van den Berg, Catherine

AbstractSegmental bone defects are often performed with cryopreserved allografts. They provide immediate stability, but risk nonunion, infection and late stress fracture. Improving the rate and extent of bone revitalization may improve results. Angiogenesis from surgically placed arteriovenous (AV) bundles improves bone blood flow and vitality in cryopreserved rat femora, augmented by vasculogenic growth factors. This study tests the same principal in Yucatan mini‐pigs with a tibial diaphyseal defect, combining surgical angiogenesis with angiogenic gene therapy within cryopreserved orthotopically‐placed allografts. Tibial diaphyseal defects were reconstructed with cryopreserved allografts and rigid internal fixation in 16 mini pigs. Half of the cranial tibial AV bundles placed within the allograft medullary canal were transfected with an adeno‐associated virus containing vascular endothelial growth factor (VEGF) and platelet‐derived growth factor (PDGF) genes (AAV9.VEGF.PDGF). Bone remodeling, angiogenesis, and allograft healing were assessed. During the postoperative survival period 5 of 8 transfected animals developed cutaneous benign vascular lesions at sites remote from the operated hindlimb, causing excessive bleeding. Within the allograft, both medullary (p = 0.013) and cortical (p = 0.009) vascular volumes were higher and vessels more mature than nontransfected allografts. Bone turnover (p = 0.013), bone mineralization (p = 0.018), bone healing (p = 0.008) and graft incorporation (p = 0.006) were all significantly higher in the gene therapy group. In a large animal tibial defect model, gene therapy of implanted AV bundles improved revascularization, remodeling and healing of cryopreserved allografts used for limb reconstruction. However, benign vascular lesions causing excessive bleeding developed in 5 out of 8 pigs transfected with AAV containing genes for VEGF and PDGF. This unforeseen complication makes vasculogenic gene therapy unacceptable for clinical use.

Background: Adult traumatic brachial plexus injuries (BPIs) can result in severe impairment following penetrating wounds, falls, and motor vehicle accidents or other high-energy trauma. Objective: Quantify functional outcomes of adult patients with a BPI using a myoelectric orthosis to restore elbow flexion. Study design: Retrospective review. Methods: A clinic specializing in the BPI treatment at a large academic medical center tested nineteen adult patients with BPI. These patients had failed to achieve antigravity elbow flexion following their injury and observation or surgical reconstruction. They were provided a myoelectric elbow orthosis (MEO) if they had detectable electromyography signals. Results: There was significant improvement in strength and significant reductions in function and pain when using an MEO. Following initiation of the MEO, 12 of the 19 patients had clinical improvements in muscle strength, 15 patients showed improvement in their DASH, and 13 patients reported improvements in their Visual Analog Scale. Conclusion: The use of an MEO improves elbow flexion strength, increases function, and reduces pain in the majority of patients with BPI and inadequate elbow flexion following observation or surgical reconstruction.