COMSOL simulations of BMP-2 release from alginate constructs in femoral defects. BMP-2 release simulations of constructs containing 2.5 μg of BMP-2 in alginate, BMP-2 loaded onto 1 mg of HMPs in alginate, and BMP-2 loaded onto 0.1 mg of HMPs in alginate. Constructs without HMPs and with 1 mg of HMPs were tested in vivo. A) Heat maps after 14 days demonstrated (i) a large spatial gradient of BMP-2 in femurs treated with BMP-2 in alginate, (ii) a minimal spatial gradient of BMP-2 in femurs treated with BMP-2 loaded onto 1 mg of HMPs in alginate, and (iii) a moderate spatial gradient of BMP-2 in femurs treated with BMP-2 loaded onto 0.1 mg of HMPs in alginate. Similarly, graphs of the simulation results revealed (i) an increase the percentage of BMP-2 released into the surrounding tissue and decrease in the percentage of BMP-2 remaining within the alginate in constructs containing BMP-2 alone, (ii) most of the delivered BMP-2 remaining bound to the HMPs over 14 days in constructs containing 1 mg of HMPs, and (iii) a moderate release of BMP-2 into the surrounding tissue and high retention of BMP-2 in the alginate in constructs containing 0.1 mg of HMPs.