Biomechanical characteristics of frozen bone allografts after gene therapy-induced revascularization.

Abstract

Segmental bone loss reconstruction using frozen bone allografts has a great advantage over amputation. Unfortunately, frozen allografts are avascular, and their use often results in infection, non-union, or fracture. We have attempted to overcome these complications by revascularizing the bone using gene therapy. Segmental tibial bone transplants were performed in 16 Yucatan minipigs. An arteriovenous (AV) bundle was placed intramedullary inside the allografts, which were transfected with growth factors vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) in 8 out of the 16 pigs. Survival time was set at 20 weeks. Bone remodeling and biomechanical properties were tested using histology, compression testing, bone mineralization, and gait analysis. In the growth factor group, five out of eight pigs developed cutaneous vascular tumors, causing excessive bleeding, which led to the exclusion of one pig. Bone remodeling was significantly more present in the VEGF group compared to the control group. This correlated with the amount of pressure the pig allowed on the operated leg for 10 weeks, which was also significantly more (p = 0.029) than the control. Both bone mineralization (p = 0.156) of the area inside the cortex and the amount of stress the allograft could endure before breaking (p = 0.078) seemed to be no different for the VEGF group compared to its healthy contralateral side, which was the control group. We have shown that growth factor-induced frozen allograft bone revascularization using an intramedullary AV bundle results in significantly more bone remodeling and better biomechanical bone properties. However, we encountered benign vascular cutaneous tumors in five out of eight pigs, making the clinical application of this technique impossible at this time.