## 4 Discussion
### Scaffolds
[110] examined the PLGA/HAP scaffold for critical-sized calvaria defects and found numerous biological advantages compared to commercially available xenograft, which were reflected mainly by the lower number of giant cells surrounding implanted material and a higher degree of mineralization in newly formed bone. [PERSON] et al. [114] evaluated the nHAP/PLGA coating scaffold for large segmental defects in the rabbit's ulna. The authors reported almost complete bone regeneration and excellent histological parameters: new bone formation with both endochondral and endosomal types of ossification, high concentrations of BMPs, osteoclastin, and osteopontin within the newly formed bone. [PERSON] et al. [108] evaluated the HAP/PLGA scaffold for the repair of large segmental defects of rabbit radius and exhibited rapid and strong mineralization and osteoconductivity. Previous studies have shown that both the biocompatibility and mandibular bone regeneration performance of composite polymer/bioceramic scaffolds are enhanced compared to polymeric or bioceramic scaffolds [32]. Regarding mandible reconstruction, [PERSON] et al. [36] investigated the HAP/PLGA and HAP/PEI scaffolds for mandibular bone regeneration in a swine model and demonstrated improved biological behavior compared to conventional xenograft in the treatment of swine's mandibular defects in terms of bone density and bone tissue histological characteristics. An interesting finding in this study was the significant activation of osteoclastin, the most abundant noncollagenous protein in bone tissue, produced by osteoblasts in the HAP/PEI cohort. Osteocalcin is an important molecule for the regulation of bone mineral deposition, and its expression can serve as a marker of mineralized matrix formation [36]. Therefore, the ability of composite scaffolds to induce osteoblasts to produce more osteoclastin may be an interesting feature of these biomaterials. Biodegradable metals (BMs) have a variety of properties that are essential for bone regeneration scaffolds, including biodegradability properties, mechanical strength, formability, osteogenic capacity, and antibacterial properties [131]. The most representative BMs are Mg-based, Zn-based, and Fe-based. These materials have been used in manufacturing biomimetic scaffolds, fixation plates, screws, pins, wires, and stents [131]. Mg-based biomaterials are widely used because of their elastic modulus, which is similar to human bones, biosafety, and biodegradability. Fe-based biomaterials have a relatively low degradation rate and insoluble degradation products, which greatly limit their application [132]. Zn-based biomaterials possess a moderate degradation rate and excellent mechanical properties for orthopedic and cardiovascular applications [51]. Critical-sized mandibular defects imply the use of load-bearing tissue scaffolds due to significant masticatory forces. Bioresorbable metallic scaffolds may potentially be used to overcome the mechanical properties of conventional tissue scaffolds. Magnesium and its alloys have outstanding mechanical and biological properties for bone regeneration, including mechanical properties and Young's modulus close to that of cortical bone [133; 134; 135; 136]. Magnesium stimulates bone growth due to the formation of bone-apatite-like HAP crystals [136]. In vitro studies showed excellent mechanical properties of porous magnesium scaffolds with a modified Young's modulus to adjust to one of the cancellous bones (0.01-2.0 Gpa) [134; 135]. The use of Mg-based bone scaffolds may be a promising strategy in future research on mandibular bone regeneration.