TGFβ-1 and Healing of Bone Defects in Large Animal and Rabbit Models: A Systematic Review

Long bone and craniofacial bone fractures amount to an overwhelming expenditure for patients and health care systems each year. Overall, 5-10% of all bone fractures result in some form of delayed or nonunion fractures. Nonunions occur from insufficient mechanical stabilization or a compromised wound environment lacking in vasculature and progenitor cells. The current standard for treating these critical-sized fractures and defects is the use of autologous bone grafts. However, advancements in tissue engineering have cultivated a shift in scientific efforts toward harnessing the body's own regenerative resources. As such, research on fracture healing has shifted as well. Transforming growth factor-beta 1 (TGFβ-1) has been studied in fracture healing for over 25 years, though many of these studies have been in vitro or in small animal models. The few studies in large animals have disagreement due to the heterogeneity within the experimental design. Because TGFβ-1 plays such a crucial role in the bone healing process, this systematic review investigates the application of TGFβ-1 in various carrier vehicles for repairing bone injuries in large animal and rabbit models. A systematic search was conducted in PubMed, Embase, and Web of Science (from database construction-October 2024). A total of 244 articles were screened, and 24 studies were included for review. Most large animal long bone studies used coated titanium implants, while most rabbit long bone studies used some form of degradable polymer constructs. TGFβ-1 doses in large animal long bone studies range from 0.005 to 750 µg, doses in large animal calvaria and mandible studies range from 1 to 5000 µg, and doses in rabbit long bone studies range from 0.05 to 120 µg. Nineteen out of 24 articles reviewed indicate successful use of TGFβ-1 for bone regeneration compared with experimental controls. It is clear that dose and controlled release of growth factor play a crucial role in defect closure, but outcome measures and success criteria were inconsistent across studies. More studies with consistent experimental designs are critical for understanding the therapeutic potential of TGFβ-1 in fracture repair, but overall, this review indicates that TGFβ-1 can be used alone or in conjunction with other growth factors to accelerate successful bone repair.