Implantation of collagen IV/poly(2-hydroxyethyl methacrylate) hydrogels containing Schwann cells into the lesioned rat optic tract

Abstract

Poly (2-hydroxyethylmethacrylate) (PolyHEMA) hydrogels, when combined with extracellular matrix molecules and infiltrated with cultured Schwann cells, have the capability to induce CNS axonal regrowth after injury. We have further investigated these PolyHEMA hydrogels and their potential to bridge CNS injury sites. Collagen IV-impregnated hydrogels containing Schwann cells were implanted into the lesioned optic tract in 14 rats. On examination 2-4 months later, there was good adherence between the implants and CNS tissue, and large numbers of viable Schwann cells (S100+, GFAP+, Laminin+, and LNGFR+) were seen within the hydrogel matrices. Immunohistochemical analysis showed that the collagen IV-impregnated PolyHEMA hydrogels preferentially supported the transplanted Schwann cells and not host glial cells such as astrocytes (GFAP+) or oligodendroglia (CAII+). Macrophages (ED1+) were also seen within the sponge structure. Eighty-three percent of the implanted hydrogels contained RT97+ axons within their trabecular networks. Regrowing axons were associated with the transplanted Schwann cells and not with the small number of infiltrating astrocytes. RT97+ axons were traced up to 510 microm from the nearest host neuropil. These axons were sometimes myelinated by the transplanted Schwann cells and expressed the peripheral myelin marker Po+. WGA/HRP-labeled retinal axons were seen within transplanted hydrogel sponges, with 40% of the cases growing for distances up to 350-450 microm within the polymer network. The data indicate that impregnating PolyHEMA sponges with collagen IV can modify the host glial reaction and support the survival of transplanted Schwann cells. This study thus provides new information on how biomaterials could be used to modify and bridge CNS injury sites.