Electrical stimulation (EStim) has been shown to promote bone healing and regeneration both in animal experiments and clinical treatments. Therefore, incorporating EStim into promising new bone ...tissue engineering (BTE) therapies is a logical next step. The goal of current BTE research is to develop combinations of cells, scaffolds, and chemical and physical stimuli that optimize treatment outcomes. Recent studies demonstrating EStim’s positive osteogenic effects at the cellular and molecular level provide intriguing clues to the underlying mechanisms by which it promotes bone healing. In this review, we discuss results of recent in vitro and in vivo research focused on using EStim to promote bone healing and regeneration and consider possible strategies for its application to improve outcomes in BTE treatments. Technical aspects of exposing cells and tissues to EStim in in vitro and in vivo model systems are also discussed.
Background
Electrical stimulation (EStim) has been proven to promote bone healing in experimental settings and has been used clinically for many years and yet it has not become a mainstream clinical ...treatment.
Methods
To better understand this discrepancy we reviewed 72 animal and 69 clinical studies published between 1978 and 2017, and separately asked 161 orthopedic surgeons worldwide about their awareness, experience, and acceptance of EStim for treating fracture patients.
Results
Of the 72 animal studies, 77% reported positive outcomes, and the most common model, bone, fracture type, and method of administering EStim were dog, tibia, large bone defects, and DC, respectively. Of the 69 clinical studies, 73% reported positive outcomes, and the most common bone treated, fracture type, and method of administration were tibia, delayed/non-unions, and PEMF, respectively. Of the 161 survey respondents, most (73%) were aware of the positive outcomes reported in the literature, yet only 32% used EStim in their patients. The most common fracture they treated was delayed/non-unions, and the greatest problems with EStim were high costs and inconsistent results.
Conclusion
Despite their awareness of EStim’s pro-fracture healing effects few orthopedic surgeons use it in their patients. Our review of the literature and survey indicate that this is due to confusion in the literature due to the great variation in methods reported, and the inconsistent results associated with this treatment approach. In spite of this surgeons seem to be open to using this treatment if advancements in the technology were able to provide an easy to use, cost-effective method to deliver EStim in their fracture patients.
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•Recording of auditory units with tetrodes in different regions of a grasshopper brain.•Responses of brain neurons to song models showed poor correlation with behavior.•Electrical ...stimulation was successfully applied at some of the auditory neuropiles.•Stridulation elicited in the deutocerebrum likely activated command neurons directly.•Stridulation elicited in other sites likely activated local brain circuits.
We investigated brain regions – mostly neuropils – that process auditory information relevant for the initiation of response songs of female grasshoppers Chorthippus biguttulus during bidirectional intraspecific acoustic communication. Male-female acoustic duets in the species Ch. biguttulus require the perception of sounds, their recognition as a species- and gender-specific signal and the initiation of commands that activate thoracic pattern generating circuits to drive the sound-producing stridulatory movements of the hind legs. To study sensory-to-motor processing during acoustic communication we used multielectrodes that allowed simultaneous recordings of acoustically stimulated electrical activity from several ascending auditory interneurons or local brain neurons and subsequent electrical stimulation of the recording site. Auditory activity was detected in the lateral protocerebrum (where most of the described ascending auditory interneurons terminate), in the superior medial protocerebrum and in the central complex, that has previously been implicated in the control of sound production. Neural responses to behaviorally attractive sound stimuli showed no or only poor correlation with behavioral responses. Current injections into the lateral protocerebrum, the central complex and the deuto-/tritocerebrum (close to the cerebro-cervical fascicles), but not into the superior medial protocerebrum, elicited species-typical stridulation with high success rate. Latencies and numbers of phrases produced by electrical stimulation were different between these brain regions. Our results indicate three brain regions (likely neuropils) where auditory activity can be detected with two of these regions being potentially involved in song initiation.
Most living organisms possess varying degrees of regenerative capabilities but how these regenerative processes are controlled is still poorly understood. Naturally occurring bioelectric voltages ...(like V
mem
) are thought to be playing instructive role in tissue regeneration, as well as embryonic development. The different distribution of ions on the either side of the cell membrane results in intra- and extra-cellular voltage differences, known as membrane potential or V
mem
. The relationship between V
mem
and cell physiology is conserved in a wide range of cell types and suggests that V
mem
regulation is a fundamental control mechanism for regeneration related processes e.g., proliferation and differentiation. In the present study we measured V
mem
in three different cell types (human osteogenic sarcoma cell line (OSC), rat bone marrow derived mesenchymal stem cells (BM-MSC), and rat dermal fibroblasts) and characterized the relationship between their V
mem
and proliferation. In order to find out if V
mem
controls proliferation, or visa-versa, we blocked and then unblocked Na
+
/K
+
-exchanging ATPase using ouabain and measured the proliferation. Our results demonstrate that V
mem
can be pharmacologically manipulated to control proliferation in certain cell types like BM-MSC. Taken together, it is clear that control of bioelectrical properties in non-excitable cells could prove to be potentially a useful tool in regenerative medicine efforts.
