Impact of lactic acid on cell proliferation and free radical‐induced cell death in monolayer cultures of neural precursor cells

Abstract

Biomaterials prepared from polyesters of lactic acid and glycolic acid, or a mixture of the two, degrade in the presence of water into the naturally occurring metabolites, lactic acid and glycolic acid. While the lactic acid degradation product that is released from biomaterials is well-tolerated by the body, lactic acid can influence the metabolic function of cells; it can serve as an energy substrate for cells, and has been shown to have antioxidant properties. Neural precursor cells, a cell population of considerable interest as a source of cells for neural tissue regeneration strategies, generate a high amount of reactive oxygen species, and when associated with a degradable biomaterial, may be impacted by released lactic acid. In this work, the effect of lactic acid on a neural cell population containing proliferative neural precursor cells was examined in monolayer culture. Lactic acid was found to scavenge exogenously added free radicals produced in the presence of either hydrogen peroxide or a photoinitiator (I2959) commonly utilized in the preparation of photopolymerizable biomaterials. In addition to its effect on exogenously added free radicals, lactic acid reduced intracellular redox state, increased the proliferation of the cell population, and modified the cell composition. The findings of this study provide insight into the role that lactic acid plays naturally on developing neural cells and are also of interest to biomaterials scientists that are focused on the development of degradable lactic-acid based polymers for cell culture devices. The effect of lactic acid on other cell populations may differ and should be characterized to best understand how cells function in degradable cell culture devices.

Bioactive albumin functionalized polylactic acid membranes for improved biocompatibility

“…[4][5][6][7][8]). Although PLA has been approved for these applications [4,9], several studies have also shown that contact of some of the PLA based products with human body is associated with biocompatibility problems including inducing nodules and foreign-body granulomas [10] and post-implantation inflammation [11].…”

Control of Neural Cell Composition in Poly(Ethylene Glycol) Hydrogel Culture with Soluble Factors

“…Despite the initial neuronal loss, PEG hydrogels enrich the initial cell population for NPCs and maintain higher NPC percentages throughout the culture period relative to monolayers. The increased nestin levels in PEG hydrogels were similar to those observed in neurosphere culture, suggesting that any potentially mitogenic factors within the PEG hydrogel environment itself, such as reactive oxygen species 51 or lactic acid degradation products, 47 do not substantially contribute to nestin maintenance. It was also determined that aggregated growth is insufficient for increased nestin expression given the decreased nestin observed in agarose cultures.…”

“…While the mechanism of free-radical damage was not explored, a previous study proposed that Igacure 2959-generated free radicals may cause direct peroxidation of plasma membrane lipids. 47,48 Neurons may be particularly susceptible to free-radical damage given their lipid rich cellular membranes. 49 While maximizing the number of neurons present in PEG hydrogel culture is a priority for neuronal replacement therapies, efforts to rescue the fixed number of dissociated neurons may not be the most efficient approach to increase neuronal yields.…”

Engineering Biomaterials to Influence Oligodendroglial Growth, Maturation, and Myelin Production

“…Degradation can also confer advantages such as beneficial degradation products or controlled release of encapsulated molecules [Lampe et al, 2010a;Murphy et al, 2014;van Lith et al, 2014]. Polylactic acid, for instance, hydrolytically degrades releasing lactic acid, a normal metabolic product of glycolysis that may be beneficial to radical scavenging and cell protection [Lampe et al, 2009]. Controlled release, often through controlled degradation by combining polylactic acid with the faster degrading polyglycolic acid to form poly(lactic-co-glycolic acid) [PLGA], is also ideal because engineers can design materials which release molecules at a predetermined rate useful for cell survival or differentiation [Bible et al, 2009;Soderquist et al, 2010;Murphy et al, 2014].…”