Keratin Biomaterials Improve Functional Recovery in a Rat Spinal Cord Injury Model

Abstract

Study Design. Laboratory study using a rat T9 contusion model of spinal cord injury (SCI). Objective. The purpose of this study was to evaluate which method of delivery of soluble keratin biomaterials would best support functional restoration through the macrophage polarization paradigm. Summary of Background Data. SCI is a devastating neurologic event with complex pathophysiological mechanisms that currently has no cure. After injury, macrophages and resident microglia are key regulators of inflammation and tissue repair exhibiting phenotypic and functional plasticity. Keratin biomaterials have been demonstrated to influence macrophage polarization and promote the M2 anti-inflammatory phenotype that attenuates inflammatory responses. Methods. Anesthetized female Lewis rats were subjected to moderate T9 contusion SCI and randomly divided into: no therapy (control group), an intrathecally injected keratin group, and a keratin-soaked sponge group (n = 11 in all groups). Functional recovery assessments were obtained at 3- and 6-weeks post-injury (WPI) using gait analysis performed with the DigiGait Imaging System treadmill and at 1, 3, 7, 14, 21, 28, 35, and 42 days post-injury by the Basso, Beattie, Bresnahan (BBB) locomotor rating scale. Histology and immunohistochemistry of serial spinal cord sections were performed to assess injury severity and treatment efficacy. Results. Compared to control rats, applying keratin materials after injury improved functional recovery in certain gait parameters and overall trended toward significance in BBB scores; however, no significant differences were observed with tissue analysis between groups at 6 WPI. Conclusion. Results suggest that keratin biomaterials support some locomotor functional recovery and may alter the acute inflammatory response by inducing macrophage polarization following SCI. This therapy warrants further investigation into treatment of SCI. Level of Evidence: N/A

Bio-Scaffolds as Cell or Exosome Carriers for Nerve Injury Repair

“…Keratin/alginate scaffolds have been applied successfully for tissue regeneration in vitro [108]. Furthermore, keratin has been shown to promote Schwann cell proliferation in vitro and improve nerve regeneration in vivo [109,110] (Figures 3 and 4).…”

“…Promoted nerve regeneration and locomotor function [71] Abbreviations: PDGF-MS: platelet-derived growth factor-microsphere; MUSE-NPCs: neural progenitor cells differentiated in vitro from multilineage-differentiating stress-enduring cells. Improved functional recovery and inhibition of inflammatory response through macrophage polarization [110] Abbreviations: CSPG: chondroitin sulfate proteoglycans; VEGF: vascular endothelial growth factor; BDNF: brain-derived neurotrophic factor; MSCs: mesenchymal stem cells.…”