## 4 Discussion
### Scaffolds  
Based on the results of the present review, the use of scaffolds in mandibular bone regeneration, alone or in combination with bioactive molecules and/or cell therapies, resulted in improved osteogenesis of critical-sized mandibular defects in various animal models. The most promising results in mandibular bone regeneration were observed with composite scaffolds. Scaffolds for BTE can be classified into four classes: polymeric, ceramic, composite, and metallic scaffolds. Natural polymeric scaffolds have excellent biocompatibility and controlled biodegradation [20]. Natural biopolymers are used for maxillofacial bone regeneration because they mimic the structure, chemical composition, and biochemical properties of the natural ECM bone organic matrix and have osteoinductive and osteoconductive properties. This was demonstrated by their ability to induce bone regeneration in mandibular bone defects. The major drawbacks of natural polymers are their poor mechanical properties, which do not approach those of natural bone tissue, and the high degradation rate of natural polymers, since they are naturally metabolizable [110]. The most commonly used natural polymeric scaffolds implemented for mandibular bone regeneration were hyaluronic-acid-based and collagen. Due to their excellent biological properties, natural polymers are extensively studied in composite scaffolds for bone repair. Several investigations have indicated that incorporating inorganic components, such as hydroxyapatite (HAP), or tricalcium phosphate (TCP), into hybrid hyaluronic-acid-based (HA) scaffolds results in enhanced osteoinductivity, osteoconductivity, and improved mechanical properties [111; 112]. Natural polymers are versatile, encapsulating bioactive osteogenic factors (growth factors, drugs, hormones, peptides, nucleic acids, and cells) via a cross-linking reaction [113; 114; 112]. Recent studies reported excellent the bone regeneration of rabbit mandibular bone defects using nano-hydroxyapatite/collagen (nHAC) scaffolds with concentrated growth factors (CGF). The results of these studies showed degradation of the scaffold within 24 weeks, a high rate of new bone formation, and higher compressive strength and elastic modulus on biomechanical tests of the nHAC/CGF group compared to those of the nHAC group [99; 100]. Synthetic polymers are aliphatic polyesters, and their copolymers are commonly utilized polymers in bone tissue engineering due to their mechanical properties. They are biocompatible, biodegradable, easily fabricated into different shapes, and provide mechanical support and a controlled degradation time. Their use in bone engineering is limited due to their decrease in mechanical strength due to rapid degradation in vivo and immune reaction to acidic degradation products. The chemical modification of syntheticpolymers allows for the incorporation of bioactive molecules to produce biocompatible and functional materials to enhance osteogenesis. One of the major advantages of synthetic polymers is that they can be mass-produced and fabricated for individual bone sites. The traditional preparation methods of synthetic-polymer-based bone scaffolds include particle leaching, phase separation, gas forming, and fiber bonding. The 3D printing technology produces porous scaffolds by managing the arrangement of the scaffold, the thickness of each layer, and the porosity [115]. The 3D-printed scaffolds achieved better cell adhesion, proliferation, and differentiation while possessing suitable mechanical properties and a sufficiently long degradation time [116]. Recent studies have developed grafts for the mandible, skull, femoral head, tibia, fibula, and others [117]. Poly(lactic-co-glycolic acid) (PLGA), a linear copolymer of lactic acid and glycolic acid monomers, was the most widely used biodegradable polymer.