## 4 Discussion
The number of fibrocytes and fibroblasts increased on Day 7 and decreased on Day 14 for all groups, because the wound conditions have peak proliferation phases for re-epithelial and angiogenesis processes [65]. For example in the DAO group on Day 3 up to Day 7 number of fibrocyte increased (19.0 \(\pm\) 1.9; 25.0 \(\pm\) 1.9 cells/mm\({}^{2}\)) and decreased on Day 14 (17.0 \(\pm\) 1.4 cells/mm\({}^{2}\)) (Table 6). The same thing happened to the number of fibroblasts in the DAO group on Day 3 up to Day 7 increased (20.0 \(\pm\) 0.7; 38.0 \(\pm\) 3.3 cells/mm\({}^{2}\)) and decreased on Day 14 (23.0 \(\pm\) 0.7 cells/mm\({}^{2}\)) (Table 7). Macrophages perform cytokine and growth factor secretions in the wound area to induce fibroblast migration and proliferation, production of granulation tissues, transient extracellular matrix and angiogenesis in the healing process. Conditions of high blood-glucose levels lead to migration and fibrocyte proliferation disorders, fibroblasts and keratinocytes, resulting in decreased secretion of cytokine, growth factor and extracellular matrix [63]. This is evidence by the lower number of fibrocytes on Day 3 up to Day 14 in the diabetic control group (10.0 \(\pm\) 1.9; 11.0 \(\pm\) 2.8; 10.0 \(\pm\) 0.7 cells/mm\({}^{2}\)) compared to normal control group (21.0 \(\pm\) 0.9; 27.0 \(\pm\) 2.3; 20.0 \(\pm\) 0.2 cells/mm\({}^{2}\)). The same thing happened to the number of fibroblasts on Day 3 up to Day 14 in the diabetic control group (11.0 \(\pm\)2.6; 20.0 \(\pm\) 0.9; 14.0 \(\pm\) 1.2 cells/mm\({}^{2}\)) compared to normal control group (22.0 \(\pm\) 1.6; 41.0 \(\pm\) 2.4; 26.0 \(\pm\) 1.4 cells/mm\({}^{2}\)). Fibroblast proliferation induces collagen synthesis and macromolecular matrix for structural formation of connective tissues. Diabetes conditions increase the activity of macrophages thereby increasing the production of ROS/RNS and lowering collagen synthesis [66]. This is evidence by the lower collagen densities on Day 3 up to Day 14 in the diabetic control group (30.0 \(\pm\) 0.6; 35.0 \(\pm\) 0.1; 50.0 \(\pm\) 4.9%) compared to normal control group (56.0 \(\pm\) 4.3; 81.0 \(\pm\) 6.4; 86.0 \(\pm\) 1.9%) (Table 8). \begin{table}
\begin{tabular}{c c c c} \hline \hline \multirow{2}{*}{**Group Treatment**} & \multicolumn{3}{c}{**Fibrocytes (cells/mm\({}^{2}\))**} \\ \cline{2-4}  & **Day 3** & **Day 7** & **Day 14** \\ \hline Normal (NC) & 21.0 \(\pm\) 0.9 & 27.0 \(\pm\) 2.3 & 20.0 \(\pm\) 0.2 \\ Diabetic (DC) & 10.0 \(\pm\) 1.9 & 11.0 \(\pm\) 2.8 & 10.0 \(\pm\) 0.7 \\ Alginate ointment (DA) & 13.0 \(\pm\) 0.5 & 17.0 \(\pm\) 0.9 & 14.0 \(\pm\) 1.2 \\ Alginate–oka ointment (DAO) & 19.0 \(\pm\) 1.9 * & 25.0 \(\pm\) 1.9 ** & 17.0 \(\pm\) 1.4 * \\ \hline \hline \end{tabular}  
* Letter notation on the table shows the result of the statistical test (\(\alpha<\) 0.05). (*) and (**) notation shows insignificant differences with NC, but significant differences with DC.
* = 0.01 \(\leq\alpha<\) 0.05; *
* = \(\alpha\leq\) 0.01.  
\end{table} 
Table 6: Counts considering the mean and standard deviation of fibrocytes. \begin{table}
\begin{tabular}{c c c c} \hline \hline \multirow{2}{*}{**Group Treatment**} & \multicolumn{3}{c}{**Fibroblasts (cells/mm\({}^{2}\))**} \\ \cline{2-4}  & **Day 3** & **Day 7** & **Day 14** \\ \hline Normal (NC) & 22.0 \(\pm\) 1.6 & 41.0 \(\pm\) 2.4 & 26.0 \(\pm\) 1.4 \\ Diabetic (DC) & 11.0 \(\pm\)2.6 & 20.0 \(\pm\) 0.9 & 14.0 \(\pm\) 1.2 \\ Alginate ointment (DA) & 13.0 \(\pm\) 1.4 & 27.0 \(\pm\) 1.2 & 17.0 \(\pm\) 0.2 \\ Alginate–oka ointment (DAO) & 20.0 \(\pm\) 0.7 * & 38.0 \(\pm\) 3.3 ** & 23.0 \(\pm\) 0.7 * \\ \hline \hline \end{tabular}  
* Letter notation on the table shows the result of the statistical test (\(\alpha<\) 0.05). (*) and (**) notation shows insignificant differences with NC, but significant differences with DC.
* = 0.01 \(\leq\alpha<\) 0.05; *
* = \(\alpha\leq\) 0.01.  
\end{table} 
Table 7: Counts considering the mean and standard deviation of fibroblasts.