[Effects and mechanism of tannic acid/magnesium nanocomplex on wound healing in rats with full-thickness scald].

Objective: To investigate the effects and mechanism of tannic acid/magnesium nanocomplex (MgTA NC) on wound healing in rats with full-thickness scald. Methods: This study was an experimental study. The MgTA NC with good biocompatibility was synthesized using the hydrothermal method. Mouse RAW 264.7 cells were divided into endotoxins/lipopolysaccharides (LPS) alone group, low MgTA NC group, medium MgTA NC group, and high MgTA NC group, which were all treated with LPS at final mass concentration of 1 μg/mL, and then cultured respectively with MgTA NC at the final mass concentration of 0 (without), 2.5, 5.0, or 7.5 μg/mL for 24 hours. The protein expressions of M1 type macrophage marker inducible nitric oxide synthase (iNOS), M2 type macrophage marker CD163, as well as glycolysis metabolism-related proteins pyruvate kinase type M2 (PKM2) and hexokinase in cells were detected by Western blotting; the expression levels of succinate dehydrogenase and isocitrate dehydrogenase in cells were detected by enzyme-linked immunosorbent assay method. The sample size in cell experiment was 3. Twelve six-week-old male Sprague-Dawley rats were selected and subjected to full-thickness scald on their backs using a temperature-controlled electrothermal burn device. The rats were assigned to control group, simple hydrogel group, and composite hydrogel group according to the random number table method, with 4 rats in each group. The wounds were treated with phosphate buffered saline, methacrylated gelatin (GelMA) hydrogel, or GelMA hydrogel loaded with MgTA NC, respectively. The wound healing rates were calculated at post-injury day 3, 7, and 14 (with the sample size of 4), and the expression level of inflammatory factor tumor necrosis factor α (TNF-α) in the wound tissue at post-injury day 14 was detected by immunohistochemical staining. Results: After 24 hours of culture, the protein expressions of iNOS, the M1 type macrophage marker in RAW 264.7 cells decreased successively in LPS alone group, low MgTA NC group, medium MgTA NC group, and high MgTA NC group, while the protein expressions of CD163, the M2 type macrophage marker increased successively, and the protein expressions of PKM2 and hexokinase decreased successively. After 24 hours of culture, compared with those in LPS alone group, the expression levels of succinate dehydrogenase and isocitrate dehydrogenase in RAW 264.7 cells in low MgTA NC group were significantly increased (P<0.05); compared with those in low MgTA NC group, the expression levels of succinate dehydrogenase and isocitrate dehydrogenase in RAW 264.7 cells in medium MgTA NC group were significantly increased (P<0.05); compared with those in medium MgTA NC group, the expression levels of succinate dehydrogenase and isocitrate dehydrogenase in RAW 264.7 cells in high MgTA NC group were significantly increased (P<0.05). At post-injury day 3, there was no statistically significant difference in the wound healing rate among the three groups of rats (P>0.05). At post-injury day 7 and 14, the wound healing rates of rats in simple hydrogel group were (52.28±5.11)% and (81.11±2.09)%, and those in composite hydrogel group were (76.81±2.68)% and (98.93±0.29)%, which were significantly higher than (32.75±6.86)% and (60.10±2.10)% in control group, respectively (P<0.05); the wound healing rates of rats in composite hydrogel group were significantly higher than those in simple hydrogel group (P<0.05). At post-injury day 14, the expression of TNF-α in the wound tissue of rats in simple hydrogel group and composite hydrogel group was significantly reduced compared with that in control group, and the expression of TNF-α in the wound tissue of rats in composite hydrogel group was significantly reduced compared with that in simple hydrogel group. Conclusions: MgTA NC exhibits excellent biocompatibility, and it is capable of modulating macrophage polarization toward the M2 type, effectively reducing glycolysis level and enhancing oxidative phosphorylation level of macrophages, suppressing excessive inflammatory responses and enhancing the ability of tissue regeneration and repair, therefore significantly accelerating wound healing in rats with full-thickness scald.