## 4 Discussion
However, their limited anatomical and biomechanical similarity to humans restricts direct clinical extrapolation. Furthermore, rodents exhibit a markedly accelerated bone healing and remodeling process compared to large animals and humans, which can overestimate the regenerative potential of tested scaffolds. In contrast, larger animals such as canines provide closer anatomical analogs for mandibular reconstruction, allowing for more realistic functional and mechanical evaluations. These models also better replicate the slower bone healing kinetics and immune response seen in humans, offering more clinically relevant insights. Notably, as demonstrated by [PERSON] et al. (2022) [32], minipigs emerge as an ideal translational platform due to their bone density, vascularization, and load-bearing characteristics, which closely resemble human physiology. Recognizing these species-specific biological differences is crucial for interpreting preclinical outcomes and optimizing scaffold design for successful clinical translation. In terms of biomaterials and scaffold design, the incorporation of \(\beta\)-TCP, HA, and BCP with osteoinductive agents, such as rhBMP-2, MSCs, or BMSCs, has significantly enhanced osteogenesis and mechanical properties across various studies [29; 35; 36; 46]. Additionally, customized 3D-printed scaffolds [26; 27] enabled better anatomical adaptation and more efficient bone regeneration, thereby reinforcing the potential for personalized reconstruction strategies. These advances are especially relevant for clinical applications in orthodontic and orthognathic contexts, where the integration of tissue engineering techniques can enhance treatment outcomes by supporting skeletal corrections and improving bone healing in complex craniofacial procedures [46]. Potential clinical applications are further strengthened by findings indicating that bone substitutes can achieve biomechanical performance comparable to native bone, as observed by [PERSON] et al. (2007) [35] and [PERSON] et al. (2021) [27]. This suggests that such materials could represent viable alternatives to autologous grafts, thereby minimizing donor site morbidity. Furthermore, innovative strategies, such as pre-vascularization or pre-implantation in muscle tissue, demonstrated by [PERSON] et al. (2009) [33], highlight promising approaches for addressing complex clinical scenarios that require functional bone regeneration. Nevertheless, despite these encouraging results, several challenges remain. Variability in scaffold compositions, animal models, defect types, and evaluation methodologies across studies underscores the need for greater standardization. Moreover, longer-term studies assessing scaffold degradation and bone remodeling are crucial for fully validating the translational potential of these biomaterials. Research focused on identifying the optimal biomaterial and its ideal characteristics has revealed a significant gap in the standardization of geometric parameters. There needs to be a consensus on the ideal dimensions and shapes of the biomaterials used, which complicates the comparison between studies and the reproducibility of results. Studies must rigorously address these characteristics to ensure consistency and achieve an ideal standard. Although conventional techniques often do not precisely control these characteristics, advancements in manufacturing methods offer a unique opportunity to standardize scaffold designs, allowing for the more precise control of essential properties and bringing us closer to more effective and reproducible solutions.