909. Comparison of Early Stage Healing Responses of Injured Flexor Tendons with Tissue Reactions after Delivery of Adenoviral and Adeno-Associated Viral Vectors to Digital Flexor Tendons

Abstract

Top of pageAbstract PURPOSE Delivery of growth factors that may substantially increase the healing rate of injured digital flexor tendons is a new arena of application of gene therapy. So far adenoviral, adeno-associated viral (AAV), and liposome-mediated plasmid vectors have been used to deliver growth factor genes to tendons or tenocytes, but tissue reactions of these vectors in tendons, in particular those in contrast of healing responses of the injured tendons, were unknown. The purpose of this study was to compare tissue reactions of these vectors in tendons and those of healing responses of injured flexor tendons. METHODS Flexor digitorum profundus tendons within sheath area of paws of 4 New Zealand white rabbits were used as a model. Adenoviral vector (Ad5-lacZ), 1 |[times]| 1010 viral particles, was injected into each of 9 tendons, and AAV2-luciferase, 1 |[times]| 1010 viral particles, was injected into each of 9 tendons. pCMV-b mixed with 3.5 |[mu]|L of lipofectamine was injected into each tendon. In other 9 tendons, the tendons were cut through volar 2/3 transversely and repaired. At 3, 7, and 14 days, the tendons were harvested and stained with hematoxylin and eosin. Normal tendons were harvested, serving as control. RESULTS Tissue reactions of the liposome- plasmid vectors in tendons were the most prominent among 3 vectors tested. The adenoviral and AAV2 vectors showed similar tissue reactions at the same viral titers tested, but AAV2 had less obvious tissue reactions in the endotenon area than adenoviral vectors. Early stage inflammatory changes were remarkable in the injured tendons. Compared with these tissue reactions, the reactions elicited by the vectors were less severe. CONCLUSIONS The tested 3 gene delivery systems had less severe tissue reactions in flexor tendons compared with inflammatory changes in injured flexor tendons in early stage. Among 3 vector systems tested, adenoviral and AAV vectors elicited less tissue reactions than liposome-plasmid vectors. AAV2 causes less severe reactions in the endotenon area than adenoviral vectors. From the perspective of tissue reactions, adenoviral and AAV2 vectors, in particular AAV2, are advantageous gene delivery systems for future investigation of delivery of genes to promote flexor tendon in vivo.