Abstract
Simple SummaryPulsed electromagnetic fields (PEMFs) are a type of biophysical stimulation that has been shown to be effective in improving bone regeneration and preventing bone loss. Their use dates back to the 1970s, but a gold standard treatment protocol has not yet been defined. PEMF efficacy relies on the generation of biopotentials, which activate several molecular pathways. There is currently no clear understanding of the effects on bone healing and, in addition, there are several animal models relevant to this issue. Therefore, drawing guidelines and conclusions from the analysis of the studies is difficult. In vivo investigations on PEMF stimulation are reviewed in this paper, focusing on molecular and morphological improvements in bone. Currently, there is little knowledge about the biological mechanism of PEMF and its effect on bone healing. This is due to the variability of crucial characteristics of electro-magnetic fields, such as amplitude and exposure frequency, which may influence the type of biological response. Furthermore, a different responsiveness of cells involved in the bone healing process is documented. Heterogeneous setting parameters and different outcome measures are considered in various animal models. Therefore, achieving comparable results is difficult.Biophysical energies are a versatile tool to stimulate tissues by generating biopotentials. In particular, pulsed electromagnetic field (PEMF) stimulation has intrigued researchers since the 1970s. To date, many investigations have been carried out in vivo, but a gold standard treatment protocol has not yet been defined. The main obstacles are represented by the complex setting of PEMF characteristics, the variety of animal models (including direct and indirect bone damage) and the lack of a complete understanding of the molecular pathways involved. In the present review the main studies about PEMF stimulation in animal models with bone impairment were reviewed. PEMF signal characteristics were investigated, as well as their effect on molecular pathways and osseous morphological features. We believe that this review might be a useful starting point for a prospective study in a clinical setting. Consistent evidence from the literature suggests a potential beneficial role of PEMF in clinical practice. Nevertheless, the wide variability of selected parameters (frequency, duration, and amplitude) and the heterogeneity of applied protocols make it difficult to draw certain conclusions about PEMF effectiveness in clinical implementation to promote bone healing. Deepening the knowledge regarding the most consistent results reported in literature to date, we believe that this review may be a useful starting point to propose standardized experimental guidelines. This might provide a solid base for further controlled trials, to investigate PEMF efficacy in bone damage conditions during routine clinical practice.
Highlights
The effect of pulsed electromagnetic field (PEMF) has been mainly studied in relation to direct trauma models and indirect trauma models
It was interesting to notice in the earliest studies regarding osseous healing and PEMF stimulation, the damage was commonly an osteotomic one
Other researchers tried to explore the effect of PEMF on bone healing in the same animal, treating one limb and using the contralateral as a control
Summary
Maxillofacial surgery, orthopedics, hand surgery, and neurosurgery are some of multidisciplinary research activities in medicine interested in understanding the mechanism of bone healing and, most of all, if it can be accelerated or improved [1–7].The discovery of electrical phenomena related to bone tissue has lead, during the last 50 years, to an exponential increase in both in vitro, in vivo and clinical experimentation, aimed at understanding the application potential of electrical and mechanical energies: to accelerate the healing of fractures, prevent osteoporosis, reduce resorption, accelerate metaphyseal growth, direct differentiation, stimulate cell division etc., [8].The idea of stimulating bone repair through the application of different types of biophysical energies (electrical, electromagnetic, mechanical) arises from several experimental observations: • Bone adapts its shape according to the applied load; this principle is known as Wolff’s law, from the name of the German doctor Julius Wolff who, at the end of the 1800s, described how bone tissue can respond to mechanical load [9]. • It is possible to measure electric potentials on bones in vivo, defined as “biopotentials”, that reflect the metabolic activity of bone itself, these potentials are higher at the metaphyseal level with respect to the diaphyseal one [10,11]. • Bone, when deformed, generates voltage differences due to piezoelectric properties and/or streaming potentials (related to the movement of biological fluids within bone) [8,12,13]. • In case of fracture, a lesion current can be recorded at the fracture site and the whole biopotential distribution of that bone becomes more negative [2]. Taken together, these data indicate that there is a close relationship between the biological activity of bone tissue, mechanical forces (e.g., applied load) and electrical currents. Many types of energies have been applied so far in preclinical research in order to understand their interaction with bone. Among the methods used to transmit biophysical energy to biological systems, there is the faradic system, also known as direct current (DC) application through electrodes directly implanted in bone tissue. This system is invasive, increases the risk of infections, requires a surgical intervention and manifested problems related to the electrochemical reactions around electrodes [14]. Therefore, capacitive coupling (CC) systems have been developed, as they are less invasive. They exploit the electrical field generated between two plates placed externally to the limb where a lesion has to be treated [15–17]. Mechanical stimulation can be delivered through low intensity pulsed ultra sound (LIPUS). This system is based on the properties of piezoelectric crystals that can generate mechanical waves that are applied to tissues when excited with an alternating current at a certain frequency. The search for the optimal signal characteristics lead to the development of clinical devices approved by the FDA in 1994 [18–20]. Nonetheless, recently the role of LIPUS on bone healing has been strongly criticized [21]. Finally, pulsed electromagnetic fields (PEMFs) represent a biophysical stimulation modality that allows the induction of an electric current and a magnetic field in the tissues in a non-invasive way through the application of Helmoltz coils. They can be applied only in a specific area of the body or a total body stimulation can be performed (especially in case of small experimental animal models, like mice or rats).
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