The goal of this study was to determine the effectiveness of using polyethyleneimine (PEI) and a polyethylene glycol (PEG) tether to bind human recombinant bone morphogenetic protein‐2 (rhBMP‐2) to hydroxyapatite (HAp) to enhance rhBMP‐2 loading, alter its release properties, and enhance cellular interaction with the material. By using a branched PEI that was derived to express free thiols, rhBMP‐2 was coated onto dense HAp surfaces at ∼43 ng/cm2. Using this novel attachment methodology, it was observed that the PEI‐SH coating did not change the morphology of the HAp surfaces and that the amount of rhBMP‐2 loaded was comparable to a direct adsorption method. In addition, it was also observed that the PEI and PEG tether significantly retained the rhBMP‐2 to the HAp surface, inhibiting the burst release effect. Using human fetal osteoblast cells, the PEI‐ and PEG‐tethered BMP‐2 was also observed to increase cellular attachment by 10‐fold when compared with uncoated HAp and adsorbed rhBMP‐2. It was concluded from this study that PEI and PEG tether significantly reduce the initial burst release effect of rhBMP‐2. It was also concluded that the rhBMP‐2 conjugation to PEI and PEG tether promoted an increase in cellular attachment to the HAp surface. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:3117–3123, 2012.

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