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Physical Stimulations for Bone and Cartilage Regeneration

  • Xiaobin Huang
  • Ritopa Das
  • Avi Patel
  • Thanh Duc Nguyen
Review Paper
  • 46 Downloads

Abstract

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.

Keywords

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

Abbreviations

GBR

guided bone regeneration

ACI

autologous chondrocyte implantation

hMSCs

human mesenchymal stem cells

ECM

extracellular matrix

ASCs

mouse adipose-derived mesenchymal stem cells

PFF

pulsating fluid flow

OPN

osteopontin

SSAT

spermidine/spermine-N(1)-acetyltransferase

FAK

focal adhesion kinase

RhoA

Ras homolog gene family member A

VSCC

voltage-sensitive calcium channels

ES

electrical stimulation

EF

electric field

DC

direct current

CCEF

capacitive coupling electric field

EMF

electromagnetic field

AC

alternating current

PI3K

phosphatidylinositol-3-kinase

mTOR

mammalian target of rapamycin

TGF-β

transforming growth factor-β

A2AR

adenosine A2A receptors

GAGs

glycosaminoglycans

PEMFs

pulsed electromagnetic fields

ELF-PEMF

extremely low-frequency pulsed electromagnetic field

ROS

reactive oxygen species

Col I

collagen type I

GSK-3β

glycogen synthase kinase-3 beta

TRK

tyrosine kinase receptor

TCF/LEF

T cell factor/lymphoid enhancer factor

PI3K

phosphatidylinositide 3-kinases

TGF-β

transforming growth factor beta

BMP

bone morphogenetic proteins

AKT

protein kinase B

mTOR

mechanistic target of rapamycin

NF-κB

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

PGE2

prostaglandin E2

AC

adenylyl cyclase

cAMP

cyclic adenosine monophosphate

PKA

protein kinase A

CREB

cAMP response element-binding protein

PKC

protein kinase C

MAPK

mitogen-activated protein kinase

ERK

extracellular signal-regulated kinases

FAK

focal adhesion kinase

GPCR

G protein-coupled receptor

OCN

osteocalcin

Osx

osterix

US

ultrasound

LIPUS

low-intensity pulsed ultrasound

BSP

bone sialoprotein

MCP

monocyte-chemoattractant protein

MIP

macrophage-inflammatory protein

RANKL

receptor activator of nuclear factor kappa-Β ligand

ATI

angiotensin II type I receptor

NO

nitric oxide

PGE2

prostaglandin E2

VEGF

vascular endothelial growth factor

GPCRs

G protein-coupled receptors

BMSCs

bone marrow-derived mesenchymal stem cells

ESWT

extracorporeal shock wave therapy

CBFA1

core-binding factor alpha1

ROCK

RhoA and Rho-associated protein kinase

PG

proteoglycan

ACAN

aggrecan

PRG4

proteoglycan 4

SZP

superficial zone protein

PCM

pericellular matrix

TRPV4

transient receptor potential vanilloid 4

CC

capacitive coupling

EPAC

exchange proteins activated directly by cyclic AMP

TNF-α

tumor necrosis factor-α

NF-AT

nuclear factor of activated T cells

SMFs

static magnetic fields

WOMAC

Western Ontario and McMaster University Osteoarthritis Index

LLLT

low-level laser therapy

Notes

Funding Information

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

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© The Regenerative Engineering Society 2018

Authors and Affiliations

  • Xiaobin Huang
    • 1
  • Ritopa Das
    • 1
  • Avi Patel
    • 1
  • Thanh Duc Nguyen
    • 1
  1. 1.University of ConnecticutStorrsUSA

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