Sodium hyaluronate as a drug-release system for VEGF 165 improves graft revascularization in anterior cruciate ligament reconstruction in a rabbit model

Abstract

Graft remodeling following anterior cruciate ligament (ACL) reconstruction requires a long period of recovery in which vascular endothelial growth factor (VEGF) plays an important role. The short half-life of exogenous VEGF, however, restricts its use. The aim of this study was to investigate sodium hyaluronate (SH) as a delivery system for VEGF in graft revas-cularization. Non-cumulative release into phosphate-buffered saline (PBS) was firstly measured spectrophotometrically for 1-4 days. Allogeneic bone-patellar tendon-bone (B-PT-B) was soaked in the VEGF/SH formulation and implanted in a rabbit model to regenerate the ACL and observe the vascularization and biomechanical properties. The results revealed that a steady state was achieved after ~40 h in non-cumulative measurements. The release plotted as a function of the square root of time was consistent with a largely diffusion-controlled release system. At 2, 4 and 8 weeks, the microvessel density of grafts was higher in the VEGF/SH-treated group compared to the control groups. Although there was a temporary decline at 2 weeks, the stiffness and maximum tensile load of the experimental group was significantly greater than that of the control group at 4 and 8 weeks (P<0.01). Our findings suggest that SH can be used as a good carrier of VEGF, which can improve the early revascularization and biomechanical properties of B-PT-B allografts after ACL reconstruction.