Surface mineralization of Ti6Al4V substrates with calcium apatites for the retention and local delivery of recombinant human bone morphogenetic protein-2

Titanium alloys are prevalently used as orthopedic prosthetics. Inadequate bone–implant interactions can lead to premature prosthetic loosening and implant failure. Localdelivery of osteogenic therapeutics promoting osteointegration of the implant is an attractive strategy to address this clinical challenge. Given the affinity of calciumapatites for bone matrix proteins we hypothesize that titanium alloys surface mineralized with calciumapatites should be explored for the retention and localdelivery of osteogenic recombinanthumanbonemorphogeneticprotein-2 (rhBMP-2). Using a heterogeneous surface nucleation and growth process driven by the gradual pH elevation of an acidic solution of hydroxyapatite via thermal decomposition of urea, Ti6Al4Vsubstrates were surface mineralized with calciumapatite domains exhibiting good affinity for the substrate. The microstructures, size and surface coverage of the mineral domains as a function of the in vitro mineralization conditions were examined by light and scanning electron microscopy and the surfacecalcium ion content quantified. An optimal mineralization condition was identified to rapidly (<10 h) achieve surface mineral coverage far superior to those accomplished by week long incubation in simulated body fluids. In vitro retention–release profiles of rhBMP-2 from the mineralized and unmineralized Ti6Al4V, determined by an enzyme-linked immunosorbent assay, supported a higher degree of retention of rhBMP-2 on the mineralized substrate. The rhBMP-2 retained on the mineralized substrate after 24 h incubation in phosphate-buffered saline remained bioactive, as indicated by its ability to induce osteogenic transdifferentiation of C2C12 myoblasts attached to the substrate. This mineralization technique could also be applied to the surfacemineralization of calciumapatites on dense tantalum and titanium and porous titanium substrates.