Biophysical stimulation of bone fracture repair, regeneration and remodelling.

Abstract

Biophysical stimulation to enhance bone fracture repair and bone regenerate maturation to restore its structural strength must rely on both the biological and biomechanical principle according to the local tissue environment and the type of mechanical stress to be born by the skeletal joint system. This paper reviews the possible interactions between biophysical stimuli and cellular responses in healing bone fractures and proceeds to speculate the prospects and limitations of different experimental models in evaluating and optimising such non-invasive interventions. It is important to realize that bone fracture repair has several pathways with various combinations of bone formation mechanisms, but there may only be one bone remodeling principle regulated by the hypothesis proposed by Wolff. There are different mechanical and biophysical stimuli that could provide effective augmentation of fracture healing and bone regenerate maturation. The key requirements of establishing these positive interactions are to define the precise cellular response to the stimulation signal in an in vitro environment and to use well-established animal models to quantify and optimise the therapeutic regimen in a time-dependent manner. This can only be achieved through research collaboration among different disciplines using scientific methodologies. In addition, the specific forms of biophysical stimulation and its dose effect and application timing must be carefully determined and validated. Technological advances in achieving focalized stimulus delivery with adjustable signal type and intensity, in the ability to monitor healing callus mechanical property non-invasively, and in the establishment of a robust knowledgebase to develop effective and reliable treatment protocols are the essential pre-requisites to make biophysical stimulation acceptable in the main arena of health care. Finally, it is important to bear in mind that successful fracture repair or bone regeneration through callus distraction without adequate remodeling process through physiological loading would seriously undermine the value of biophysical stimulation in meeting the biomechanical demand of a long bone.

Bone development and its relation to fracture repair. The role of mesenchymal osteoblasts and surface osteoblasts

“…Efforts were made to harness this phenomenon to hasten bone repair by applying either alternating pulsed electromagnetic fields or lower power direct current to fracture sites (Bassett et al, 1964;Bassett et al, 1982;Brighton, 1981). These methods along with low intensity pulsed ultrasound, extracorporeal shock wave stimulation, and low intensity high frequency vibration, are less frequently used today but the phenomena and the differing ways of application remain attractive for future investigation (Chao and Inoue, 2003).…”

Electrical Stimulation in Tissue Regeneration

“…Of interest is the fact that some of these proteins can be regulated through physical stimulation. Cultured cells and tissues subjected to different biophysical stimuli of varying intensities in both in vitro and in vivo settings have been reviewed (Chao & Inoue, 2003;Wiesmann et al, 2004). These stimuli include mechanical force, electrical and electromagnetic field, laser irradiation, heat shock, and ultrasound.…”

“…Some of them are already applied in the clinical setting to treat tissue defects (Barrere et al, 2008). Studies have shown that osteoprogenitor cells and osteoblasts increased their proliferation and differentiation, as well as the production of ECM and growth and differentiation factors including TGF-and BMPs by EMFs (Chao & Inoue, 2003;Dimitriou & Babis, 2007). Therefore, growth factors regulating bone formation can be endogenously induced through the appropriate extrinsic biophysical stimulation to bone cells.…”

Effects of ultrasound on Transforming Growth Factor-beta genes in bone cells

“…Over the past two decades, a range of alternative techniques that apply a biophysical stimulus to the fracture site, such as therapeutic ultrasound (US) or pulsed electromagnetic fields, have also been shown to accelerate fracture healing (Chao and Inoue, 2003). Such new techniques offer the potential for noninvasive therapies that can accelerate the normal healing process or provide an alternative treatment in cases of abnormal healing such as nonunion or delayed union.…”