# Personalized Bone Reconstruction and Regeneration in the Treatment of Craniosomiasis
## 4 Clinical Perspectives and Actual Clinical Translation  
Even if important advancements have been achieved in adult craniofacial bone tissue engineering [196], an optimization for use in the pediatric population has not been reached yet [197; 198]. A personalized approach is needed for treating pediatric patients to take into account multiple features: the reduced bone thickness [199], the decrease of _dura mater_'s osteoinductive potential after 12 months [200], and the dynamic growth and development of the craniofacial skeleton requiring multiple surgical treatments [201]. Thus, an ideal pediatric bone replacement would satisfy a lot of requirements to re-establish the functionalities of the skeleton without avoiding craniofacial development [198; 199]. This is particularly relevant in the treatment of congenital bone developmental defects. In craniosynostosis care, cranial surgery for bone reconstruction should concurrently cope with the need to hamper premature suture fusion, to allow the correct pace for braincase enlargement along with the harmonic craniofacial development. In the present review, the advantages of the surgical approaches were compared, in terms of both topology of the suture involved and of the possible clinical strategies to be implemented. Although several tissue engineering approaches have been designed and tested in preclinical studies, it is evident that, regardless of the surgical approach, an optimized device/scaffold to promote the calvarial bone regeneration, while simultaneously preventing the excessive bone formation at the site of suturedomy, thereby avoiding re-synostosis, has not reached an universal consensus to be stably translated in the clinical practice. The use of additive manufacturing techniques for a customized replication of the architecture of the skull and bony defects, based on tomographic data, would facilitate the achievement of this ambitious purpose, promoting surgical placement and retention of the engineered scaffold. Therefore, based on such considerations, the application of bone tissue engineering strategies in this specific pediatric context is limited and at an infancy state [202]. Nevertheless, the everlasting efforts of the scientific community have achieved some specific advancements in the field of novel biomaterials and drug delivery systems. A unique gold standard polymer or compound cannot be universally defined, also due to the wide and heterogeneous spectrum of CS entities (Tables 1 and 2), offering a correspondingly wide range of outcomes and suggesting the need for personalized strategies. On the other hand, a consensus seems to emerge from the extant literature reviewed in this paper: injectable gel formulations are probably the more suitable to be implemented as a tissue engineering approach in CS surgery (Table 5). To achieve a feasible personalized bone regenerative treatment for CS, novel data are expected to arise from the development of 3D human culture systems, able to mimic the patient-specific in vivo environment, as platform for improved ex vivo preclinical testing. Finally, given the crucial aspect of timing in CS surgery, the current pandemic situation that has led to delay of elective surgeries, posed CS care in a critical position, at least in selected healthcare systems, worldwide. Indeed, postponing the schedule of CS surgical treatment may cause increased risk of disease progression, including enhanced intracranial pressure and completion of suture fusion, hence raising the demand for more invasive and higher risk procedures, such as open vault surgery [203]. This aspect could reasonably emerge as an additional Covid-19 side effect affecting pediatric patients, and will further prompt the improved implementation of bone reconstructive strategies and personalized tissue engineering approaches in craniofacial surgery. **Author Contributions:** Conceptualization, I.C., G.N., A.A. and W.L. ; methodology, F.T., I.C., P.F., G.T. ; formal analysis, W.L. and A.A.; data curation, F.T.