Neurales tissue engineering zur Unterstützung anatomischer und funktioneller Wiederherstellung nach akuter experimenteller Rückenmarksläsion der adulten Ratte

Injuries to the spinal cord induce distinct changes at the lesion site. Over recent years, it has been shown that the hostile environment of the reactive, lesioned central nervous system inhibits axonal regrowth. This is in stark contrast to the lesioned peripheral nervous system which has a strong capacity for axon regeneration and functional recovery. In the present thesis, a tissue engineering strategy to promote orientated axonal regrowth and functional tissue repair has been investigated in an experimental animal model of acute spinal cord injury. After undergoing a mid-cervical (C4) dorsal laminectomy, adult female Lewis rats were subjected to a unilateral funiculotomy (involving a tissue resection of 1 - 2 mm). A novel, orientated, type I collagen matrix (either seeded or non-seeded with syngeneic olfactory ensheathing cells, OEC) was implanted into the lesion gap and the function of the ipsilateral fore-paw was monitored. At the end-point survival time of 5 months, animals were perfused and the lesion site dissected and processed for immunohistochemistry to demonstrate host astrocystic, axonal and dendritic responses using antibodies to glial fibrillary acidic protein (GFAP), growth associated protein-43 (Gap-43/B50), 200kDa phosphorylated neurofilament (NF200) and microtubule associated protein 2 (MAP-2). The type I collagen matrix was found to be biocompatible and acted as a guidance system, supporting the longitudinally orientated regeneration of host axon Integration of the OEC-seeded matrix was most successful, with both host astrocytic and axonal profiles crossing the graft-host interface and penetrating the implant to varying degrees. Surprisingly, host dendrites were also found to penetrate the implanted matrices, a so-far undescribed phenomenon. Furthermore, the interface between the matrix and dura mater was found to be a region of substantial tissue regrowth and orientated axon regeneration. Although implanted scaffolds supported improved motor performance of the ipsilateral fore-paw, there was no clear correlation between the extent of axon regeneration and the degree of functional recovery. It is likely, therefore, that implanted devices may exert hitherto unexpected beneficial effects on the lesioned central nervous system