A Novel PTH‐Related Peptide Combined With 3D Printed Macroporous Titanium Alloy Scaffold Enhances Osteoporotic Osseointegration

Abstract Previous parathyroid hormone (PTH)‐related peptides (PTHrPs) cannot be used to prevent implant loosening in osteoporosis patients due to the catabolic effect of local sustained release. A novel PTHrP (PTHrP‐2) that can be used locally to promote osseointegration of macroporous titanium alloy scaffold (mTAS) and counteract implant slippage in osteoporosis patients is designed. In vitro, PTHrP‐2 enhances the proliferation, adhesion, and osteogenic differentiation of bone marrow‐derived mesenchymal stem cells (BMSCs) within the mTAS. Further, it promotes proliferation, migration, angiogenesis‐related protein expression, and angiogenesis in human umbilical vein endothelial cells (HUVECs). Compared to PTH(1–34), PTHrP‐2 can partially weaken the osteoclast differentiation of RAW 264.7 cells. Even in an oxidative stress microenvironment, PTHrP‐2 safeguards the proliferation and migration of BMSCs and HUVECs, reduces reactive oxygen species generation and mitochondrial damage, and partially preserves the angiogenesis of HUVECs. In the Sprague–Dawley (SD) rat osteoporosis model, the therapeutic benefits of PTHrP‐2‐releasing mTAS (mTAS P2 ) and ordinary mTAS implanted for 12 weeks via micro‐CT, sequential fluorescent labeling, and histology are compared. The results demonstrate that mTAS P2 exhibits high bone growth rate, without osteophyte formation. Consequently, PTHrP‐2 exhibits unique local synthesis properties and holds the potential for assisting the osseointegration of alloy implants in osteoporosis patients.