High doses of BMPs are needed to achieve clinical success in spinal fusion and long bone non-union fractures with currently available devices. We found that BMP6 was less sensitive to endogenous inhibitors. Recently, we discovered that patients blood coagulum could be used as a BMP6 carrier due to high binding affinity to specific blood components. The BMP6 carrier is a whole blood derived coagulum (WBCD) from the peripheral blood which acts as an endogenous biocompatible material (OSTEOGROW). More than 80% of BMP6 added to the full blood remains incorporated, bound mainly to its extracellular matrix components. Pharmacokinetic studies showed that BMP6 is rapidly cleared from the blood of mice and rats after IV dosing. Presence of BMP6 in circulation is minimal after systemic application and BMP6 is not distributed into the deep tissue compartment. No organ accumulation has been detected by immunohistochemistry. Release of BMP6 from the coagulum in in vitro conditions showed slow discharge from the coagulum with a mean residence time of approximately 7 days. In animal models the osteogenic biological activity of newly produced BMP6 was confirmed without inducing inflammation and oedema in the surrounding tissues. In a model of critical size defect of rabbit ulna WBCD containing BMP6 fully re-bridged the bone defect at a significantly accelerated rate as compared to commercial BMP7 containing bone device. We found that WBCD with 50 μg of BMP6 compared to commercially used device with 3.5 mgs of BMP7 was 2 orders of magnitude more potent in in vivo rabbit ulna critical size defect. Clinical grade of BMP6 will be tested clinically in two indications for regeneration of the metaphyseal bone, compartments where BMP2 and BMP7 have not been effective. Safe, affordable and non-toxic BMP6 based autologous carrier OSTEOGROW will promote faster bone healing and reduce the need for secondary interventions.
Disclosure: The authors declared no competing interests. The research leading to these results has received funding from the European Community Seventh Framework Programme [FP7/2007-2013] under grant agreement n HEALTH-F4-2011-279239.