Regenerating Critical Size Rat Segmental Bone Defects with a Self‐Healing Hybrid Nanocomposite Hydrogel: Effect of Bone Condition and BMP‐2 Incorporation

The aim of the current study is to assess the biological performance of self‐healing hydrogels based on calcium phosphate (CaP) nanoparticles and bisphosphonate (BP) conjugated hyaluronan (HA) in a critical size segmental femoral bone defect model in rats. Additionally, these hydrogels are loaded with bone morphogenetic protein 2 (BMP‐2) and their performance is compared in healthy and osteoporotic bone conditions. Treatment groups comprise internal plate fixation and placement of a PTFE tube containing hydrogel (HABP‐CaP) or hydrogel loaded with BMP‐2 in two dosages (HABP‐CaP‐lowBMP2 or HABP‐CaP‐highBMP2). Twelve weeks after bone defect surgery, bone formation is analyzed by X‐ray examination, micro‐CT analysis, and histomorphometry. The data show that critical size, segmental femoral bone defects cannot be healed with HABP‐CaP gel alone. Loading of the HABP‐CaP gel with low dose BMP‐2 significantly improve bone formation and resulted in defect bridging in 100% of the defects. Alternatively, high dose BMP‐2 loading of the HABP‐CaP gel does not improve bone formation within the defect area, but leads to excessive bone formation outside the defect area. Bone defect healing is not affected by osteoporotic bone conditions. This study shows that large size bone defects can heal using calcium phosphate and bisphosphonate conjugated hyaluronan gel with a low dose of bone morphogenetic protein 2 (BMP‐2). Alternatively, if the gel does not contain BMP‐2 or if the dose is high, bone formation is not improved. Bone defect healing is not negatively affected by osteoporotic bone conditions, except when using high dose BMP‐2.