This study proposes a strategy to promote the integration of a neural graft into the host brain tissue. It involves the attachment of donor cells to a polymeric matrix, and the implantation of this cell-polymer matrix. We have synthesized hydrogels based on N-(2-hydroxypropyl)-methacrylamide (HPMA) to produce highly porous matrices. As preliminary steps, we have examined: 1) The response of the brain tissue to the implantation of PHPMA/collagen hydrogels; 2) adhesion, growth, differentiation, and viability of embryonic neuronal cells, and embryonal carcinoma-derived neurons seeded onto PHPMA substrates containing hexosamine residues (glucosamine and N-acetylglucosamine), and after entrapment of cells within the hydrogels. Histological analysis seven wk after implantation showed the tolerance of PHPMA hydrogels, and the penetration of host cells into the pore structures. However, cellular ingrowth requires the presence of collagen, and is dependent upon porosity. In vitro data showed that PHPMA substrates supported neuronal cell attachment and neuritic growth, but the biocompatibility of the substrate was enhanced after incorporation of N-acetylglucosamine into the hydrogel. The data also showed the feasibility of entrapping cells into the polymer matrices, and that these "cellular" hydrogel matrices could be maintained in vitro with preservation of cell viability and differentiation. These findings suggest that PHPMA-based hydrogels can serve as carriers for neural transplant, and as a support to guide tissue ingrowth and organization.