Local Treatment of Meniscal Lesions with Vascular Endothelial Growth Factor

Background: The healing potential in the avascular regions of the meniscus is very limited, and improving the vascularity might be a reasonable way to improve healing. Vascular endothelial growth factor (VEGF) is one of the most potent proangiogenetic factors. We hypothesized that the local application of VEGF165 would (1) improve the healing of a lesion in the avascular region of the meniscus, (2) induce angiogenesis in both the avascular and vascular regions, and (3) increase the amounts of VEGF mRNA and VEGF. Methods: In eighteen sheep, the medial menisci were cut longitudinally in the avascular region and were sutured. Three groups were established depending on the suture material: (1) uncoated Ethibond, (2) Ethibond coated with VEGF165 and its carrier Poly(D,L–Lactide) (PDLLA), and (3) Ethibond coated with PDLLA. The contralateral medial menisci served as a control group. Each of the three suture type groups included six animals. After eight weeks, the sheep were killed, and the menisci were examined macroscopically. Immunohistochemistry of Factor VIII and VEGF and real-time reverse-transcription polymerase chain reaction (RT-PCR) of VEGF mRNA were performed. Additionally, the VEGF release kinetics from the VEGF/PDLLA-coated suture were evaluated in vitro. Results: In this model, VEGF did not improve meniscal healing. It did not increase angiogenesis in the avascular or vascular region, the VEGF concentration, or the amount of VEGF mRNA. VEGF release from the coated suture peaked on Day 3 and was nearly zero on Day 9. Conclusions: The local application of VEGF165 as eluted from suture did not increase meniscal angiogenesis or improve meniscal healing. In addition, there was no effect on the amount of VEGF mRNA and VEGF. The VEGF carrier (PDLLA) may have been inadequate because of the short duration of VEGF supply. Clinical Relevance: This study shows that the application of VEGF at one time point might not be a solution to improve meniscal healing.