The purpose of this study was to develop a cell-based VEGF gene therapy in order to accelerate fracture healing and investigate the effect of VEGF on bone repair in vivo.

Twenty-one rabbits were studied. A ten millimeter segmental bone defect was created after twelve millimeter periosteal excision in the middle one third of each tibia and each tibia was plated. Primary cultured rabbit fibroblasts were transfected by use of SuperFect (Qiagen Inc) with pcDNA-VEGF. 5.0 X 106 cells in 1ml PBS were delivered via impregnated gelfoam into the fracture site. Experimental groups were:

Transfected fibroblasts with VEGF (n=7),

Radiology: Fracture healing was defined as those with bone bridging of the fracture defect. After ten weeks, fourteen tibial fractures were healed in total including six in group one, four in group two and four in group three. The VEGF group had an earlier initial sufficient volume of bridging new bone formation. Histological evaluation demonstrated ossification across the entire defect in response to the VEGF gene therapy, whereas the defects were predominantly fibrotic and sparsely ossified in groups two and three. Numerous positively stained (CD31) vessels were shown in the VEGF group. MicroCT evaluation showed complete bridging for the VEGF group, but incomplete healing for groups two and three. Micro-CT evaluation of the new bone structural parameters showed that the amount of new bone (volume of bone (VolB) x bone mineral density (BMD)), bone volume fractions (BVF), bone volume/tissues (BV/TV), trabecular thickness (Tb.Th), number (Tb.N) and connectivity density (Euler number) were higher; while structure model index (SMI), bone surface/bone volume (BS/BV), and trabecular separations (Tb.Sp) were lower in the VEGF group than the other groups. P-Values < 0.05 indicated statistical significance (ANOVA, SPSS) in all parameters except for SMI (0.089) and VolBx-BMD (0.197).

These results indicate that cell-based VEGF gene delivery has significant osteogenic and angiogenic effects and demonstrates the ability of cell based VEGF gene therapy to enhance healing of a critical sized defect in a long bone in rabbits.

Introduction and Aims: Midcarpal instability is a common cause of wrist pain that remains poorly understood. A simple surgical treatment has been developed involving plication of the dorsal wrist capsule and ligaments. We hypothesised that: wrist stiffness varies in the population; laxity permits excessive displacement; and plication stiffens the joint decreasing motion.

Method: Twelve human cadaveric forearms were potted using bone cement and were secured to the stationary baseplate of a slider. The hand was fixed through the metacarpal bones to the mobile section of the slider, and a compressive load was applied. With the wrist positioned in neutral orientation, a force was applied by an Instron mechanical testing machine (Model 8874, Instron, Canton, MA), simulating a midcarpal shift test. Stiffness (force/displacement) was measured at baseline, with the capsule sectioned, and then following a surgical procedure consisting of plicating the ligaments and capsule with three mattress sutures at the midcarpal joint.

Results: Baseline testing revealed large variability in midcarpal joint stiffness: mean baseline stiffness was 16.5 + 5.9 N/mm, ranging from 9.3 to 28.1 N/mm. Following plication/repair, mean stiffness increased significantly by 20% to 19.8 + 8.5 N/mm (p < 0.02). All surgical repairs withstood the testing without failure. These data confirm a wide range of laxity at the midcarpal joint and provide a mechanical basis for the success observed with capsular plication of the joint.

This increased stiffness decreases motion under comparable loading conditions. In individuals who have excessive motion causing wrist symptoms, increasing the stiffness by capsular plication of the supporting ligaments decreases the motion to relieve symptoms. This technique has found success in clinical practice to relieve symptoms in patients with midcarpal instability.

Conclusion: Midcarpal joint stiffness spanned a threefold range supporting our hypothesis that there is a large variation of ligament laxity in the population. Suturing the dorsal wrist capsule and underlying ligaments significantly increased the stiffness of the wrist when a volar force was applied across the midcarpal joint.