Trimethylene carbonate-caprolactone conduit with poly-p-dioxanone microfilaments to promote regeneration after spinal cord injury.

Abstract

Spinal cord injury (SCI) is often associated with scarring and cavity formation and therefore bridging strategies are essential to provide a physical substrate for axonal regeneration. In this study we investigated the effects of a biodegradable conduit made from trimethylene carbonate and ε-caprolactone (TC) containing poly-p-dioxanone microfilaments (PDO) with longitudinal grooves on regeneration after SCI in adult rats. In vitro studies demonstrated that different cell types including astrocytes, meningeal fibroblasts, Schwann cells and adult sensory dorsal root ganglia neurons can grow on the TC and PDO material. For in vivo experiments, the TC/PDO conduit was implanted into a small 2-3 mm long cavity in the C3-C4 cervical segments immediately after injury (acute SCI) or at 2-5 months after initial surgery (chronic SCI). At 8 weeks after implantation into acute SCI, numerous 5HT-positive descending raphaespinal axons and sensory CGRP-positive axons regenerated across the conduit and were often associated with PDO microfilaments and migrated host cells. Implantation into chronically injured SCI induced regeneration mainly of the sensory CGRP-positive axons. Although the conduit had no effect on the density of OX42-positive microglial cells when compared with SCI control, the activity of GFAP-positive astrocytes was reduced. The results suggest that a TC/PDO conduit can support axonal regeneration after acute and chronic SCI even without addition of exogenous glial or stem cells.

STATEMENT OF SIGNIFICANCE:

Biosynthetic conduits can support regeneration after spinal cord injury but often require addition of cell therapy and neurotrophic factors. This study demonstrates that biodegradable conduits made from trimethylene carbonate and ε-caprolactone with poly-p-dioxanone microfilaments alone can promote migration of different host cells and stimulate axonal regeneration after implantation into acute and chronic spinal cord injury. These results can be used to develop biosynthetic conduits for future clinical applications.

• Authors: Liudmila N Novikova, Mallappa K Kolar, Paul J Kingham, Andreas Ullrich, Sven Oberhoffner, Monika Renardy, Michael Doser, Erhard Müller, Mikael Wiberg, Lev N Novikov
• Journal: Acta biomaterialia (Acta Biomater) Vol. 66 Pg. 177-191 (01 15 2018) ISSN: 1878-7568 [Electronic] England
• PMID: 29174588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Biocompatible Materials
• Caproates
• Dioxanes
• Glial Fibrillary Acidic Protein
• Lactones
• Polymers
• poly-4-dioxan-2-one
• trimethylene carbonate
• caprolactone

Topics

• Animals
• Astrocytes (cytology, metabolism)
• Biocompatible Materials (chemistry)
• Caproates (chemistry)
• Cell Adhesion
• Dioxanes (chemistry)
• Female
• Fibroblasts (cytology, metabolism)
• Ganglia, Spinal (metabolism)
• Glial Fibrillary Acidic Protein (metabolism)
• Lactones (chemistry)
• Nerve Regeneration
• Neurites (metabolism)
• Polymers (chemistry)
• Rats, Sprague-Dawley
• Spinal Cord (pathology, physiopathology)
• Spinal Cord Injuries (physiopathology, therapy)
• Tissue Scaffolds (chemistry)