Figure5. Combined BMP2 treatment and MEK improves bone healing in Nf1_osx^−/− mice.

(a-g) Following tibia fracture, WT an Nf1osx^−/− mice were treated (Tx) with vehicle (nanoparticles and polyglycidol) or rBMP2-polyglycidol or Trametinib nanoparticles or both, 1 and 7 days post fracture. (a) Treatment scheme. (b-f) 3D μCT representative reconstruction images (b), quantification of callus bone volume (BV, c); callus tissue volume (TV, d); callus bone volume over total volume (BV/TV, e) and callus tissue mineral density (TMD, f) in WT and Nf1_Osx^−/− mice 21 days after fracture. (g-h) Callus strength (maximum peak force, f) and callus stiffness (h) measured by three-point bending tests were significantly lower in Nf1_Osx^−/− mice compared to WT mice,21 DPF. *:p<0.05 versus WT, #:p<0.05 versus single treatment in theNf1_Osx^−/− mouse group (n=10-15 mice/group).