Multiple Channel Bridges for Spinal Cord Injury: Cellular Characterization of Host Response

Abstract

Bridges for treatment of the injured spinal cord must stabilize the injury site to prevent secondary damage and create a permissive environment that promotes regeneration. The host response to the bridge is central to creating a permissive environment, as the cell types that respond to the injury have the potential to secrete both stimulatory and inhibitory factors. We investigated multiple channel bridges for spinal cord regeneration and correlated the bridge structure to cell infiltration and axonal elongation. Poly(lactide-co-glycolide) bridges were fabricated by a gas foaming=particulate leaching process. Channels within the bridge had diameters of 150 or 250 mm, and the main body of the bridge was highly porous with a controllable pore size. Upon implantation in a rat spinal cord hemisection site, cells infiltrated into the bridge pores and channels, with the pore size influencing the rate of infiltration. The pores had significant cell infiltration, including fibroblasts, macrophages, S-100b-positive cells, and endothelial cells. The channels of the bridge were completely infiltrated with cells, which had aligned axially, and consisted primarily of fibroblasts, S-100b-positive cells, and endothelial cells. Reactive astrocytes were observed primarily outside of the bridge, and staining for chondroitin sulfate proteoglycans was decreased in the region surrounding the bridge relative to studies without bridges. Neurofilament staining revealed a preferential growth of the neural fibers within the bridge channels relative to the pores. Multiple channel bridges capable of supporting cellular infiltration, creating a permissive environment, and directing the growth of neural fibers have potential for promoting and directing spinal cord regeneration.

Biomaterial bridges enable regeneration and re-entry of corticospinal tract axons into the caudal spinal cord after SCI: Association with recovery of forelimb function

“…A second biomaterials approach has sought to direct axonal growth through the damaged region of the spinal cord using 3D structured bridges that incorporate guidance conduits or channels [22-29]. In this regard, we have previously reported the development of porous, multi-channel poly(lactide-co- glycolide) (PLG) bridges in a rat thoracic SCI model [28-31]. In these studies, PLG bridges with linear channels and interconnected pores in vivo showed rapid ingrowth of cells and filled the space normally occupied by a cystic cavity, stabilizing the injury site.…”

Holistic Approach to Axonal Regeneration in Cases of Spinal Cord Injury

“…These tracts guide nerve sprouting and stimulate the formation of nerve bundles, which may in-turn benefit axonal regeneration [88]. It was discovered that the use of multiple channel bridges in the treatment of SCI can direct the growth of neural fibers and facilitate spinal cord regeneration.…”

Injectable Hydrogels for Spinal Cord Repair: A Focus on Swelling and Intraspinal Pressure

“…Studies in rodents have suggested that providing physical support via biomaterials in the acute phase after SCI may prevent cyst formation and reduce glial scar deposition [Prang et al, 2006;Yang et al, 2009b;Tuinstra et al, 2013b;Pawar et al, 2015b]. In the case of hydrogel biomaterials, this support may be provided by the mechanical strength or swelling pressure exerted on the surrounding tissue to hold the implant in position and form a tight interface with the host tissue.…”

“…Biomaterials that provide structural support and contain cell-scale macropores can prevent cyst formation and promote ample cell infiltration within the first few days of implantation, allowing a permissive interface between the biomaterial and the host spinal cord tissue [Yang et al, 2009b;Tuinstra et al, 2012;Thomas et al, 2013]. This early integration results in reduced glial scar deposition, which can allow more regenerating axons to enter, cross and exit the injury site via polymeric bridges [Tuinstra et al, 2012[Tuinstra et al, , 2013aPawar et al, 2015a].…”