Hydrogels containing peptide or aminosugar sequences implanted into the rat brain: Influence on cellular migration and axonal growth

Abstract

Biocompatible polymer matrices for implantation into lesion sites in the brain were synthesized by incorporating peptide or aminosugar sequences into N-(2-hydroxypropyl)methacrylamide (HPMA) hydrogels. RGD peptide sequences were chemically linked to the hydrogel backbone via a glycylglycine spacer; aminosugars were glucosamine (NHGlc) or N-acetylglucosamine residues. Unmodified or sequence containing HPMA hydrogels were implanted into the lesioned optic tract or cerebral cortex of juvenile (17- to 19-day-old) or adult rat brains, respectively. After 10-12 months host animals were perfused and the brains were processed for immunohistochemistry using antibodies to neurofilaments (RT97), laminin, glial fibrillary acidic protein (GFAP), carbonic anhydrase II (CAII), S100 protein, macrophages (ED1), and myelin basic protein (MBP). Unmodified (control) HPMA hydrogels contained no cellular infiltration or axonal growth. Peptide (RGD)- and aminosugar-modified hydrogels showed increased adhesion properties with host neural tissue, were vascularized, and were infiltrated by host nonneuronal cells. Astrocytes (GFAP+) and macrophages (ED1+) were the major cell types seen within modified HPMA hydrogels, the largest numbers being found in RGD-containing polymers. CAII+ oligodendroglia were not seen within any of the hydrogel matrices. RT97+/MBP- axons grew into both the RGD and NHGlc hydrogel matrices for small distances. The number of axons was greatest in hydrogels implanted into cerebral cortex but in both cortex and optic tract implants the highest density of axons was seen in polymers containing RGD. The findings of this study are discussed in the context of CNS tissue replacement and the construction of bioactive scaffolds to promote regenerative axonal growth across areas of injury in the brain and spinal cord.