Gene combination promotes bone regeneration in diabetic rabbits

In most cases, the human body almost immediately begins repairing itself after a broken bone. However, the body struggles to regrow bone when the fracture is too large in size, the person is older in age, or is suffering from a disease, such as diabetes.

For these people, there may be a solution in sight.

A recent University of Iowa study, led by researchers in the College of Pharmacy, investigated how the genes fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2) can work synergistically to promote bone regeneration from a critical size fracture. This study was published online in the Journal of Controlled Release in January.

Aliasger Salem“This paper showed that there’s a molecular mechanism by which FGF-2 and BMP-2 work together to give you stronger bone-cell differentiation and bone formation. This is the first time this evidence has been shown in a diabetic animal model,” says Aliasger Salem, UI professor in pharmaceutics and translational therapeutics and senior study author.

Researchers investigated the bone regeneration response in diabetic rabbits embedded with collagen scaffolds containing either the growth factor-2 and bone protein-2 combined or each gene separately. Collagen scaffolds are made with the same biodegradable material as bone.

Since diabetic animals and humans struggle to regenerate bone even after a small fracture, the synergy between the two genes was put to the test. Newly-formed bone tissue in the rabbits was assessed for its volume and union rate percentage.

CT scans revealed significantly increased bone volume for defects treated with scaffolds containing both genes combined compared to each gene separately.

There also was a significant increase in the union rate of fracture bones in the combination treatment compared to the group treated with BMP-2. Bony union was considered complete when the bridging bone between both cortices of the defect was observed.

Fracture union was found in seven fractures (64 percent) of the combination group, one fracture (25 percent) of the FGF-2 group, and zero fractures of the BMP-2 group.

Behnoush Khorsand“This gene delivery system was engineered to have low toxicity in bone-like stem cells, bone-marrow stem cells, and normal cells,” says Behnoush Khorsand, a UI doctoral candidate in pharmaceutics and translational therapeutics and first study author. “We observed the potential the cells had to differentiate and form bone-like cells.”

This study demonstrated that scaffolds loaded with FGF-2 and BMP-2 could be an effective way of promoting bone regeneration in patients with diabetes.

“Our system, which regenerates bone using a novel gene delivery system, had better union rates than the clinical autograph approach,” Khorsand says.

In future studies, the UI team intends to evaluate whether the sequence of delivery of both genes can be used to optimize the level of new bone formed and examine the optimal ratio between these two genes.

In addition to Salem and Khorsand, the UI research team included Satheesh Elangovan, Liu Hong, Douglas Fredericks, Brian Guetschow, Emily Petersen, James Martin, John Femino, Anh-Vu Do, and Nate Nicholson. The study was funded by grants from the American Orthopaedic Foot and Ankle Society and the Lyle and Sharon Bighley Professorship.

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