Investigation of the biphasic effect of lithium ions on HUVEC proliferation in bioactive glass extracts for burn wound regeneration

In the current work, we developed a simplified empirical formula to isolate and define the effect of lithium ions (Li+) released from Li-BG on the proliferation of human umbilical vein endothelial cells (HUVECs), based on experiments by Wei et al. We incorporate both culture time and concentration of Li+ (۰–۶۵.۴ ppm), while providing a hormesis term to partition the characteristic biphasic (bell-shaped) cellular response to lithium. Nonlinear regression to discover best-fit parameters resulted in R۲ = ۰.۸۷۰۷ and RMSE = ۰.۰۴۰۴. Models predict maximum stimulatory effects would occur at ~۱۵ ppm Li+, which corresponds with our in vitro results that enhanced HUVEC viability occurred at ۱/۸–۱/۱۶ dilutions of ۲.۵Li-BG and ۳.۷۵ Li-BG nanostructured glasses. Additionally, Monte Carlo simulation determined, for the probability of desired cellular outcomes (>۸۰% probability HUVEC OD۴۵۰ > ۰.۳), there exists a therapeutic window (۱۰–۱۵ ppm) with maximum likelihood of achieving desired cellular consequences for probabilistic models. Although the full bioactivity of Li-BG is derived from the combined expression of Li+ and Si۴+ ions, as demonstrated in the original experimentation, this framework focused exclusively on Li+ allows some predictive modeling to optimize subsequent ion release profiles for next-generation wound dressings.In the current work, we developed a simplified empirical formula to isolate and define the effect of lithium ions (Li+) released from Li-BG on the proliferation of human umbilical vein endothelial cells (HUVECs), based on experiments by Wei et al. We incorporate both culture time and concentration of Li+ (۰–۶۵.۴ ppm), while providing a hormesis term to partition the characteristic biphasic (bell-shaped) cellular response to lithium. Nonlinear regression to discover best-fit parameters resulted in R۲ = ۰.۸۷۰۷ and RMSE = ۰.۰۴۰۴. Models predict maximum stimulatory effects would occur at ~۱۵ ppm Li+, which corresponds with our in vitro results that enhanced HUVEC viability occurred at ۱/۸–۱/۱۶ dilutions of ۲.۵Li-BG and ۳.۷۵ Li-BG nanostructured glasses. Additionally, Monte Carlo simulation determined, for the probability of desired cellular outcomes (>۸۰% probability HUVEC OD۴۵۰ > ۰.۳), there exists a therapeutic window (۱۰–۱۵ ppm) with maximum likelihood of achieving desired cellular consequences for probabilistic models. Although the full bioactivity of Li-BG is derived from the combined expression of Li+ and Si۴+ ions, as demonstrated in the original experimentation, this framework focused exclusively on Li+ allows some predictive modeling to optimize subsequent ion release profiles for next-generation wound dressings.