HYDROGELS CONTAINING PEPTIDE OR AMINOSUGAR SEQUENCES IMPLANTED INTO THE RAT-BRAIN - INFLUENCE ON CELLULAR MIGRATION AND AXONAL GROWTH

Biocompatible polymer matrices for implantation into lesion sites in t he brain were synthesized by incorporating peptide or aminosugar seque nces into N-(2-hydroxypropyl)methacrylamide (HPMA) hydrogels. RGD pept ide sequences were chemically linked to the hydrogel backbone via a gl ycylglycine spacer; aminosugars were glucosamine (NHGlc) or N-acetylgl ucosamine residues, Unmodified or sequence containing HPMA hydrogels w ere implanted into the lesioned optic tract or cerebral cortex of juve nile (17- to 19-day-old) or adult rat brains, respectively. After 10-1 2 months host animals were perfused and the brains were processed for immunohistochemistry using antibodies to neurofilaments (RT97), lamini n, glial fibrillary acidic protein (GFAP), carbonic anhydrase II (CAII ), S100 protein, macrophages (ED1), and myelin basic protein (MBP). Un modified (control) HPMA hydrogels contained no cellular infiltration o r axonal growth. Pep tide (RGD)- and aminosugar-modified hydrogels sho wed increased adhesion properties with host neural tissue, were vascul arized, and were in filtrated by host nonneuronal cells, Astrocytes (G FAP(+)) and macrophages (ED1(+)) were the major cell types seen within modified HPMA hydrogels, the largest numbers being found in RGD-conta ining polymers, CAII(+) oligodendroglia were not seen within any of th e hydrogel matrices, RT97(+)/MBP(-) axons grew into both the RGD and N HG1c hydrogel matrices for small distances. The number of axons was gr eatest in hydrogels implanted into cerebral cortex but in both cortex and optic tract implants the highest density of axons was seen in poly mers containing RGD. The findings of this study are discussed in the c ontext of CNS tissue replacement and the construction of bioactive sca ffolds to promote regenerative axonal growth across areas of injury in the brain and spinal cord. (C) 1997 Academic Press.