# Personalized Bone Reconstruction and Regeneration in the Treatment of Craniosomiasis
## 2 Biomaterials and Tissue Engineering Approaches
### Tissue Engineering Strategies  
Despite significant innovation in the management of CS, morbidity and mortality still exist. Residual cranial defects represent one of the potential complications. In fact, all the surgical correction techniques rely on spontaneous ossification of the surgical bone defects. In spite of a proper preservation of _dura mater_ and periosteum, critical size cranial defects may result in a large proportion of cases, from incomplete or defective spontaneous healing of the bone [79] or other surgical complications (i.e., infection or resorption of the bone flap) especially when multiple repeated surgeries are required, as in the case of re-synostosis [80]. The resulting cranial defects may represent a serious issue in paediatric neurosurgery [81; 82]. The common procedures adopted in these cases involve the use of either autologous bone grafts, or allogeneic grafts, or alloplastic materials to fill the bone gap. The use of autologous bone and avoidance of heterologous material is pursued, since an ideal bone substitute is lacking and complications of heterologous materials are higher in children [46]. Cranial bone splitting may be considered for small to medium-size defects [83]. In large size (>5 cm\({}^{2}\)) defects, the options are very limited. Biobanked bone-derived products, such as demineralized bone matrix (DBM) and bone dust (BD), represent potential alternatives to autologous bone. A recent study assessed the outcomes of DBM plate implantation, with or without bone dust, for the treatment of large calvarial defects resulting from cranial vault surgery in CS patients above one-year-old [74]. Their results indicated a statistically significant improvement of bone healing of calvarial defects receiving DBM plus BD compared with patient-matched control defects, without any complication, particularly in older patients [84]. Certainly, in the last years, the introduction of custom-made implants has warranted better esthetical outcome and reduced complications with respect to synthetic materials that were molded intraoperatively, namely, bone cements and polymethyl methacrylate (PMMA). However, the long-term outcome of the heterologous materials is poorly documented through the literature, though most of them have shown good results in the short-term period. This is the main reason that has prompted the research of biomimetic materials, to improve osteointegration and reduce complications. The most exploited materials for traditional adult skull reconstruction (i.e., PMMA, PMMA hybrid cements, titanium, polyetheretherketone (PEEEK), and mesoporous hydroxyapatite (HAp)), present significant limitations that make them poorly suitable for treating the growing skull of paediatric patients [85; 86; 87; 88; 89]. Porous HAp is widely used as material for cranial defects in paediatric patients, due to its similarity to the inorganic component of the bone extracellular matrix [90; 91], yielding limited foreign body reactions and excellent cosmetic results. Nonetheless, it presents several drawbacks, including the brittle nature, the low tensile strength, and the high infection rates [92]. Cranial implants based on macroporous hydroxyapatite have been increasingly used with satisfactory results in children [93; 94]. However, these implants are not indicated under two years of age, so that a real solution for the repair of large