Macrophage/biomaterial interactions: The stimulation of endothelialization

Abstract

This current study analyzed macrophage/biomaterial interactions as modulators of endothelial cell proliferation. Rabbit peritoneal macrophages were harvested and seeded (1 x 10(6) cells/ml) into culture flasks with Dulbecco's modified Eagle medium and 10% platelet-poor, plasma-derived equine serum. Macrophages were identified by morphologic characteristics, nonspecific esterase, and Fc (immunoglobulin G) receptors on the cell membranes. Culture conditions were (1) no prosthetic material, (2) Dacron, or (3) Polyglactin 910 (PG910) (Ethicon, Inc., Somerville, N.J.). Both prosthetic materials were finely shredded into the media. After 5 weeks in culture, PG910 inclusions were seen within macrophage cytoplasm. No intracytoplasmic Dacron was observed. Conditioned media from all three groups were collected weekly from week 5 to week 10, centrifuged, filtered, and added in serial dilutions to cultured quiescent murine capillary lung endothelial cells. Quiescence was achieved by serum deprivation and verified by [3H]thymidine incorporation. Sixteen hours after addition of conditioned media, [3H]thymidine was measured in and expressed as percent increase above quiescent levels. Mitogenic activity in the PG910 group progressively increased from weeks 6 to 10. At week 10, the PG910 group (1:10 dilution) yielded a 620% increase in DNA synthesis. The Dacron group never varied from the control group (no prosthetic). The mean increases in [3H]thymidine incorporations over weeks 7 to 10 were PG910, 540% +/- 65%; Dacron, 323% +/- 65%, and control, 343% +/- 26% (PG910 vs Dacron, p less than or equal to 0.004). These studies suggest macrophage activation by bioresorbable prostheses, yielding growth factor release with subsequent enhanced endothelial cell proliferation.