Composite biodegradable formulation promotes bone regeneration in diabetics
Diabetes mellitus (DM) impairs the healing of fractures and there is a need for improved therapeutics to stimulate bone regeneration in diabetic patients. Fracture healing impairment due to DM can be addressed by combining non-viral gene delivery of plasmids independently encoding bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2), which has been demonstrated to act synergistically in promoting fracture healing in a DM animal model. Both insulin and vitamin D3 (VD3) have been independently shown to play key roles in regulating bone fracture healing in DM.
The aim of this study was to investigate if the local delivery of BMP-2 and FGF-2 genes, insulin (INS) and VD3 together could promote bone formation ectopically in Type-2 diabetic rats. A composite consisting of VD3 and insulin containing poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) embedded in a fibrin gel surrounded by a collagen scaffold impregnated with polyethylenimine (PEI)-(pBMP-2+pFGF-2) nanoplexes was developed. Using an osteoinduction model, this study demonstrated that local delivery of INS, VD3 and PEI-(pBMP-2+pFGF-2) resulted in a significant improvement in bone generation compared to other treatments. This study implicates that the combined local release of INS, VD3 and PEI-(pBMP-2 + pFGF-2) may be beneficial for promoting bone regeneration in patients with DM.