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We identified a suitable biomatrix that improved axon regeneration and functional outcome after partial (moderate) and complete (severe) chronic spinal cord injury (SCI) in rat. Five weeks after dorsal thoracic hemisection injury the lesion scar was resected via aspiration and the resulting cavity was filled with different biopolymers such as Matrigel™, alginate-hydrogel and polyethylene glycol 600 (PEG) all of which have not previously been used as sole graft-materials in chronic SCI. Immunohistological staining revealed marked differences between these compounds regarding axon regeneration, invasion/elongation of astrocytes, fibroblasts, endothelial and Schwann cells, revascularization, and collagen deposition. According to axon regeneration-supporting effects, the biopolymers could be ranked in the order PEG>>alginate-hydrogel>Matrigel™. Even after complete chronic transection, the PEG-bridge allowed long-distance axon regeneration through the grafted area and for, at least, 1cm beyond the lesion/graft border. As revealed by electron microscopy, bundles of regenerating axons within the matrix area received myelin ensheathment from Schwann cells. The beneficial effects of PEG-implantation into the resection-cavity were accompanied by long-lasting significant locomotor improvement over a period of 8months. Following complete spinal re-transection at the rostral border of the PEG-graft the locomotor recovery was aborted, suggesting a functional role of regenerated axons in the initial locomotor improvement. In conclusion, scar resection and subsequent implantation of PEG into the generated cavity leads to tissue recovery, axon regeneration, myelination and functional improvement that have not been achieved before in severe chronic SCI., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Abstract Complete transected spinal cord injury (SCI) severely influences the quality of life and mortality rates of animals and patients. In the past decade, many simple and combinatorial therapeutic treatments have been tested in improving locomotor function in animals with this extraordinarily challenging SCI. The potential mechanism for promotion of locomotor function relies either on direct motor axon regeneration through the lesion gap or indirect neuronal relay bridging to functionally reconnect transected spinal stumps. In this review, we first compare the advantages and problems of complete transection SCI animal models with other prevailing SCI models used in motor axon regeneration research. Next, we enumerate some of the popular bio-scaffolds utilized in complete SCI repair in the last decade. Then, the current state of motor axon regeneration as well as its role on locomotor improvement of animals after complete SCI is discussed. Last, the current approach of directing endogenous neuronal relays formation to achieve motor function recovery by well-designed functional bio-scaffolds implantation in complete transected SCI animals is reviewed. Although facilitating neuronal relays formation by bio-scaffolds implantation appears to be more practical and feasible than directing motor axon regeneration in promoting locomotor outcome in animals after complete SCI, there are still challenges in neuronal relays formation, maintaining and debugging for spinal cord regenerative repair. [ABSTRACT FROM AUTHOR]