Abstract

While several studies investigated the effects of mechanical or electrical stimulation on osseointegration and bone fracture healing, little is known about the molecular and cellular impact of combined biophysical stimulation on peri-implant osseointegration. Therefore, we established an in vitro system, capable of applying shear stress and electric fields simultaneously. Capacitively coupled electric fields were used for electrical stimulation, while roughened Ti6Al4V bodies conducted harmonically oscillating micromotions on collagen scaffolds seeded with human osteoblasts. Different variations of single and combined stimulation were applied for three days, while samples loaded with Ti6Al4V bodies and untreated samples served as control. Metabolic activity, expression of osteogenic markers and bone remodeling markers were investigated. While combined stimulation showed no substantial benefit compared to sole mechanical stimulation, we observed that 25 µm micromotions applied by roughened Ti6Al4V bodies led to a significant increase in gene expression of osteocalcin and tissue inhibitor of metalloprotease 1. Additionally, we found an increase in metabolic activity and expression of bone remodeling markers with reduced procollagen type 1 synthesis after 100 mVRMS electrical stimulation. We were able to trigger specific cellular behaviors using different biophysical stimuli. In future studies, different variations of electrical stimulation will be combined with interfacial micromotions.

Highlights

  • Between 2019 and 2050, the number of persons aged 65 or over globally is projected to more than double, indicating that by 2050 one in every four persons in Europe and Northern America could be aged 65 years or over [1]

  • With micromotions and osteoblasts treated with titanium and electrical stimulation (Load + electrical stimulation stimulation (ES)).cells

  • Our results show that metabolic activity, protein synthesis, and gene expression can be significantly influenced by the application of low capacitively coupled electric fields

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Summary

Introduction

Between 2019 and 2050, the number of persons aged 65 or over globally is projected to more than double, indicating that by 2050 one in every four persons in Europe and Northern America could be aged 65 years or over [1]. Following the higher numbers of elderly people, the demand for regenerative medicine is increasing. This applies especially to medical implants, which can be required for various therapeutic indications such as knee and hip replacement and dentures. Pilz et al estimated the number of primary hip replacements performed in Germany in 2040 to grow by 27% from 2010, while projection counts were highest for patients aged 60–70 years [2]. Crucial for fast functionality, long-term stability, and the survival result of the implants is a process called osseointegration

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