Influence of Low-Magnitude High-Frequency Vibration on Bone Cells and Bone Regeneration

Abstract

Bone is a mechanosensitive tissue for which mechanical stimuli are crucial in maintaining its structure and function. Bone cells react to their biomechanical environment by activating molecular signaling pathways, which regulate their proliferation, differentiation, and matrix production. Bone implants influence the mechanical conditions in the adjacent bone tissue. Optimizing their mechanical properties can support bone regeneration. Furthermore, external biomechanical stimulation can be applied to improve implant osseointegration and accelerate bone regeneration. One promising anabolic therapy is vertical whole-body low-magnitude high-frequency vibration (LMHFV). This form of vibration is currently extensively investigated to serve as an easyto-apply, cost-effective, and efficient treatment for bone disorders and regeneration. This review aims to provide an overview of LMHFV effects on bone cells in vitro and on implant integration and bone fracture healing in vivo. In particular, we review the current knowledge on cellular signaling pathways which are influenced by LMHFV within bone tissue. Most of the in vitro experiments showed that LMHFV is able to enhance mesenchymal stem cell (MSC) and osteoblast proliferation. Furthermore, osteogenic differentiation of MSCs and osteoblasts was shown to be accelerated by LMHFV, whereas osteoclastogenic differentiation was inhibited. Furthermore, LMHFV increased bone regeneration during osteoporotic fracture healing and osseointegration of orthopedic implants. Important mechanosensitive pathways mediating the effects of LMHFV might be the Wnt/beta-catenin signaling pathway, the estrogen receptor (ER) signaling pathway, and cytoskeletal remodeling.

Biophysical Stimuli as the Fourth Pillar of Bone Tissue Engineering

“…Cashion et al revealed that microvibration with a low frequency (1 Hz) induces chondrogenesis, whereas relatively high frequency (100 Hz) promotes osteogenesis ( Cashion et al, 2014 ). Thus, low-magnitude high-frequency vibration (LMHFV) (magnitude < 1 g, frequency 20–90 Hz) is generally used for osteogenesis ( Steppe et al, 2020 ). 50 Hz LMHFVs with different magnitudes (0.1, 0.3, 0.6, and 0.9 g) were used to stimulate PDLCs, and it was found that all groups promote osteogenic differentiation, but LMHFV with 0.3 g peaks the osteoinduction ( Zhang et al, 2015 ).…”

“…Postoperative biophysical stimuli loading strategies are those methods that use noninvasive methods to generate biophysical stimuli to stimulate bone regeneration after surgery, including distraction osteogenesis (DO) ( Shah et al, 2021 ), LMHFV ( Steppe et al, 2020 ), LIPUS ( Hannemann et al, 2014 ), and PEMF ( Wang et al, 2019 ). These strategies have been clinically used to promote the healing of fractures; thus, their use can be extended to the treatment of critical bone defects.…”

Effects of Extracellular Osteoanabolic Agents on the Endogenous Response of Osteoblastic Cells

“…It has been reported that androgen receptor disruption increases the osteogenic response to mechanical loading in male mice [176], while estrogen receptor beta regulates mechanical loading in primary osteoblasts [177]. More importantly, estrogen levels may also influence whether vibrations, loading and mechanical strain generate an anabolic effect on bone cells or not [124,125,127,178,179].…”

The future of basic science in orthopaedics and traumatology: Cassandra or Prometheus?

“…However, if these stimuli become abnormal they can prevent restoration and rather aggravate the disease. Current topics of interest within experimental orthopaedic biomechanics include mechanical testing of normal and diseased musculoskeletal tissues [ 62 , 63 ], medical implant design and testing [ 64 ], tissue engineering [ 65 – 67 ] and translation of biomechanical into biochemical signals [ 68 – 71 ]. This research area will further optimize the biomechanical parameters of tissue-engineered implants and better understand cell- and drug-based therapeutic effects on mechanical behaviour at the tissue-level.…”

“…The role of extracellular matrix in instructing biochemical cascades in cells has become rather evident [ 74 , 75 ]. Also, materials that can closely mimic natural tissue properties and can navigate stem cell fates or exert immunomodulatory features are considered cutting edge [ 71 ]. The progress in developing such next generation biomaterials, that embrace the three-dimensional complexity of regenerating tissues as well as the interplay and optimal integration into the host tissue, can revolutionize biomaterial strategies in the near future.…”