A new type of biocompatible bridging structure supports axon regrowth after implantation into the lesioned rat optic tract

We have developed a new type of polymer/cell/matrix implant and tested whet her it can promote the re growth of retinal ganglion cell (RGC) and other a xons across surgically induced tissue defects in the CNS. The constructs, w hich consisted of 2-2.5-mm-long polycarbonate tubes filled with lens capsul e-derived extracellular matrix coated with cultured neonatal Schwann cells, were implanted into lesion cavities made in the left optic tract (OT) of 1 8-21-day-old rats. In one group, to promote Schwann cell proliferation and perhaps also to stimulate axon regrowth, basic fibroblast growth factor (bF GF) was added to the lens capsule matrix prior to implantation. In another group, to determine whether application of growth factors to the somata of cells enhances the regrowth of distally injured axons, the neurotrophin NT- 4/5 was injected into the eye contralateral to the OT lesion. NT-4/5 and bF GF treatments were combined in some rats. After medium-term (4-10 weeks) or long-term (15-20 weeks) survivals, axon growth into implants was assessed immunohistochemically using a neurofilament (RT97) antibody. RGC axons were visualized after injection of WGA/HRP into the right eye. Viable Schwann c ells were present in implants at all times after transplantation. Large num bers of RT97(+) axone were consistently found within the bridging implants, often associated with the peripheral glia. Axons were traced up to 1.7 mm from the nearest CNS neuropil and there was immunohistochemical evidence of myelination by Schwann cells and by host oligodendrocytes. There were Fewe r RGC axons in the implants, fibers growing up to 1.6 mm from the thalamus. Neither NT-4/5 nor bFGF, alone or in combination, significantly increased the extent of RCC axon growth within the implants. A group of OT-lesioned r ats was implanted with polymer tubes filled with 2-2.5-mm-long pieces of pr edegenerate peripheral nerve. Surprisingly, polymer/cell/matrix constructs contained comparatively greater numbers of RGC and other axons and supporte d more extensive axon elongation. Thus, implants of this type may potential ly be useful in bridging large tissue defects in the CNS.