Modulation of digital flexor tendon healing by vascular endothelial growth factor gene transfection in a chicken model

Abstract

A major challenge in tendon injury is the weak intrinsic healing capacity of tendon that may cause rupture of the repair after surgery. Growth factors are believed to be critical during tendon healing. This study aimed to investigate the effects of vascular endothelial growth factor (VEGF) genes delivered by adeno-associated virus (AAV) vectors on tendon healing and molecular events involved in a chicken model. A total of 128 deep flexor tendons in the long toes of chickens were completely transected and injected with 2 × 10⁹ particles of AAV2-VEGF or saline before surgically repaired. At postoperative 4, 6 and 8 weeks, the gliding excursions of tendon were recorded and adhesions around the repair site scored. At 2, 4, 6 and 8 weeks, the ultimate strengths of the healing tendons were tested. Terminal deoxynucleotide transferase dUTP nick end labeling assay were performed to detect cellular apoptosis and immunofluorescence staining to detect type III collagen and matrix metalloprotease-2 (MMP2) expression in tendon tissues. The gliding excursion and adhesion score were similar between AAV2-VEGF-treated tendons and the control tendons. Delivery of AAV2-VEGF significantly increased ultimate strength of the healing tendons at postoperative 4, 6 and 8 weeks (P<0.05). Apoptotic reaction was inhibited from postoperative 2 to 8 weeks in tendon core area or surface area. Type III collagen expression was enhanced at 2, 4, 6 and 8 weeks and MMP2 expression enhanced at 2 and 4 weeks after AAV2-VEGF transfection. The current study confirms the therapeutic efficacy of AAV2-VEGF in improving healing strength of tendon without aggravating adhesion formation after tendon injury, shedding light on the application of molecular therapy in modulating tendon healing.