A Novel PTH-Related Peptide Combined with 3d Printed Macroporous Titanium Alloy Scaffold Enhances Osteoporotic Osseointegration.

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. We designed 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. In vitro, PTHrP-2 enhanced the proliferation, adhesion, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) within the mTAS. Furthermore, it promoted 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 safeguarded the proliferation and migration of BMSCs and HUVECs, reduced reactive oxygen species generation and mitochondrial damage, and partially preserved the angiogenesis of HUVECs. In the Sprague-Dawley (SD) rat osteoporosis model, we compared 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. The results demonstrated that mTAS P2 exhibited a high bone growth rate and 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. This article is protected by copyright. All rights reserved.