# Personalized Bone Reconstruction and Regeneration in the Treatment of Craniosomiasis
## 2 Biomaterials and Tissue Engineering Approaches
### Tissue Engineering Strategies
For example, PLA presents relatively high mechanical properties (flexural strength up to 140 MPa, Young's modulus 5-10 GPa, total tensile elongation about 3%, Charpy impact fracture -2.5 kJ/m\({}^{2}\)), with excellent optical properties, good processing ability (with low shrinkage not causing product deformation) and biodegradation time over the period of several months up to two years [103]. On the other hand, PCL is a biodegradable polymer with very high flexibility, a tensile strength between 4 and 785 MPa and a Young's modulus in the range 0.21-0.44 GPa, presenting a degradation time of 2-to-3 years [104]. In particular, to contain/avoid the recurrence of suture fusion following surgical resection (re-synostosis) in CS patients, innovative approaches could derive from the design of biomaterials able to tame tissue mineralization. The combination of biomaterials with stem cells and osteoprogenitor cells allows implementing the osteogenicity in the tissue engineering approach. Nonetheless, cell-based treatments involve additional drawbacks, mainly ascribable to immune-related issues, along with increased production costs. On the other hand, the use of autologous cells to overcome the risk of immune rejection implies additional morbidity at the tissue harvesting site (bone marrow, adipose tissue, etc. ), and hampers their exploitation in younger patients, for whom a real clinical translation of advanced cell-based therapies for CS treatment cannot be foreseen. Different studies tested the feasibility of tissue engineering approaches for the treatment of membranous bone critical-size defects, relying on either cell culture systems or animal models (see Table 4). In particular, [PERSON] and coworkers [105] produced apatite coated poly-lactic-co-glycolic acid (PLGA) (PLA:PGA 85:15) scaffolds through solvent casting and a particulate leaching process, and seeded them with adipose-derived stromal cells (ASCs) or bone marrow stromal cells (BM-MSCs). They evidenced a remarkable intramembranous bone formation by 2 weeks and areas of complete bony bridging by 12 weeks, after in vivo implantation in adult male FVB mice (FVB is an albino, inbred laboratory mouse strain that is named after its susceptibility to Friend Leukemia Virus B), suggesting that ASC cells are able to repair critical-size skeletal defects without genetic manipulation or the addition of exogenous growth factors [105]. This supports the idea that the microenvironment at the bone defect site could induce the osteogenic commitment of extraskeletal MSCs, such as ASCs, on appropriate scaffolds promoting efficient bone healing in vivo [106; 107]. A recent study lead by [PERSON] et al., demonstrated the efficacy to restore coronal suture patency in a Twist1\({}^{+/-}\) mice Model using Gli1\({}^{+}\) MSCs combined with methacrylated gelatin (GelMA) modified with Matrigel and collagen I (COL-I) [108]. GelMA (M-GM) scaffold is highly biocompatible and biodegradable, and it easily adapts to defects [109]. The Authors showed that loss of Gli1\({}^{+}\) MSCs induces premature coronal suture fusion in Twist1\({}^{+/-}\) mice, confirming that this subpopulation of MSC are largely required for craniofacial bone turnover, homeostasis and repair [110]. They also showed that the implantation of MSC-graft leads to suture regeneration by restoring Gli1\({}^{+}\) cells subpopulation within cranial suture both through exogenously implanted Gli1+ MSCs and endogenous MSCs derived from the _dura mater_[108]. Our group has indeed recently demonstrated that GLII1 represents a specific marker for MSC in the human calvarial niche [21]. Additional biomaterials have been tested as suitable scaffolds for CS skull reconstruction, by studying their interaction with cells in vitro.