Development and Characterization of a Rabbit Model of Compromised Maxillofacial Wound Healing

Background: Tissue engineering technologies aiming to enhance maxillofacial wound healing are often tested in vivo in preclinical models that do not necessarily reflect the complexity of the clinical need. The aim of this study was to develop a rabbit model of compromised craniofacial wound healing that more accurately mimics clinical scenarios. Materials and Methods: An experimental group of rabbits received fractionated radiation of the mandible totaling 36 Gy. Four weeks after irradiation, both the experimental group and control group (n = 10/group) underwent a surgical procedure creating a critical size defect in the mandibular bone. Four weeks after surgery, tissue healing was assessed using microcomputed tomography (μCT), maximum intensity projection (MIP) scoring, and histopathology. Results: μCT analysis and MIP scoring showed decreased mineralized tissue in the defect area of irradiated animals compared to the control group. Histopathology showed necrosis in the experimental group. Conclusions: Irradiated animals showed significantly compromised wound healing compared to controls. This preclinical model presents a clinically relevant environment for the investigation of novel wound healing technologies in a compromised critical size bone defect. IMPACT STATEMENT: Maxillofacial defects often present the clinical challenge of a compromised wound bed. Preclinical evaluation of tissue engineering techniques developed to facilitate healing and reconstruction typically involves animal models with ideal wound beds. The healthy wound bed scenario does not fully mimic the complex clinical environment in patients, which can lead to technology failure when translating from preclinical in vivo research to clinical use. The reported preclinical animal model of compromised wound healing enables investigation of tissue engineering technologies in a more clinically relevant scenario, potentially fostering translation of promising results in preclinical research to patients.