Advisor: Robert E. Guldberg, Ph.D. (Georgia Institute of Technology)
Johnna S. Temenoff, Ph.D. (Georgia Institute of Technology)
Krishnendu Roy, Ph.D. (Georgia Institute of Technology)
Greg Gibson, Ph.D. (Georgia Institute of Technology)
Steven L. Stice, Ph.D. (University of Georgia)
Patient-specific Approaches to Bone Regeneration
The first recorded bone grafting procedure was performed by Dr. Job van Meekeren in 1668, who transplanted a fragment of dog skull into the skull of a wounded soldier. Today, bone is the second-most transplanted tissue after blood with more than 1.6 million bone grafting procedures performed annually in the US at a cost of over $5 billion. Treatment of large bone defects in particular remains one of the most challenging problems faced by orthopedic surgeons. Current therapies include bone grafts and/or delivery of osteoinductive proteins such as bone morphogenetic protein 2 (BMP-2). Despite advances in surgical technique and medical care, many of these treatment options still exhibit high variability in patient outcomes, suggesting that patient-specific factors, such as age, treatment timing, and immune status, may play a much more pivotal role in long-term treatment success than previously thought. Thus, the need to account for these patient-specific factors with more sophisticated treatment strategies has become increasingly apparent.
The main objective of this project is to use preclinical animal models to investigate how patient-specific factors influence biomaterial-mediated bone regeneration. Preliminary work suggests that better understanding of these factors will motivate a targeted immunomodulatory therapy for improving bone regeneration. The impact of age on large bone defect healing will be elucidated using an established bone injury model along with delivery of rhBMP-2 in a collagen sponge, which is the current clinical standard. These results may provide valuable insight on a controversial subject: the use of rhBMP-2 in pediatric patients. Additionally, this work will identify some of the key mechanisms that lead to nonunion, a significant clinical problem that affects up to 10% of patients with long bone injuries. Along the way, a chronic nonunion model will be developed that can potentially serve as a more rigorous and clinically relevant platform for testing new technologies and therapeutics. Finally, the issue of trauma-induced immune dysregulation will be explored and the novel approach of immunomodulation to enhance bone repair will be assessed. Collectively, these studies will advance our understanding of the factors that affect bone regeneration and represent a critical step towards improved, more personalized care and management of patients recovering from orthopedic trauma.