## 4 Discussion  
Bone regeneration constitutes an attractive therapeutic method for the customized treatment of bone defects following tooth extraction. The development of CAD/CAM technology can provide new options in this direction by manufacturing personalized scaffold patterns that precisely match the lesion. To the best of the authors' knowledge, this is the first systematic review aimed at evaluating the efficacy of 3D scaffolds in the bone regeneration of jaw defects in humans, ensuring adequate bone volume for dental implant placement. In this present review, we systematically evaluated only three human \begin{table}
\begin{tabular}{c c c c c c c c c} \hline \hline \multirow{2}{*}{**Author (Year)**} & **Random** & **Allocation** & **Blinding of** & **Binding of** & **Incomplete** & **Selective** & **Other Bias** & **Overall Bias** \\  & **Sequence** & **Concealment** & **Personnel** & **Assessment** & **Outcome Data** & **Reporting** & **Other Bias** & **Overall Bias** \\ \hline [PERSON] et al. & & & & & & & & & \\ (2014) [36] & + & + & – & – & + & + & + & – \\ \hline \hline \end{tabular}
\end{table} 
Table 4: Risk of bias of the included studies according to the revised Cochrane risk of bias assessment tool for randomized trials. \begin{table}
\begin{tabular}{l l l} \hline \hline
**Author (Year)** & **Type of 3D Scaffold** & **Adjunct** \\ \hline \hline \multirow{3}{*}{[PERSON] et al. (2013) [38]} & \multirow{3}{*}{\
\begin{tabular}{l} Porcine antigen-free \\ cartilage \\ \end{tabular} } & \multirow{3}{*}{
\begin{tabular}{l} Collagen-based \\ antigen-free \\ bovine bone \\ filling material \\ \end{tabular} } \\ \hline [PERSON] et al. (2014) [36] & PCL & - \\ \hline [PERSON] et al. (2014) [37] & Porous HA block & - \\ \hline \end{tabular} (3D): three-dimensional; (HA): hydroxyapatite; (PCL): polycaprolactone.  
\end{table} 
Table 3: Type of 3D scaffold and adjunct agents used for each included study. \begin{table}
\begin{tabular}{l l l l l l l l} \hline \hline
**Author (Year)** & **Random** & **Allocation** & **Blinding of** & **Binding of** & **Incomplete** & **Selective** & **Other Bias** & **Overall Bias** \\  & **Sequence** & **Concealment** & **Personnel** & **Assessment** & **Outcome Data** & **Reporting** & **Other Bias** & **Overall Bias** \\ \hline [PERSON] et al. & & & & & & & & \\ (2014) [36] & + & + & – & – & – & + & + & + & – \\ \hline \hline \end{tabular}
\end{table} 
Table 5: Risk of bias of the included studies according to the Newcastle-Ottawa Scale for non-randomized clinical trials. studies: one randomized clinical study, one case study, and one prospective study [36; 37; 38]. Due to the relatively recent nature of this therapeutic approach, there is a limited number of clinical studies on humans that meet the pre-established inclusion criteria. In total, our results revealed that 3D-printed scaffolds are easy to handle by clinicians, can fit precisely into the defect, contribute to uneventful healing, and generally yield better outcomes in terms of ridge preservation, bone augmentation, and implant stability. Unfortunately, we encountered a high degree of heterogeneity across all domains in the included studies, including experimental protocols, study designs, and the small sample size. Furthermore, variations within humans, influenced by factors such as age, gender, overall systemic health, and biomechanical constraints, contributed to the complexity of the data. The examination of the international literature reveals numerous published case reports on the utilization of customized CAD/CAM scaffolds for bone augmentation and dental implant placement. [PERSON] et al. (2020) [39] presented a clinical case involving severe anterior maxillary atrophy in a younger female patient. The treatment comprised a titanium mesh scaffold customized using computer-aided design/computer-aided manufacturing (CAD/CAM), simultaneous implant placement, and a fully digital workflow. After an uncomplicated 4-month healing period, a second-stage surgery removed the titanium mesh.