The Effects of Novel Peptide PR1P on Fracture Repair: An Insight into VEGF Modulation on the Bone Healing Process

Abstract

Fracture healing is a highly regulated process dependent on angiogenesis and osteogenesis, both of which are modulated by vascular endothelial growth factor (VEGF). While VEGF is crucial for vascular invasion and bone regeneration, its rapid degradation in vivo limits its therapeutic potential. This study investigates the efficacy of PR1P, a novel peptide that binds to and stabilizes endogenous VEGF, in enhancing fracture repair. Using a murine femoral fracture model, PR1P was administered intraperitoneally every other day for either 5 or 14 days post-injury. Healing was assessed at days 5, 14, and 28 using micro-CT, RT-qPCR, histology, and immunohistochemistry. Results demonstrated that short-term PR1P treatment enhanced early angiogenesis and chondrogenesis, while prolonged administration promoted angiogenic maturation, osteogenic gene expression, and normalization of bone remodeling by day 28. Notably, extended PR1P exposure mitigated the decline in bone mineralization seen with shorter dosing and supported more coordinated transition from repair to remodeling phases. These findings position PR1P as a promising VEGF-stabilizing therapeutic that can enhance bone regeneration by extending endogenous VEGF signaling during critical phases of fracture healing.