How Does Ceramic-Based Scaffold Microarchitecture Impact Maxillofacial Bone Regeneration? A Systematic Review of Large Animal Models  
[PERSON]  
1 Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Boston, MA 02114, USA; [EMAIL_ADDRESS] (A.M.P.B.) [EMAIL_ADDRESS] (Y.M.S. ); [EMAIL_ADDRESS] (P.E.) [PERSON]  
1 Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Boston, MA 02114, USA; [EMAIL_ADDRESS] (A.M.P.B.) [EMAIL_ADDRESS] (Y.M.S. ); [EMAIL_ADDRESS] (P.E.) [PERSON]  
1 Department of Oral and Maxillofacial Surgery, Division of Oral and Maxillofacial Surgery and Implantology, School of Dental, Sao Paulo State University (UNESP), Arcatauba, SP 16015-050, Brazil; [EMAIL_ADDRESS] ([PERSON]  
2 Department of Oral and Maxillofacial Surgery, Translational Implantology, Faculty of Medicine, Medical Center--University of Freiburg, 79106 Freiburg im Breisgau, Germany; [EMAIL_ADDRESS] ([PERSON]  
2 Department of Oral and Maxillofacial Surgery, Translational Implantology, Faculty of Medicine, Medical Center--University of Freiburg, 79106 Freiburg im Breisgau, Germany; feilimchallek@yahoo. diseases, chronic inflammatory conditions, high-energy traumas, congenital anomalies, and oncologic surgeries, among other causes, and require sophisticated approaches to restore both the form and function of the maxillary bones [1; 2]. Bone is a complex tissue, highly vascularized, with an organized and multifunctional structure that must support loads and mechanical stress. It comprises a mineralized matrix and specialized cells in blood cell production and mineral storage. Therefore, reproducing this structure on both macro- and microscales and ensuring that the newly regenerated bone tissue can develop an adequate vascular network is challenging [3; 4; 5; 6]. Critical-sized bone defects (CSBDs) are defined as bone injuries that exceed the intrinsic capacity for spontaneous regeneration and therefore require surgical intervention for healing [7]. In OMS, the reconstruction of critical mandibular defects presents unique challenges due to the mandible's complex anatomy, high mechanical demands, and essential role in aesthetics and function [7; 8]. However, defining what constitutes a CSBD in preclinical research is highly variable, influenced by species-specific, anatomical, and defect-related factors [8]. In large animal models commonly used for translational research--including pigs, sheep, dogs, and non-human primates--mandibular CSBDs are typically defined as defects exceeding 2-3 cm in length or corresponding to volumes greater than 800-3000 mm\({}^{3}\), depending on the species [9]. Segmental defects that involve a loss of peritoneum are particularly critical, as the absence of this vascularized membrane impairs osteogenic potential and complicates spontaneous healing [8; 9]. This variability highlights the need for standardized criteria that integrate defect size, geometry, continuity, and the biological environment. Despite continuous advancements in bone tissue engineering, the lack of a universally accepted definition of CSBDs complicates the comparability of preclinical studies and hinders their translation into clinical practice. Current definitions often rely on simple dimensional thresholds, insufficiently accounting for the complex biological and biomechanical factors that determine regenerative outcomes [7; 8; 9]. Therefore, rigorous preclinical models that accurately simulate the regenerative challenges of the human mandible are essential to evaluate scaffold design, optimize pore architectures, and develop clinically relevant solutions. This systematic review adopts the definition of CSBDs as segmental mandibular defects exceeding 2 cm in large animal models and investigates how ceramic-based scaffold microarchitectures--specifically porosity, pore size, and macroscopic characteristics--influence vascularization, bone formation, and mechanical strength in the treatment of these defects [7; 8; 9].