Figure 9.

The synergistic and complementary functionalities of vitamin C in in vitro MI replica on fibrillar collagen formation becomes evident at the later incubation time point. In normal conditions, primary cardiac fibroblasts regulate naturally the internal ROS formation to low levels, which are relevant for optimal functionality of cells. The radical scavenger role of vitamin C is highly potentiated over time at the level of the oxidative protection of primary cardiac fibroblasts activation under normal conditions. The synergistic activity of vitamin C and coating composition is clearly visible through the massive upregulation of col5a1 mRNA and downregulation of ROS under profibrotic vs. normal settings. The increase expression of col5a1 mRNA translates into structurally stable type I and III collagen fibers, which is a process that is mainly potentiated by (i) fibronectin–collagen mixture coating in normal settings and (ii) fibronectin and collagen coatings, respectively, in profibrotic conditions. Altogether, optimum supplementation doses of cell media with vitamin C are required to prove its radical scavenging activity and gene and protein stabilizer/modulator role for the synthesis of structurally and compositionally stable collagen fibrils.