## 4 Discussion
\begin{table}
\begin{tabular}{c c c c c} \hline \hline \multirow{2}{*}{**Time**} & \multirow{2}{*}{**Material**} & **Sterile** & **Non-Sterile** & \multirow{2}{*}{**\(t\)-Test \(p\)-Value**} \\ \cline{3-4}  & & **Mean \(\pm\) SD** & **Mean \(\pm\) SD** & \\ \hline \multirow{3}{*}{Day 1} & M & 5.57 \(\pm\) 0.14 & 5.33 \(\pm\) 0.18 & 0.15 \\ \cline{2-4}  & MP & 6.80 \(\pm\) 1.16 & 5.77 \(\pm\) 0.20 & 0.26 \\ \cline{2-4}  & MC & 5.82 \(\pm\) 0.56 & 5.75 \(\pm\) 0.43 & 0.86 \\ \hline \multirow{3}{*}{Day 3} & M & 55.50 \(\pm\) 1.55 & 51.10 \(\pm\) 1.47 & 0.02 * \\ \cline{2-4}  & MP & 73.59 \(\pm\) 1.75 & 62.07 \(\pm\) 0.29 & 0.01 * \\ \cline{2-4}  & MC & 64.81 \(\pm\) 0.60 & 62.17 \(\pm\) 1.53 & 0.05 \\ \hline \multirow{3}{*}{Day 7} & M & 163.81 \(\pm\) 1.06 & 165.07 \(\pm\) 1.77 & 0.35 \\ \cline{2-4}  & MP & 205.53 \(\pm\) 1.95 & 191.55 \(\pm\) 0.93 & 0.00 * \\ \cline{1-1} \cline{2-4}  & MC & 218.86 \(\pm\) 1.67 & 217.23 \(\pm\) 1.92 & 0.33 \\ \hline \hline \end{tabular}
* Statistically significant at \(p\leq\) 0.05.  
\end{table} 
Table 3: Comparison between sterile and non-sterile materials. The minimal increase in the overall drug release of the cobalt 60 irradiated group can be rationalized by the possible negative irradiation effect on the performance of drug delivery systems. Irradiation dosage is one of the most important factors because irradiation may generate certain unwanted physical and chemical alterations, especially when the dosage is delivered at the conventional 25 kGy threshold. The covalent bonds may break up owing to their ionizing nature. Therefore, the applied dosage must be handled with caution [40; 41; 42]. No burst release effect was observed on day 1 in both the sterile and non-sterile groups, in accordance with previous studies whose authors stated this might be due to the ability of antibiotics to hinder this phenomenon as well as the effect of the neutral pH environment used in this in vitro study to simulate the clinical implementation of titanium plates directly planted in the facial bone and its surrounding tissues with neutral pH [43]. On day 3, MP in the sterile group had the highest release compared to MC and M alone, while in the non-sterile group both MP and MC had similar release that was higher than M alone. On day 7, MP in the sterile group had a higher release than MC and M, while the non-sterile group MP and MC showed similar, statistically nonsignificant release. This is attributable to the PLGA being more prone to the negative sterilization effects of gamma irradiation, while all the other variables are constant (temperature, pH, and dissolving liquid) [44]. Local administration of antibiotics at the titanium plate site could be a practical approach for combating biofilms that has several benefits, such as high local effectiveness that can be reached at the targeted location. Moreover, the local administration of antibiotics permits targeting specific microorganisms, reducing antibiotic resistance. In vitro sustained release of antibiotics has been achieved by applying various surface coatings. Certain specifications involve both antibiotics and coating materials. Regarding antibiotics, a broad antibacterial spectrum and thermostability are the most crucial characteristics [18; 45]. In conclusion, the direct deposition of an antimicrobial material onto a plate's surface prevents bacterial colonization and enables the targeted release of a therapeutic agent to prevent or treat an infection. If a biofilm develops on the plate's surface, the therapeutic agent's presence at the plate site can immediately increase the treatment's efficacy. In addition, this local administration method can minimize the systemic adverse effects by decreasing the antibacterial agent dosage. No titanium plates for crani maxillofacial usage with antibacterial qualities are currently available on the market.