The modulation of corneal keratocyte and epithelial cell responses to poly(2-hydroxyethyl methacrylate) hydrogel surfaces: phosphorylation decreases collagenase production in vitro

We examined the regulation of collagenase production by rabbit keratocyte, epithelial and mixed keratocyte/epithelial cell cultures which were exposed to poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogel surfaces with differ ent chemistries and morphologies (sponge and homogeneous gels). Tissue cult ure modified polystyrene (TCP), used as a control surface, induced the maxi mum collagenase response with all cell culture types. Copolymer homogeneous gels containing 2-ethoxyethyl methacrylate (EEMA) or methyl methacrylate ( MMA) induced a high response in keratocyte cultures, whilst PHEMA hydrogels induced a moderate response and the phosphorylated PHEMA (phos-PHEMA) hydr ogel induced no response. Epithelial cells cultured on PHEMA, copolymer and phos-PHEMA hydrogels produced less collagenase activity than the keratocyt e cells. The profile of collagenases produced by epithelial cells in respon se to phos-PHEMA was different to that for the other hydrogels. Go-cultured cells produced higher levels of collagenase (relative to the TCP) in respo nse to hydrogels than did either the keratocytes or epithelial cells alone, but the response of phos-PHEMA was still the lowest. The overall enzyme re sponse to the sponge hydrogels was lower than that to the homogeneous hydro gels, although this effect was less prominent in the keratocyte cultures. T he markedly reduced and alternative collagenase responses to phosphorylated surfaces was not a consequence of cell death, and may be a phenomenon rela ted to changes in cell surface charge and morphology. (C) 1999 Elsevier Sci ence Ltd. All rights reserved.