A novel composite type I collagen scaffold with micropatterned porosity regulates the entrance of phagocytes in a severe model of spinal cord injury

Abstract

Traumatic spinal cord injury (SCI) is a damage to the spinal cord that results in loss or impaired motor and/or sensory function. SCI is a sudden and unexpected event characterized by high morbidity and mortality rate during both acute and chronic stages, and it can be devastating in human, social and economical terms. Despite significant progresses in the clinical management of SCI, there remain no effective treatments to improve neurological outcomes. Among experimental strategies, bioengineered scaffolds have the potential to support and guide injured axons contributing to neural repair. The major aim of this study was to investigate a novel composite type I collagen scaffold with micropatterned porosity in a rodent model of severe spinal cord injury. After segment resection of the thoracic spinal cord we implanted the scaffold in female Sprague-Dawley rats. Controls were injured without receiving implantation. Behavioral analysis of the locomotor performance was monitored up to 55 days postinjury. Two months after injury histopathological analysis were performed to evaluate the extent of scar and demyelination, the presence of connective tissue and axonal regrowth through the scaffold and to evaluate inflammatory cell infiltration at the injured site. We provided evidence that the new collagen scaffold was well integrated with the host tissue, slightly ameliorated locomotor function, and limited the robust recruitment of the inflammatory cells at the injury site during both the acute and chronic stage in spinal cord injured rats. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1040-1053, 2017.

Fibroadhesive scarring of grafted collagen scaffolds interferes with implant–host neural tissue integration and bridging in experimental spinal cord injury

“…The efficiency of such scaffolds to bridge injury sites critically depends on their ability to integrate with damaged host tissues [18, 19]. Amongst the wide range of natural polymers used for tissue engineering and regenerative medicine in nervous tissue repair (of both CNS and PNS), collagen has proven to be a popular choice ([35–40] also reviewed in [15]). A number of research groups have implanted micro-structured collagen scaffolds into complete transection or hemisection injuries of the adult rats spinal cord (with or without added pharmacological agents, neutralizing agents or seeding with axon growth-promoting cells) but have largely failed to demonstrate any substantial penetration of the scaffold by host astroglia or crossing of the scaffold by regenerating intrinsic CNS axons [18, 19, 31, 33, 37, 40].…”

Mimicking the Hierarchical Organization of Natural Collagen: Toward the Development of Ideal Scaffolding Material for Tissue Regeneration

“…Physical treatments that include ionizing, UV irradiation, dehydrothermal treatment (DHT), and dye-mediated photo-oxidation (Weadock et al, 1996;Gu et al, 2019) allow to achieve low values of crosslink density that restrict their range of application. Hence, a wide range of chemicals such as aldehydes (formaldehyde, glutaraldehyde, acrolein, glyoxal, malondialdehyde, succinaldehyde, dialdehyde starch), isocyanates (hexamethylene diisocyanate), carbodiimides [ethyl-3(3-dimethylamino)propylcarbodiimide], epoxides (1,4butanediol diglycidyl ether, ethylene glycol diglycidyl ether), and some natural agents extracted from plants (gallic acid, glucose, quinones, genipin, oleuropein) were investigated as crosslinking agents in order to enhance the residence time and the mechanical performances of collagen-based devices (Madaghiele et al, 2009;Salvatore et al, 2014Salvatore et al, , 2020cMadaghiele et al, 2016;Snider et al, 2017;Gallo et al, 2018;Terzi et al, 2018;Adamiak and Sionkowska, 2020;Gallo et al, 2020a). Recently, some enzymes such as tyrosinase, laccase, and mostly transglutaminase have also been investigated as non-toxic agents (Gu et al, 2019;Adamiak and Sionkowska, 2020).…”

Extracellular matrix remodeling in human disease

“…[ 43 ] The effect of collagen on axon growth is in collaboration with growth factors or repair-supporting cells. In injury, the inflammatory response can also be modulated by collagen,[ 44 ] which supports axon growth in scar tissue.…”