Feasibility of percutaneous gene transfer to an atrophic nonunion in a rabbit.
Treatment of atrophic nonunions is a challenge to orthopaedic surgeons. Growth factors potentially are valuable factors for improvement of tissue healing. The use of growth factors, however, is limited by their short half-lives. Gene therapy has the potential to improve the treatment. This study aimed to establish and validate an atrophic nonunion model in a rabbit for the use of a percutaneous in vivo gene therapy protocol. An atrophic tibial nonunion was established in 24 New Zealand White rabbits. Radiologic and histologic followup was for 64 weeks. The rabbit tibias showed no radiologic or histologic signs of healing. In addition, an adenoviral vector carrying a marker gene was injected percutaneously into the nonunion site in 12 rabbits. Expression of the marker gene was assessed for as many as 4 weeks. The percutaneous gene delivery resulted in transgene expression in the nonunion site for as many as 4 weeks. The described model reliably leads to an atrophic tibial nonunion in rabbits. Adenoviral percutaneous gene delivery into the nonunion site is feasible and leads to transgene expression locally for at least 1 month. This study provides investigators with a reliable and reproducible model of an atrophic nonunion.
Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA. lattermannc@msx.upmc.edu
Christian
C
Lattermann
Axel W
AW
Baltzer
Boris A
BA
Zelle
Janey D
JD
Whalen
Christopher
C
Niyibizi
Paul D
PD
Robbins
Christopher H
CH
Evans
Gary S
GS
Gruen
D000256:Adenoviridae; D000818:Animals; D001284:Atrophy; D005240:Feasibility Studies; D017102:Fracture Healing; D005599:Fractures, Ununited; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D011817:Rabbits