Concentration‐dependent effects of latex F1 ‐protein fraction incorporated into deproteinized bovine bone and biphasic calcium phosphate on the repair of critical‐size bone defects

F1‐protein fraction (F1) is a natural bioactive compound extracted from the rubber tree, Hevea brasiliensis , and has been recently studied for its therapeutic potential in wound healing. In this study, we investigated the concentration‐dependent effects of F1 (0.01%, 0.025%, 0.05%, and 0.1%) incorporated into deproteinized bovine bone (DBB) and porous biphasic calcium phosphate (pBCP), on the repair of rat calvarial critical‐size bone defects (CSBD). The defects were analyzed by 3D‐microtomography and 2D‐histomorphometry at 12 weeks postsurgery. The binding efficiency of F1 to pBCP (96.3 ± 1.4%) was higher than that to DBB (67.7 ± 3.3%). In vivo analysis showed a higher bone volume (BV) gain in all defects treated with DBB (except in 0.1% of F1) and pBCP (except in 0.05% and 0.1% of F1) compared to the CSBD without treatment/control group (9.96 ± 2.8 mm 3 ). DBB plus 0.025% F1 promoted the highest BV gain (29.7 ± 2.2 mm 3 , p < .0001) compared to DBB without F1 and DBB plus 0.01% and 0.1% of F1. In the pBCP group, incorporation of F1 did not promote bone gain when compared to pBCP without F1 (15.9 ± 4.2 mm 3 , p > .05). Additionally, a small BV occurred in defects treated with pBCP plus 0.1% F1 (10.4 ± 1.4 mm 3, p < .05). In conclusion, F1 showed a higher bone formation potential in combination with DBB than with pBCP, in a concentration‐dependent manner. Incorporation of 0.25% F1 into DBB showed the best results with respect to bone formation/repair in CSBD. These results suggest that DBB plus 0.25% F1 can be used as a promising bioactive material for application in bone tissue engineering.