Improvement in the delivery system of bone morphogenetic protein-2: a new approach to promote bone formation.

Much research has been focused on developing bone morphogenetic protein-2(BMP-2) delivery systems to enhance bone formation in bone defect repair and bone tissue engineering. However, many of these current systems have several drawbacks associated with low loading efficiencies and reduced biological activities after release. Collagen scaffolds can be used as in delivery systems because of their biocompatibility. However, growth factors have naturally low affinity to collagen, which is disadvantageous for maintaining a sufficient growth factor concentration at the delivery sites. To enhance BMP-2 binding to collagen scaffolds, we chose a porous collagen scaffold that was chemically modified using Traut's reagent. The modified collagen scaffold allows cross-linking of the collagen fibers and is able to immobilize more BMP-2 after treatment with Sulfo-SMCC. We demonstrated that cross-linking led to a slower release rate of BMP-2, but did not reduce its biological activity. Moreover, more ectopic bone formation was induced by subcutaneous implants of cross-linked collagen treated with BMP-2. We concluded that collagen scaffolds chemically conjugated with BMP-2 using Traut's reagent and Sulfo-SMCC was an effective delivery system for use in bone defect repair and in bone tissue engineering.