Development of a Compromised Maxillofacial Wound Healing Model for Bone Graft Evaluation
Dr. Young’s research interest includes the design of materials for the promotion of bone regeneration in the craniomaxillofacial complex. He has broad experience in the fields of biomaterials, growth factor delivery, in vivo models, and characterization of bone and neovascularization. As an oral & maxillofacial surgeon with experience treating traumatic defects and pathology, Dr. Young understands the unique challenges associated with the reconstruction of complex maxillofacial wounds. By designing a novel preclinical model of compromised wound healing, Drs. Young and Kasper hope to better understand the mechanisms which prevent successful bone grafting, and use these insights to design better therapies in the future.
Despite our understanding of bone regeneration in sites with an optimized underlying physiological environment, it is still poorly understood why bone grafting fails in the setting of the compromised wound (i.e. osteoradionecrosis, multiply-operated sites, etc.). Whether the defect lies in an inadequately vascularized environment, an adversely affected (or missing) progenitor cell population, the complicating presence of bacterial contamination, or a sub-optimal cytokine milieu, the relative contributions of these factors remains to be clearly elucidated. A clinically relevant, reproducible model of compromised wound healing would be invaluable not only to study these potential mechanisms of bone graft failure, but to inform future strategies to improve bone grafting in these situations.
The studies outlined in this proposal seek to build upon our established rabbit mandibular defect model to develop a new pre-clinical model of compromised maxillofacial wound healing for application as a clinically-relevant platform for the elucidation of key differences between compromised and non-compromised maxillofacial wound environments. The novel model of compromised maxillofacial wound healing will be characterized to determine if significant vascular, cellular, or cytokine expression differences are present between the compromised wound healing environment and non-irradiated controls. This model can then be utilized in future studies to characterize the efficacy of various standard bone grafting materials and aid in the fabrication of rationally-designed bone tissue engineering materials.
Stacey L. Piotrowski, Lindsay Wilson, Neeraja Dharmaraj, Amani Hamze, Ashley Clark, Ramesh Tailor, Lori R. Hill, Stephen Lai, F. Kurtis Kasper, and Simon Young. Tissue Engineering Part C: Methods. Mar 2019. ahead of print http://doi.org/10.1089/ten.tec.2018.0361 Full Text