IN-VITRO CELL RESPONSE TO DIFFERENCES IN POLY-L-LACTIDE CRYSTALLINITY

Many different processing techniques are currently being used to produ ce tissue regeneration devices from polyesters in the polylactide/poly glycolide family. While it is generally well recognized that processin g techniques influence bulk mechanical and degradation properties of t hese materials, the effects on surface properties are relatively less well studied. We thus investigated the effects of processing condition s that are known to change bulk properties, but not composition, on th e surface properties of poly-L-lactide (PLLA). Specifically, we invest igated the role of bulk crystallinity of PLLA substrates on several ph ysicochemical aspects of the surface and on the attachment, morphology , and differentiated function of cultured primary hepatocytes and grow th of 3T3 fibroblasts. We fabricated smooth, clear PLLA films of 13-37 % crystallinity. Glancing angle X-ray diffraction indicated that low c rystallinity films lacked order in the first 50 A of the surface while relatively high crystallinity films had detectable order in this rang e. In other aspects, the surfaces of all PLLA substrates appeared iden tical with XPS, SEM, and advancing contact angle analysis, but contact angle hysteresis was slightly greater for more crystalline films. Alt hough the physicochemical properties of the surfaces appeared almost i dentical, we observed differences in cell behavior on less crystalline versus more crystalline films. Hepatocytes formed spheroids on all PL LA substrates, but spheroid formation was faster (24-48 h) on crystall ine substrates. Quantitative image analysis was used to assess the ave rage cell area as a function of time in culture, and our data confirm previous reports that retention of differentiated function is inversel y related to cell spreading where function was assessed by P450 enzyme activity. In addition, the growth rate of 3T3 fibroblasts was lower o n crystalline substrates than on amorphous substrates. An important co nclusion from this work is that processing techniques that lead to see mingly inconsequential changes in bulk and surface properties of these polymers may influence biological response. (C) 1996 John Wiley & Son s, Inc.