Metabolic adaptation of human osteoblasts to growth on non-poled and poled-PLLA films


Poly (L-lactic) acid (PLLA) has shown great potential for bone tissue engineering because of its high biocompatibility and biodegradability. Furthermore, PLLA exhibits piezoelectric properties, at a comparable scale as the bone natural polymer, collagen, and believed to be able to modify cell behavior. The analysis of the metabolome of biological systems provides substantial information on metabolic changes triggered by key cellular events during cell/biomaterial interaction. To our knowledge, this the first NMR-based metabolomic study regarding the metabolic adaptation of human osteoblast cell line (HOb) in contact with non-poled and negatively-poled PLLA films. An untargeted metabolomic strategy was employed to characterize the metabolome of lysed HOb cells and cell extracts in the presence of non-poled or negatively poled PLLA, compared to the absence of polymer. Multivariate analysis unveiled that PLLA-grown cells are subjected to enhanced oxidative stress and activate energy metabolism at the cost of storage lipids and glucose. Some evidence of changes in protein and nucleic acid metabolisms was also noted, as was enhanced membrane biosynthesis. Analysis of aqueous extracts NMR spectra demonstrated that, compared to plastic, PLLA-exposed cells showed enhanced use of choline compounds, creatine, glutamate and hypoxanthine, with more marked variations for non-poled PLLA than for negatively poled-PLLA. Regarding lipophilic extracts, only a decrease in fatty acid methyls was noted, with no further changes in other lipid environments or average FA chain length and unsaturation degree. These results enabled small but clear metabolic effects of the presence of PLLA (either non-poled or negatively-poled) on HOb cells to be identified and suggest that poled PLLA is more efficient in sustaining cell growth than non-poled PLLA.


Araújo R, Carneiro T, Marinho P, Maltez da Costa M, Roque A, Cruz e Silva OAB, Fernandes MH, Vilarinho PM, Gil AM

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