The present technique for the fabrication of customized allogeneic bone grafts for maxillary ridge reconstruction can provide different benefits for the patient and for the clinician. In fact, the accurate reproduction of the patient’s anatomy helps to simplify the surgery, to dramatically reduce the time needed for the surgical procedure and therefore the morbidity and risk of infection for the patient [16,17,18]. In addition, the increased stability of the allogeneic bone block may contribute to faster and better bone healing and graft incorporation/consolidation [14, 15]. In our present study, no gaps were evidenced between the custom-made synthetic scaffolds and the natural bone during the surgery.
In our present study, in addition, the customized allogeneic bone grafts were be adapted on the bone defects using a minimally invasive subperiosteal tunneling technique.
A previous study has assessed the effects of bone block grafting combined with a tunneling technique in animals , but this procedure has never been tested in humans. The procedure described in this paper accurately indexes each prepared allograft block to its corresponding defect site by attaching it directly to the 3D model with screws. This technique enhances adaptation of the preparation by providing a real 3D view of the defect and the possibility of turning around the connection area between the graft and the host site to eliminate any remaining void. This technique also makes it possible to round the outer edge of the block properly so as to not injure the covering flap. Moreover, it is noteworthy that use of a stereolithographic model as a template allows the surgeon to shape the graft without regard to hemostasis or time pressure, while also shortening time of the overall surgery. For this technique we used an allograft instead of an autologous block. The major limitation of autologous bone is the donor site including potential risk of morbidity at the site, impaired tactility and sensitivity and apical pathology .
Irrespective of applied graft materials, the tunnel technique is attractive since it involves a minimally invasive procedure associated with a more conservative surgical entry, while also shortening surgical time and lowering postoperative morbidity (namely flap re-opening, pain and edema). Clinical outcomes observed in this case series are consistent with previous studies that have demonstrated the sub-periosteal tunneling procedure prevents graft exposure with minor postoperative complications [24, 25].
Minimal graft resorption could be observed at implant placement following the 6 month recovery period. Similar results have been reported by Nissan et al.  in 2011, demonstrating a resorption of 0.5 ± 0.5 mm with a similar healing period. In the 25 cases reported on by Nissan et al. , bone blocks were covered with bovine bone particulate mineral or mineralized freeze-dried allograft bone and covered with resorbable collagen membrane. They suggest that minimal resorption is attributable to coverage with the particulate bone and collagen membrane. As such, in the present case series, we obtained similar results without particulate material and membrane. Differences in observations may be related to use of cortico-cancellous and not only cancellous bone block in the present case series, which resulted in a more resistant graft. Indeed, cortical fraction provides adequate rigidity to withstand tension from the overlying soft tissues and/or functional pressure and is less susceptible to resorption [26, 27].
Rigid fixation of the block due to both screw and periosteum pressure is probably one factor contributing to success. Hurzeler et al.  have demonstrated that small movement during the early stages of recovery promoted differentiation of mesenchymal cells into fibroblasts instead of osteoblasts.
Minimally invasive techniques are generally considered to lead to better results in reconstruction processes given the importance of tissue injury influences speed and quality of healing .
The integrity of the periosteum could be one key factor for minimal resorption. This could be expected to improve re-ossification of the reconstructive material based on osteogenic cell penetration and adhesion and neovascularization useful for supplying individual cells with nutrients and oxygen. Indeed, the vascularization process continues over time in the host tissue from the outer area to the volume core. As a consequence, cells located at the core of the graft die faster due to ischemia in the central part, which can result in incomplete colonization [30, 31] that is limited to the external or other layer of the scaffold. Thus, time required for development of the vascular network to the entire graft volume depends on both grafted bone volume and integrity of the periosteum.
The role of the periosteum in osteogenesis and providing mesenchymal cells and osteoblasts is well documented [32,33,34,35]. This has been confirmed by Xuan et al. , who demonstrated a marked difference in new bone formation when placing a bone block through a tunnel with re-ossification at the base of the block and in the more coronal regions of the graft. In contrast, for the conventional flap procedure, new bone is generally limited to the base of the block.
A potential advantage of our present procedure could be the possibility of using a larger bone block with potentially minimal resorption. This can have a high impact on the long-term success of the implant since marginal bone loss around the implant is related to bone thickness . More investigations are needed to confirm this hypothesis because bone volume augmentation is limited by lifting the periosteum to avoid perforation.
Extra cost due to fabrication of the 3D solid model may be a limitation, but it is offset by shortened surgical time, elimination of the covering particulate and the membrane given similar results obtained in this case series. Moreover, the evolution of accurate low-cost printers accessible for a reasonable investment could represent a favorable solution, even in a dental office.
Milling the block using a milling machine has also been suggested [37,38,39,40]. This approach can be useful when a large block with a complex shape is needed for an extensive defect. However, the combination with the tunnel technique can be limited by the size of the vertical releasing incision and laxity of the soft covering tissues. First and foremost, proper positioning of the graft and perfect wound closure must be ensured.
The surface model derived from the 3D CBCT based on the gray scale is open to variability . The accuracy of segmentation is based on the gray-value of each voxel and depends on the threshold value selected by the operator. Thus, this process can differ from one operator to another and may result in loss of surface precision. To overcome those potential limitations, delegating this time-consuming stage to a 3D specialist may be a viable solution in a general clinical practice.
Difficulties in obtaining clear visibility of the site and perfect handling of the graft have been reported, regardless of anatomical considerations. Moreover, close attention must be paid to the perfect fitting of the graft to the recipient bed during the screw positioning stage in order to avoid rotations and misplacement. A learning period is mandatory to achieve adequate and reproducible results.
Our present clinical studies has limits, such as the limited number of patients treated and surgeries performed, as well as the short follow-up time. Moreover, the present technique requires the allogeneic bone blocks to be manually adapted over the jawbone 3D replicas, and this can be considered a limitation of the present study; today, in fact, it is possible to mill custom-made scaffolds using milling machines, with a simplification of the procedures, a reduction of the manual part for the clinician and most of all, a potentially better accuracy [37,38,39,40]. In addition, in the present study, an histologic/ histomorphometric evaluation of the integration of the allogeneic bone blocks is missing; therefore, in the next studies it would be advisable to retrieve bone samples during implant bed preparation, in order to verify the percentage of actually regenerated bone, and that of residual allogeneic bone. Finally, it is important to point out that allografts carry some inherent limitations, such as delayed vascular penetration, slow bone formation, higher rates of bone resorption, and the possibility of immunogenicity and disease transmission . About this last aspect, improved screening, testing, and processing techniques have significantly reduced the risk of infection through bone allografts . However, total sterility is not a practically attainable concept with any human tissue, and in the next future, it is likely that allografts will be replaced by synthetic materials .