Electrochemical signals play an important role in cell communication and behavior. Electrically charged ions transported across cell membranes maintain an electrochemical imbalance that gives rise to ...bioelectric signaling, called membrane potential or V
. V
plays a key role in numerous inter- and intracellular functions that regulate cell behaviors like proliferation, differentiation and migration, all playing a critical role in embryonic development, healing, and regeneration.
With the goal of analyzing the changes in V
during cell proliferation and differentiation, here we used direct current electrical stimulation (EStim) to promote cell proliferation and differentiation and simultaneously tracked the corresponding changes in V
in adipose derived mesenchymal stem cells (AT-MSC).
We found that EStim caused increased AT-MSC proliferation that corresponded to V
depolarization and increased osteogenic differentiation that corresponded to V
hyperpolarization. Taken together, this shows that V
changes associated with EStim induced cell proliferation and differentiation can be accurately tracked during these important cell functions. Using this tool to monitor V
changes associated with these important cell behaviors we hope to learn more about how these electrochemical cues regulate cell function with the ultimate goal of developing new EStim based treatments capable of controlling healing and regeneration.
•Small grasshopper auditory brain neurons were recorded with multielectrodes.•Signal to noise ratio was higher with 12 μm tungsten compared to 15 μm copper wires.•Stable recordings were achieved for ...30 minutes and more.•Spike sorting and collision analysis discriminated up to 5 units per recording.•Unit identification by comparing extracellular to intracellular data is difficult.
Grasshoppers have been used as a model system to study the neuronal basis of insect acoustic behavior. Auditory neurons have been described from intracellular recordings. The growing interest to study population activity of neurons has been satisfied so far with artificially combining data from different individuals.
We for the first time used multielectrode recordings from a small grasshopper brain. We used three 12μm tungsten wires (combined in a multielectrode) to record from local brain neurons and from a population of auditory neurons entering the brain from the thorax. Spikes of the recorded units were separated by sorting algorithms and spike collision analysis.
The tungsten wires enabled stable recordings with high signal to noise ratio. Due to the tight temporal coupling of auditory activity to the stimulus spike collisions were frequent and collision analysis retrieved 10–15% of additional spikes. Marking the electrode position was possible using a fluorescent dye or electrocoagulation with high current. Physiological identification of units described from intracellular recordings was hard to achieve.
12μm tungsten wires gave a better signal to noise ratio than 15μm copper wires previously used in recordings from bees’ brains. Recording the population activity of auditory neurons in one individual prevents interindividual and trial-to-trial variability which otherwise reduce the validity of the analysis. Double intracellular recordings have quite low success rate and therefore are rarely achieved and their stability is much lower than that of multielectrode recordings which allows sampling of data for 30min or more.
Background Electrochemical signals play an important role in cell communication and behavior. Electrically charged ions transported across cell membranes maintain an electrochemical imbalance that ...gives rise to bioelectric signaling, called membrane potential or V.sub.mem . V.sub.mem plays a key role in numerous inter- and intracellular functions that regulate cell behaviors like proliferation, differentiation and migration, all playing a critical role in embryonic development, healing, and regeneration. Methods With the goal of analyzing the changes in V.sub.mem during cell proliferation and differentiation, here we used direct current electrical stimulation (EStim) to promote cell proliferation and differentiation and simultaneously tracked the corresponding changes in V.sub.mem in adipose derived mesenchymal stem cells (AT-MSC). Results We found that EStim caused increased AT-MSC proliferation that corresponded to V.sub.mem depolarization and increased osteogenic differentiation that corresponded to V.sub.mem hyperpolarization. Taken together, this shows that V.sub.mem changes associated with EStim induced cell proliferation and differentiation can be accurately tracked during these important cell functions. Using this tool to monitor V.sub.mem changes associated with these important cell behaviors we hope to learn more about how these electrochemical cues regulate cell function with the ultimate goal of developing new EStim based treatments capable of controlling healing and regeneration.
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