Effects of biodegradable polymer particles on rat marrow-derived stromal osteoblasts in vitro.

Effects of biodegradable particles of poly(L-lactic acid) (PLLA) and poly(DL-lactic-co-glycolic acid) (PLGA) 50/50 with diameter ranging from 1.0 to 1.5 microm on rat marrow stromal osteoblasts in vitro have been investigated over a period of 28 days. This study examined the effects of three particle parameters, concentration, polymer molecular weight, and composition, on osteoblast proliferation and function. Cell cultures were challenged with particles at two different time points: upon cell seeding (Day 1), and after cells had begun to establish their own mineralized extracellular matrix (Day 14). The most significant trend observed in those cultures challenged with particles beginning on Day 1 was due to increasing the concentration of particles, resulting in decreased [3H]-thymidine incorporation, cell count, and mineralization. Those cultures challenged with particles beginning on Day 14 were significantly more mineralized than those challenged with particles beginning on Day 1. In addition, increasing osteocalcin secretion confirmed the osteoblastic phenotype of the derived stromal cells. These studies suggest that the particles may affect the bone remodeling process surrounding a degrading implant by direct interaction with osteoblasts in addition to their indirect contributions to the inflammatory mechanism via mediators secreted by macrophages upon their phagocytosis.