p&#x2009;<&#x2009;0.001), less glial scarring (GFAP, p&#x2009;<&#x2009;0.01), neuronal survival (NeuN+, p&#x2009;<&#x2009;0.05), and angiogenic (CD31, VEGF; p&#x2009;<&#x2009;0.05) response. Retrograde tract tracing confirmed that axons bridge the lesion. These findings suggest that the perfusion-decellularized goat spinal cord scaffold has great promise for clinical translation use as a biological bridge to facilitate neuroregeneration and functional recovery post SCI.