Trace Element-Augmented Titanium Implant With Targeted Angiogenesis and Enhanced Osseointegration in Osteoporotic Rats.

Ran Yan,Longwei Hu,Jinhua Li,Xiangkai Zhang,Jin Wen,Ruixue Jiang,Xinquan Jiang,Qianju Wu,Yuwei Deng

doi:10.3389/fchem.2022.839062

Abstract

Deteriorated bone quality in osteoporosis challenges the success of implants, which are in urgent need for better early osseointegration as well as antibacterial property for long-term stability. As osteoporotic bone formation tangles with angiogenic clues, the relationship between osteogenesis and angiogenesis has been a novel therapy target for osteoporosis. However, few designs of implant coatings take the compromised osteoporotic angiogenic microenvironment into consideration. Here, we investigated the angiogenic effects of bioactive strontium ions of different doses in HUVECs only and in a co-culture system with BMSCs. A proper dose of strontium ions (0.2–1 mM) could enhance the secretion of VEGFA and Ang-1 in HUVECs as well as in the co-culture system with BMSCs, exhibiting potential to create an angiogenic microenvironment in the early stage that would be beneficial to osteogenesis. Based on the dose screening, we fabricated a bioactive titanium surface doped with zinc and different doses of strontium by plasma electrolytic oxidation (PEO), for the establishment of a microenvironment favoring osseointegration for osteoporosis. The dual bioactive elements augmented titanium surfaces induced robust osteogenic differentiation, and enhanced antimicrobial properties. Augmented titanium implant surfaces exhibited improved bone formation and bone–implant contact under comprehensive assessment of an in vivo bone–implant interface. In conclusion, zinc- and strontium-augmented titanium surface benefits the osseointegration in osteoporosis via promoting osteogenic differentiation, exerting antibacterial efficacy, and stimulating early angiogenesis.

Highlights

With a large population and the fast growth of osteoporotic patients, the need for more favorable implants in dentistry and orthopedics is urgent, in that decreased bone mass and deteriorated bone microarchitecture hinder the success of osseointegration at the early stage (Dereka et al, 2018; Liu et al, 2021b)
To identify the role of Sr in the microenvironment around implant sites, it is of significance to first test the direct effects of Sr on osteogenesis and angiogenesis, respectively
To evaluate the osteogenic effects of Sr, human BMSCs (hBMSCs) were cultivated in α medium (α-MEM) containing different doses of Sr for 7 days and tested ALP expression as an early biomarker of osteogenesis through ALP staining

Summary

Introduction

With a large population and the fast growth of osteoporotic patients, the need for more favorable implants in dentistry and orthopedics is urgent, in that decreased bone mass and deteriorated bone microarchitecture hinder the success of osseointegration at the early stage (Dereka et al, 2018; Liu et al, 2021b). Vascularization of ossifying tissue is highly required for bone growth and development while osteoporosis exhibits vascular defects with reduced connection between osteogenesis and angiogenesis (Song et al, 2019; Tong et al, 2019). Improvement of bone angiogenesis has won widespread attention as a novel target in the prevention and treatment of osteoporosis (Sivaraj and Adams, 2016; Fu et al, 2020; Chen et al, 2021). Implants with the function of promoting angiogenesis have potential to create a desirable osseointegration environment in osteoporotic bone (Zhou et al, 2020). It is promising to promote the osteoporotic bone implant niche with compromised angiogenesis and osteogenesis using hierarchical titanium surface with tailored trace elements

Methods

Results

Conclusion