The effect of d,l-β-hydroxybutyric acid on cell death and proliferation in L929 cells

As a prerequisite for tissue engineering applications, researchers must understand the effect on local cell types of the degradation products of biodegradable polymers. Polyhydroxybutyrate (PHB) has received special interest as an implant material, because it degrades to release a normal component of blood and tissue, D,L-β-hydroxybutyrate (HB). We report that HB (0.02 g/l) promoted cell proliferation in cultured L929 cells plated at high cell density (1×105 cells/well) but not lower cell densities. While HB did not affect cell cycle progression, it significantly inhibited cell death. HB treatment prevented necrosis, reducing cell membrane permeability 4 h following serum withdrawal from the medium, and for all subsequent time points. In summary, HB promotes proliferation of L929 cells in high-density cultures by preventing apoptotic and necrotic cell death. This property makes biodegradable polymers containing HB, such as PHBHHx, attractive candidates for tissue engineering applications, especially those requiring the regeneration of large numbers of cells.