Physical Stimulations for Bone and Cartilage Regeneration


A wide range of techniques and methods are actively invented by clinicians and scientists who are dedicated to the field of musculoskeletal tissue regeneration. Biological, chemical, and physiological factors, which play key roles in musculoskeletal tissue development, have been extensively explored. However, physical stimulation is increasingly showing extreme importance in the processes of osteogenic and chondrogenic differentiation, proliferation and maturation through defined dose parameters including mode, frequency, magnitude, and duration of stimuli. Studies have shown manipulation of physical microenvironment is an indispensable strategy for the repair and regeneration of bone and cartilage, and biophysical cues could profoundly promote their regeneration. In this article, we review recent literature on utilization of physical stimulation, such as mechanical forces (cyclic strain, fluid shear stress, etc.), electrical and magnetic fields, ultrasound, shock waves, and substrate stimuli, to promote the repair and regeneration of bone and cartilage tissue. Emphasis is placed on the mechanism of cellular response and the potential clinical usage of these stimulations for bone and cartilage regeneration.

Lay Summary

Bone and cartilage regenerative engineering aims to create stable, bioactive, and native tissue-like scaffolds which can repair bone and cartilage damages. These scaffolds are often combined with chondrogenic/osteogenic cells or stem cells to create replacement tissue grafts with enhanced regenerative capability. In this approach, physical stimulations such as ultrasound, mechanical force, electrical charge, and magnetic field have significant impacts on cell fate and behavior through regulating various intracellular signaling pathways. The review provides a comprehensive understanding and broad overview of literature on effects of different physical stimulations on cellular behaviors and signaling pathways, which have been reported to induce growth of bone and cartilage. The knowledge lay a strong foundation for the development of future “smart” tissue grafts that can effectively repair bone and cartilage under physical stimulations. Other future works will focus on combining different physical stimulations and fine-tuning parameters of such stimulations to obtain optimal cartilage and bone regeneration.

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Fig. 4



guided bone regeneration


autologous chondrocyte implantation


human mesenchymal stem cells


extracellular matrix


mouse adipose-derived mesenchymal stem cells


pulsating fluid flow






focal adhesion kinase


Ras homolog gene family member A


voltage-sensitive calcium channels


electrical stimulation


electric field


direct current


capacitive coupling electric field


electromagnetic field


alternating current




mammalian target of rapamycin


transforming growth factor-β


adenosine A2A receptors




pulsed electromagnetic fields


extremely low-frequency pulsed electromagnetic field


reactive oxygen species

Col I:

collagen type I


glycogen synthase kinase-3 beta


tyrosine kinase receptor


T cell factor/lymphoid enhancer factor


phosphatidylinositide 3-kinases


transforming growth factor beta


bone morphogenetic proteins


protein kinase B


mechanistic target of rapamycin


nuclear factor kappa-light-chain-enhancer of activated B cells


prostaglandin E2


adenylyl cyclase


cyclic adenosine monophosphate


protein kinase A


cAMP response element-binding protein


protein kinase C


mitogen-activated protein kinase


extracellular signal-regulated kinases


focal adhesion kinase


G protein-coupled receptor








low-intensity pulsed ultrasound


bone sialoprotein


monocyte-chemoattractant protein


macrophage-inflammatory protein


receptor activator of nuclear factor kappa-Β ligand


angiotensin II type I receptor


nitric oxide


prostaglandin E2


vascular endothelial growth factor


G protein-coupled receptors


bone marrow-derived mesenchymal stem cells


extracorporeal shock wave therapy


core-binding factor alpha1


RhoA and Rho-associated protein kinase






proteoglycan 4


superficial zone protein


pericellular matrix


transient receptor potential vanilloid 4


capacitive coupling


exchange proteins activated directly by cyclic AMP


tumor necrosis factor-α


nuclear factor of activated T cells


static magnetic fields


Western Ontario and McMaster University Osteoarthritis Index


low-level laser therapy


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The authors thank NIH for the research support (1R21EB024787).

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Correspondence to Thanh Duc Nguyen.

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Huang, X., Das, R., Patel, A. et al. Physical Stimulations for Bone and Cartilage Regeneration. Regen. Eng. Transl. Med. 4, 216–237 (2018).

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  • Bone and cartilage regeneration
  • Fracture repair
  • Physical stimulation
  • Electrical and magnetic fields
  • Mechanical forces
  • Ultrasound
  • Shock waves