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A novel, nontoxic, biodegradable, sponge-like polyurethane scaffold was synthesized from lysine-di-isocyanate (LDI) and glycerol. Ascorbic acid (AA) was copolymerized with LDI-glycerol. Our hypothesis was that the AA-containing polymer foam would enhance the biological activity of the osteoblastic precursor cell (OPCs). The LDI-glycerol-AA matrix degraded in aqueous solution to the nontoxic products of lysine, glycerol, and AA. The degradation products did not significantly affect the solution pH. The physical properties of the polymer network supported the cell growth in vitro. Mouse OPCs attached to the polymer matrix and remained viable. OPCs produced multilayered confluent cultures, a characteristic typical of bone cells. Furthermore, AA release stimulated cell proliferation, type I collagen, and alkaline phosphatase synthesis. Cells grown on the LDI-glycerol-AA matrix also showed an enhancement of mRNA expression for pro-alpha1 (I) collagen and transforming growth factor-alpha1 after 1 week. Data were tested for significance with an analysis of variance model and multiple comparison test (Fisher's Protected Least Significant Difference) at p < or = 0.05. The observations suggest that AA-containing polyurethane may be useful in bone tissue engineering applications.