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. 2023 Nov;12(29):e2301604.
doi: 10.1002/adhm.202301604. Epub 2023 Aug 24.

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

Junwu Wang  1 , Renxin Chen  1 , Bin Ren  1 , Qinyu Feng  1 , Beihai Li  1 , Zhuowen Hao  1 , Tianhong Chen  1 , Yingkun Hu  1 , Yilong Huang  1 , Qi Zhang  1 , Yi Wang  1 , Jinghuan Huang  2 , Jingfeng Li  1
Affiliations

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

Junwu Wang et al. Adv Healthc Mater. 2023 Nov.

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 (mTASP2 ) and ordinary mTAS implanted for 12 weeks via micro-CT, sequential fluorescent labeling, and histology are compared. The results demonstrate that mTASP2 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.

Keywords: PTH-related peptides; macroporous titanium alloy scaffolds; osseointegration; osteoporosis.

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