RESUMEN
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 2-3â¯mm long cavity in the C3-C4 cervical segments immediately after injury (acute SCI) or at 2-5â¯months after initial surgery (chronic SCI). At 8â¯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.
Asunto(s)
Caproatos/química , Dioxanos/química , Lactonas/química , Regeneración Nerviosa , Polímeros/química , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/terapia , Animales , Astrocitos/citología , Astrocitos/metabolismo , Materiales Biocompatibles/química , Adhesión Celular , Femenino , Fibroblastos/citología , Fibroblastos/metabolismo , Ganglios Espinales/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Neuritas/metabolismo , Ratas Sprague-Dawley , Médula Espinal/patología , Médula Espinal/fisiopatología , Andamios del Tejido/químicaRESUMEN
A micro-structured, biodegradable, semipermeable hollow nerve guide implant was developed to bridge nerve lesions. Quantitative comparison of cell migration and axonal growth using time lapse video recording in vitro revealed that axons grow eight times faster than neuritotrophic Schwann cells migrate. To accelerate regeneration, purified Schwann cells are best injected into nerve guides before implantation. Nerve guides made from resorbable poly-lactide-co-glycolide support Schwann cell attachment, cell survival, and axonal outgrowth in vitro. The therapeutic concept aims at the development of an 'intelligent neuroprosthesis' that first mediates regeneration and then disappears.