Role of the cross-linking enzyme tissue transglutaminase in the biologicalrecognition of synthetic biodegradable polymers

The calcium-dependent cross-linking enzyme tissue transglutaminase (tTgase, type II) is a potential novel player at the cell surface, where its contri bution to cell adhesion and stabilization of the extracellular matrix is be coming increasingly recognized. We investigated whether tTgase enhances the biological recognition of poly (DL lactide co-glycolide) (PLG), poly (epsi lon -caprolactone) (PCL), and poly (L lactide) (PLA), biomaterials widely u sed in medical implants. Three cell-model systems consisting of human osteo blasts, endothelial cells (ECV-304), and Swiss 3T3 fibroblasts were utilize d, in which tTgase expression was modulated by gene transfer, and the abili ty of cells to spread on these polymers was quantified in relation to the a ltered level of expressed tTGase. Results show that over-expression of tTga se in human osteoblasts positively correlated with cell spreading on PLG, w hile no attachment and spreading was found on PCL and PLA. Antisense silenc ing of tTgase in the endothelial cells led to a marked reduction of cell sp reading on all polymers. The hydrophobic nature of PLC also appeared to fav or endothelial cell attachment. Spreading of Swiss 3T3 fibroblasts on these biomaterials was only slightly affected by increased expression of tTgase, although cell spreading on control glass was increased. We propose that th e consideration of tTgase-mediated bioactivity in novel biomaterials may im prove cell attachment and promote biocompatibility. (C) 2000 John Wiley & S ons, Inc.