Evaluation of Ad‐BMP‐2 for enhancing fracture healing in an infected defect fracture rabbit model

The objective of this study was to evaluate the use of adenoviral transfer of the BMP‐2 gene (Ad‐BMP‐2) for enhancing healing in an infected defect fracture model. A femoral defect stabilized with plates and screws was surgically created in sixty‐four skeletally mature New Zealand white rabbits. Experimental groups were: (1) non‐infected Ad‐luciferase (Ad‐LUC, NONLUC), (2) non‐infected Ad‐BMP‐2 (NONBMP), (3) infected Ad‐LUC (INFLUC), and (4) infected Ad‐BMP‐2 (INFBMP). A sclerosing agent was applied to the ends of the bone at surgery to facilitate the development of osteomyelitis. Fracture healing was evaluated radio‐graphically and histologically. Data were analyzed using an ANOVA, with statistical significance set as p < 0.05.

[1]  E. E. Johnson,et al.  One-stage lengthening of femoral nonunion augmented with human bone morphogenetic protein. , 1998, Clinical orthopaedics and related research.

[2]  Christian Lattermann,et al.  A gene therapy approach to accelerating bone healing Evaluation of gene expression in a New Zealand white rabbit model , 1999, Knee Surgery, Sports Traumatology, Arthroscopy.

[3]  K. Jain.  Textbook of Gene Therapy , 1998 .

[4]  K. Chihara,et al.  Stimulatory effect of bone morphogenetic protein‐2 on osteoclast‐like cell formation and bone‐resorbing activity , 1995, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[5]  M. Longaker,et al.  Expression of Adenovirally Delivered Gene Products in Healing Osseous Tissues , 2000, Annals of plastic surgery.

[6]  J. Heckman,et al.  Bone morphogenetic protein but not transforming growth factor-beta enhances bone formation in canine diaphyseal nonunions implanted with a biodegradable composite polymer. , 1999, The Journal of bone and joint surgery. American volume.

[7]  M. Longaker,et al.  Adenovirus‐Mediated Gene Therapy of Osteoblasts In Vitro and In Vivo , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[8]  T. Yoneda,et al.  Patterns of gene expression associated with BMP-2-induced osteoblast and adipocyte differentiation of mesenchymal progenitor cell 3T3-F442A , 2000, Journal of Bone and Mineral Metabolism.

[9]  P. Robbins,et al.  Genetic enhancement of fracture repair: healing of an experimental segmental defect by adenoviral transfer of the BMP-2 gene , 2000, Gene Therapy.

[10]  L. Sandell.  Genes and gene expression. , 2000, Clinical orthopaedics and related research.

[11]  H. Burtscher,et al.  BMP-2 and sonic hedgehog have contrary effects on adipocyte-like differentiation of C3H10T1/2 cells. , 2000, DNA and cell biology.

[12]  W. Lew,et al.  Osteogenic protein‐1 induced bone formation in an infected segmental defect in the rat femur , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[13]  R Krauspe,et al.  Potential role of direct adenoviral gene transfer in enhancing fracture repair. , 2000, Clinical orthopaedics and related research.

[14]  C. Kawcak,et al.  Evaluation of serum biochemical markers of bone metabolism for early diagnosis of nonunion and infected nonunion fractures in rabbits. , 2003, American journal of veterinary research.

[15]  John C. Lee,et al.  Osteogenic protein-1 increases gene expression of vascular endothelial growth factor in primary cultures of fetal rat calvaria cells , 1999, Molecular and Cellular Endocrinology.

[16]  S. Goldstein,et al.  Potential Role for Direct Gene Transfer in the Enhancement of Fracture Healing , 1998, Clinical orthopaedics and related research.

[17]  J. Wozney,et al.  Bone Morphogenetic Protein-2 Increases the Rate of Callus Formation after Fracture of the Rabbit Tibia , 1999, Calcified Tissue International.

[18]  V. Rosen,et al.  The healing of segmental bone defects, induced by recombinant human bone morphogenetic protein (rhBMP-2). A radiographic, histological, and biomechanical study in rats. , 1992, The Journal of bone and joint surgery. American volume.

[19]  E. Wang,et al.  Bone morphogenetic protein-2 causes commitment and differentiation in C3H10T1/2 and 3T3 cells. , 1993, Growth factors.

[20]  G. Finerman,et al.  Regional gene therapy with a BMP‐2‐producing murine stromal cell line induces heterotopic and orthotopic bone formation in rodents , 1998, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.