Transected spinal cords grafted with in situ self-assembled collagen matrices

The purpose of this work was to evaluate if the implantation into the gap of a transected spinal cord of a biomaterial providing a scaffolding structure for tissue ingrowth would favor the permeation and the growth of regenerating axons across the spinal-bioimplant interface. The interstump gap of rat transected spinal cords was injected with an ice-cold neutral solution of collagen, either alone or mixed with glyoxal, a harmless tanning agent. Upon warming to the temperature of the tissue, the fluid implant self-assembled forming a loose fibrillar network which simultaneously re-established a physical continuity to the transected organ. At various post-implantation timepoints, the bioimplants were studied by light microscopy, with the picrosirius-polarization method and with scanning electron microscopy. We observed that the bioimplants evolved following three overlapping phases: first a massive inflammatory response characterized by the invasion of cells of heterogeneous nature, then, a phase where microcysts predominated and during which, there is a major remodeling of the biomatrix by the deposition of newly synthesized collagen and of a periodic acid Schiff-positive material. Finally, a regeneration phase occurred where astroglial processes followed by regenerating axons invaded the biomatrix. Three months after implantation, spinal axons had grown from the two spinal stumps and penetrated the bioimplant across at least one lesion interface. However, the glyoxal-tanned collagen matrices showed a better biostability and durability than collagen alone. We conclude that the histopathological reaction of the mammalian lesioned spinal cord, when adequately directed by a scaffolding structure can be beneficial for the expression of the intrinsic regenerative capacity of the spinal cord tissue.