Otis Singleton
Electrical stimulation (EStim) has been shown to promote bone healing and regeneration in both animal experiments and clinical treatments. Bone stimulators are used to encourage a healing response by activating a pathway that releases chemicals within the body. The role of electrical stimuli in directing cellular activities during the natural tissue healing and regeneration process has been well recognized. This has led to the development and use of exogenous electrical stimulations in the treatment of delayed unions and non-unions of bone fractures.
| Characteristics | Values |
|---|---|
| Purpose | To promote bone healing and regeneration |
| Use cases | Treatment of delayed unions and non-unions of bone fracture |
| Types of stimulators | Direct current, pulsed electromagnetic field, capacitive coupling, inductive coupling |
| Mechanism of action | Increase in intracellular calcium stores, which activates calmodulin and promotes cellular proliferation in bone |
| Bone formation | Increase in osteoblasts and decrease in osteoclasts |
| Bone growth factors | BMP-2, TGF-β1, insulin growth factor-2 |
| Efficacy | Moderate evidence of improved pain relief, but no significant difference in functional outcomes |
| Limitations | High cost, lack of faith in efficacy by clinicians, inconsistent and inconclusive clinical evidence |
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What You'll Learn
Bone tissue engineering (BTE)
Electrical stimulation (EStim) has been shown to promote bone healing and regeneration in both animal experiments and clinical treatments. Recent studies have demonstrated EStim's positive osteogenic effects at the cellular and molecular levels, providing intriguing clues to the underlying mechanisms by which it promotes bone healing. For example, in vitro studies have shown that EStim enhances bone healing by changing growth factors and transmembrane signalling. Specifically, EStim increases intracellular calcium stores, which activate the last step in the pathway of enhancing activated calmodulin levels, which has been shown to promote cellular proliferation in bone.
In most in vitro applications, cells grown in 2-D or 3-D culture can be treated with specific regimens of EStim in purpose-built chambers. EStim devices for use in treating ex vivo cells prior to transplantation will have to be developed, while commercially available DC bone growth stimulators could be adapted for treating transplanted BTE constructs in clinical settings.
The goal of current BTE research is to develop combinations of cells, scaffolds, and chemical and physical stimuli that optimise treatment outcomes. Incorporating EStim into promising new BTE therapies is a logical next step. However, better-designed clinical studies will enable the optimisation of EStim for clinical practice.
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Direct current electrical stimulation
A second faradic product, hydrogen peroxide, is also formed at the cathode. This enhances osteoclast differentiation, triggering bone formation by osteoblasts. Hydrogen peroxide may also stimulate macrophages to release vascular endothelial growth factor (VEGF), which is critical for fracture healing.
Invasive direct current electrical stimulation devices require the surgical implantation of a current generator in an intramuscular or subcutaneous space. The implantable device typically remains functional for 6 to 9 months, after which a second surgical procedure is needed to remove the current generator.
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Capacitive coupling
In vitro studies have shown that capacitive coupling stimulates bone formation by increasing calcium translocation via voltage-gated calcium channels. This process triggers an augmenting pathway, beginning with an increase in phospholipase A2, which raises prostaglandin E2 synthesis. This amplifies cystolic Ca2+, increasing intracellular calcium stores and activating the final step in the pathway: enhancing activated calmodulin levels.
Overall, capacitive coupling is a promising method for enhancing bone healing, particularly in the case of non-unions. However, further clinical studies are required to optimise this treatment for clinical practice.
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Inductive coupling
Electrical stimulation (ES) has been used to promote bone healing and regeneration in animal experiments and clinical treatments. However, the clinical efficacy and safety of these exogenous electrical stimulation methods are argued to be inconsistent and inconclusive due to a lack of well-controlled, randomised clinical studies.
The size of the induced electrical field within the fracture site depends on the strength of the magnetic field and the physical characteristics of the tissue. This method of electrical stimulation is also known as pulsed electromagnetic field (PEMF) therapy. As of 2018, there were 9 FDA-approved electrical bone growth stimulators (EBGS) that were commercially available for the treatment of spinal fusion and fracture nonunion.
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Bone stimulators
The goal of bone stimulators is to activate a series of receptors in the body that encourage a healing response. This activation process triggers a pathway that releases chemicals, or signals, within the body to promote fracture healing. This process is known as a "cascade," where one signal stimulates another process, creating a chain reaction until healing is complete.
While bone stimulators have shown promising results in certain cases, they are not yet widely used in clinical practice. The high cost and skepticism among clinicians about their efficacy have hindered their adoption. Additionally, there is a lack of well-controlled, randomized clinical studies to conclusively prove their effectiveness. As a result, researchers are exploring the development of smart biomaterials that can generate in situ electrical stimuli to accelerate bone repair and regeneration.
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Frequently asked questions
Electrical stimulation (EStim) is a treatment method that uses electricity to promote bone healing and regeneration.
Electrical stimulation activates a pathway that releases chemicals within the body. These chemicals act as signals that trigger a "cascade", a process where one signal stimulates another process, and so on until the bone is healed.
Examples of electrical stimulation treatments include direct current, pulsed electromagnetic field, and capacitive coupling.
Electrical stimulation has been shown to be effective in enhancing bone healing in spinal fusion and treating nonunions. It can also be used as an adjunct for the promotion of bone healing in ankle surgery.
One drawback is that electrical stimulation is not commonly used in clinical practice due to its high cost and lack of faith in its efficacy by clinicians. Additionally, there is a lack of sufficient well-controlled, randomized clinical studies to conclusively prove the clinical efficacy and safety of electrical stimulation methods.
