Evaluation of fibrin-based gene-activated matrices for BMP2/7 plasmid codelivery in a rat nonunion model.

Abstract

Treatment of large-segmental bone defects still is a challenge in clinical routine. Application of gene-activated matrices (GAMs) based on fibrin, bone morphogenic protein (BMP) 2/7 plasmids and nonviral transfection reagents (cationic polymers) could be an innovative treatment strategy to overcome this problem. The aim of this study was to determine the therapeutic efficacy of fibrin GAMs with or without additional transfection reagents for BMP2 and 7 plasmid codelivery in a femur nonunion rat model. In this experimental study, a critical-sized femoral defect was created in 27 rats. At four weeks after the surgery, animals were separated into four groups and underwent a second operation. Fibrin clots containing BMP2/7 plasmids with and without cationic polymer were implanted into the femoral defect. Fibrin clots containing recombinant human (rh) BMP2 served as positive and clots without supplement as negative controls. At eight weeks, animals that received GAMs containing the cationic polymer and BMP2/7 plasmids showed decreased bone volume compared with animals treated with GAMs and BMP2/7 only. Application of BMP2/7 plasmids in fibrin GAMs without cationic polymer led to variable results. Animals that received rhBMP2 protein showed increased bone volume, and osseous unions were achieved in two of six animals. Cationic polymers decrease therapeutic efficiency of fibrin GAM-based BMP2/7 plasmid codelivery in bone regeneration. Nonviral gene transfer of BMP2/7 plasmids needs alternative promoters (e.g. by sonoporation, electroporation) to produce beneficial clinical effects.