Objective: To investigate whether the burst release of BMP from ACS bioimplants can be minimized through biophysical means and/or combination with excipients.
Methods: Samples were prepared by combining rhBMP-2 impregnated ACS with various excipients (chitosan or Pluronic F127) and by using different BMP application methods (soak, air-dry, lyophilize). Samples were then incubated in PBS+0.1%BSA which was changed after 1, 6, 24, 72, 120, and 168 hours. The amount of BMP released at each time point was measured by ELISA and its corresponding bioactivity was measured using a C2C12-based assay. Data was analyzed by 1 or 2-way ANOVA.
Results: Different application methods in the absence of excipients had no effect on BMP release. Combining the bioimplant with either chitosan or F127 reduced the amount of BMP released compared to control (P=0.019, P<0.001). Lyophilization in combination with excipients further reduced the amount of BMP released (P<0.01). All bioimplant-released BMP was biologically active.
Conclusions: The burst release of BMP from bioimplants can be minimized through the use of excipients and may be further reduced by their use in combination with lyophilization. Thus, it may be possible to reduce the BMP dose and so minimize the risks and cost associated with the current high dosing levels through the use of such excipients.
Funding: University of Toronto Summer Student Program