Taxol-modified collagen scaffold implantation promotes functional recovery after long-distance spinal cord complete transection in canines

Abstract

Treatment of spinal cord injury (SCI) remains a clinical challenge worldwide because of the complicated inhibitory microenvironment formed post-injury, reduced axonal regenerative ability of spinal cord neurons, and scarcity of endogenous neurogenesis within the lesion center. Taxol, in addition to stabilizing microtubules, has shown potential for decreasing axonal degeneration and reducing scar formation after SCI in rodents. In this study, we further verified the therapeutic effects and clinical potential of Taxol on restriction of scar formation and promotion of neuronal regeneration and functional recovery after severe spinal cord transection in a large animal (canine) model. A linear-ordered collagen scaffold (LOCS) combined with Taxol was implanted into the injury site after the complete removal of 1 cm of spinal tissue. Afterwards, diligent nursing and multi-system rehabilitation were carried out during a half-year period of observation. The results showed that LOCS + Taxol implantation markedly promoted motor-evoked potentials and locomotion recovery. Moreover, histological analysis demonstrated that LOCS + Taxol implantation significantly increased neurogenesis and axon regeneration to reconnect the spinal cord stumps. Additionally, reduced glial scar formation was observed within the lesion site. Thus, LOCS + Taxol implantation treatment is a promising combinatorial therapy for the treatment of acute long-distance spinal cord defects.

Knockdown of Fidgetin Improves Regeneration of Injured Axons by a Microtubule-Based Mechanism

“…Epothilones act similarly but are preferred because they cross the blood-brain barrier (Ruschel et al, 2015). In a plethora of studies published over the past several years, microtubule-stabilizing drugs have been shown to augment nerve regeneration in the culture dish as well as animal models, even leading to partial recovery of function in rats with injured spinal cords (Hellal et al, 2011;Sengottuvel et al, 2011;Ruschel et al, 2015;Li et al, 2017;Ruschel and Bradke, 2018;Sandner et al, 2018;Yang et al, 2018;Yin et al, 2018). However, an independent attempt failed to achieve notable regeneration or functional recovery, with only modest improvements apparently attributable to the effects of the drugs on non-neuronal cells contributing to the glial scar (Popovich et al, 2014).…”

Development of Biocompatible and Antibacterial Collagen Hydrogels via Dialdehyde Polysaccharide Modification and Tetracycline Hydrochloride Loading

“…However, collagen hydrogels from skin or tendons usually suffer from poor mechanical strength and resistance to enzymatic degradation due to the relatively weak physical cross‐linking during hydrogel preparation. Hence, collagen hydrogels are often modified by various methods, for instance, dehydrothermal treatment (DHT), ultraviolet irradiation (UV), plasma modification, glutaraldehyde modification and 1‐ethyl‐3‐(3‐dimethyl aminopropyl) carbodiimide (EDC) . However, the treatment with UV or plasma only modifies the surface of collagen, DHT or EDC treatment plays a limited role in promoting the cross‐linking density, and the toxic nature of aldehyde compounds in glutaraldehyde prohibits its application in the process of preparing collagen‐based biomaterials .…”

Local Delivery of Taxol From FGL-Functionalized Self-Assembling Peptide Nanofiber Scaffold Promotes Recovery After Spinal Cord Injury

“…Previous methods of Taxol administration for SCI therapy include osmotic minipumps (PerezEspejo et al, 1996) and modified collagen scaffolds (Fan et al, 2018;Yin et al, 2018). In our study, we devised the FGL-functionalized SAP nanofiber scaffold, i.e., FGLmx, for Taxol administration.…”

“…Taxol, an FDA-approved anticancer drug, alters microtubule acetylation and promotes microtubule stabilization (Prota et al, 2013). Taxol remarkably increases axonal growth after SCI and protects cultured neurons from axonal retraction following axotomy (Baas et al, 2016;Fan et al, 2018;Yin et al, 2018). Moreover, Taxol also restores the axonal growth potential in the presence of inhibitory molecules (e.g., Nogo-A and CSPGs) (Sengottuvel et al, 2011).…”