The Effect of Poloxamer 407-Based Hydrogel on the Osteoinductivity of Demineralized Bone Matrix

Bone fusion surgery is required for the surgical treatment of degenerative spinal diseases, bone fractures, and tumors. To date, autogenous bone has been considered the most ideal bone graft for bone fusion. However, due to its quantitative limits and donor site morbidity,1) the usage of autogenous bone is gradually decreasing, and various bone graft substitutes have been developed. Bioactive ceramics such as hydroxyapatite, tricalcium phosphate, and calcium pyrophosphate are representative bone graft substitutes which are clinically applied to areas such as spine fusion.2,3,4,5,6) While bioactive ceramics have appealing advantages such as mass production and low risk of inflammation and virus infection, they are osteoconductive materials with a negligible level of osteoinductivity, and thus need to be mixed with autogenous bone for application. To complement this limitation, bone morphogenetic proteins (BMPs) with high osteoinductivity have been developed and applied in various areas, including spinal fusion and tibial non-union.7,8) BMPs are gradually replacing autogenous bone grafts, since they are known to facilitate bone healing and improve fusion rate. However, their many advantages are also accompanied by some disadvantages. They are costly, and are known to cause side effects including ectopic bone formation, formation of seroma,9) neuropathy by neuritis, osteolysis, and soft tissue swelling.10) Moreover, the risk of retrograde ejaculation,11) male infertility and malignancy were also recently reported. Thus, the risk of possible side effects is now advised, rather than their usefulness. Due to its osteoinductivity, demineralized bone matrix (DBM) was frequently applied clinically, before BMP was actively used. However, the usage of DBM is also decreasing, since it has significantly lower osteoinductivity than BMP and mainly functions through osteoconductivity. Thus, it cannot be applied for bone fusion by itself.12) Despite the limitations, use of DBM is still advantageous to reduce autogenous bone graft without using BMP, as DBM rarely develops side effects. DBM is provided in a powder form, which is hard to pattern and fix to the right position. Thus, it requires various types of carriers such as calcium sulfate, hydroxyapatite, tricalcium phosphate, carboxymethylcellulose, glycerol, hyaluronic acid, and bovine gelatin. Poloxamer 407 is a tri-block copolymer consisting of a central hydrophobic polypropylene oxide block flanked by two hydrophilic ethylene oxide blocks.13,14) Poloxamer 407 shows thermoreversible properties, forming a gel-like composite at room temperature to facilitate the solubilization of poorly water-soluble drugs, and forming a gel state at body temperature. Poloxamer 407 has been used in the pharmaceutical field because of the properties such as solubilization promotion, stabilization and bio-adhesiveness.14,15) The putty type of DBM with a carrier improves handling during surgery, but effects on osteoinductivity or osteogenesis have not yet been well examined. This study evaluates the effect on osteogenesis of using poloxamer 407-based hydrogel as a carrier, through various in vitro and in vivo experiments.