In one of the biggest discoveries ever made on our endeavor, I and many other height increase seekers and researchers before me found a Patent “Method for non-invasive electrical stimulation of epiphyseal plate growth” (US 4467809 A) and the PubMed research article which was written with the patent “In vivo growth plate stimulation in various Capacitively Coupled Electrical Fields“. In this post, we go back to the patent and the PubMed article to see if we can look deeper into the references and the related articles associated with Dr. Brighton’s work to see whether there is more information we might be able to gain from studying the published works.
I wanted to go to 3 related studies he had published back in the 70s & 80s which all sort of involved the same basic idea. You apply a constant electrical current and put it close to cartilage or chondrocytes and see what will happen as a result.
Study #1: In vitro epiphyseal-plate growth in various constant electrical fields.
- Brighton CT, Cronkey JE, Osterman AL.
- J Bone Joint Surg Am. 1976 Oct;58(7):971-8.
- PMID: 185224
An in vitro epiphyseal-plate model was subjected to various electrical fields. At a voltage gradient of 1500 volts per centimeter, a consistent, highly significant acceleration of growth of the epiphyseal plate occurred as measured from photomacrographs and as indicated by incorporation of 45Ca, 35S, and 3H-thymidine. The growth acceleration was due to voltage gradients and not to current flow. Although the mechanism of action of the electrical field is not known, it is obvious that the voltage gradient, either directly or indirectly, incites a physiological response of the growth-plate chondrocyte.
- J Orthop Res. 1988;6(4):552-8.
- Brighton CT, Townsend PF.
- Source: Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia 19104.
- PMID: 2837556
Abstract
Growth plate chondrocytes from newborn calf costochondral junctions grown in monolayer were subjected to a capacitive AC signal of 500 V peak to peak (P-P) at 60 kHz for 48 h and were analyzed for [3H]thymidine uptake. The stimulated chondrocytes showed a 130% greater uptake over unstimulated controls. Other newborn calf growth plate chondrocytes were stimulated at 500 V P-P at 60 kHz for 2.5, 5.0, 10.0, and 20.0 min and were analyzed for cAMP. Chondrocytes stimulated for 2.5 and 5.0 min showed a 142.8% (p less than 0.05) and 394.5% (p less than 0.01) increase over controls, respectively. The chondrocytes stimulated for 10.0 and 20.0 min showed no significant difference from the controls. It is concluded that short-term exposure of growth plate chondrocytes to an appropriate capacitively coupled field stimulates cAMP production, but longer-term application of the electrical field is ineffective.
- J Orthop Res. 1984;2(1):15-22.
- Brighton CT, Unger AS, Stambough JL.
- PMID: 6491794
Abstract
Isolated articular cartilage chondrocytes from 1- to 3-week-old male Holstein calf knee joints were formed into pellets containing 4 X 10(6) isolated cells and were grown in tissue culture medium (minimum essential medium/NCTC 135) containing either 1 or 10% newborn calf serum (NBCS) in plastic Petri dishes in 5% CO2 and air at 37 degrees C in saturation humidity. On the 4th postisolation day either [35S]sulfate or [3H]thymidine was added to the medium, and the pellets were exposed for 24 h to capacitively coupled electrical fields (10, 100, 250, and 1,000 V peak-to-peak, 60 kHz, sine wave signals). The pellets were then harvested, dialyzed, hydrolyzed, and assayed for DNA, protein, [35S]sulfate incorporation, and [3H]thymidine incorporation. Results indicated that at 250 V peak-to-peak there was a statistically significant increase in [35S]sulfate in 1% NBCS and a statistically significant increase in [3H]thymidine in 10% NBCS. At potentials above or below 250 V no changes were noted. Thus, articular cartilage chondrocytes grown in pellet form can be stimulated to increase glycosaminoglycan synthesis or to increase cell proliferation by an appropriate capacitively coupled electrical field. The importance of the serum concentration in the medium in evaluation of biosynthesis in vitro is noted.
Analysis & Interpretation:
I had already used these studies before in previous posts but they were from many months ago when my knowledge on the subject and the research was still very superficial in nature. This time around I am going to try to go deeper on the details and understand at a deeper level what the implications and applications would be for the results of the studies.
Study #1 is the one that we see has the most interesting of results, at least in the abstract. When we apply a voltage gradient, then the epiphyseal plate cartilage seems to increase in its growth. Since the set up is in vitro, I do wonder just how one tests growth plates in an in vitro setup. Is the growth plate explanted from the test animal?
It is important to note that the growth of the cartilage is from the voltage difference, not from current flow. The optimum gradient they found was 1500 Volts/cm. The term “gradient” refers to differences between two points of some unit in concentration. A Voltage gradient means that if one measured the voltage with two electrodes with one of the electrodes kept in one place, and the other electrodes measured at difference lengths of the growth plate thickness or length, the voltage values relative to the set point would be changing. The growth plate’s increased growth is found through testing using Calcium, Sulfur, and Thymidine, and a type of imaging technique known as photomacrographs. The actual mechanism of how the applied electrical field actually works to increase growth plate increased growth is not known but the conclusion made by Brighton is that the voltage gradient created when the electrical field is generated is what will directly o indirect stimulate the chondrocytes.
In Study #2 we see that instead a DC current created a steady state electrical signal, Brighton tried to use an AC signal instead to see what would happen. The researchers took growth plate cartilage from a newborn calf’s ribcage area and put the chondrocytes in a monolayer structure. The AC electrical signal is induced at 500 Volts for the amplitude and the frequency being 60 Hz. The field is applied for 2 days (48 hours) and the chondrocyte concentration was tested by using thymidine uptake. There was a 130% increase over unstimulated chondrocyte controls. So the researchers tried the AC electrical field stimulation to test to see whether the chondrocytes would show increased cAMP production. When the 500 Volt amplitude, 60 Hz signal was applied, the 10 min & 20 min duration showed to increased cAMP production increase, but the 5 min and 2 min did show increased cAMP increase. This shows like so many other stimulants, if we want to make the chondrocytes in growth plates increase in cAMP production, which is one of the things we will need to do to make chondrocytes go faster, we have to have a optimum duration time for electrical signal stimulation. The optimum seems to be just a short term, 5 min. round which would increase the cAMP production by over 4 times.
In study #3 brighton ans other researcher took chondrocytes from newborn calf knee joints. The chondrocytes were put in pellets with the concentration of chondrocytes around 4,000,000 in each pellet. The pellets were grown in a tissue culture medium with different concentrations of calf serum in petri dishes. In 4 days after the chondrocytes were separated from the calf, the thymidine and/or the sulfate was injected into the culture. Then the capacitative electrical field was applied. The variable that was changed was the amplitude of the sinusoidal signals, which ranged from 10 volts to 1000 volts. The frequency was 10 kHz and the duration was 24 hours. Afterwards the pellets were taken, and treated to test to see how much DNA, proteins, sulfate uptake, and thymidine uptake the chondrocytes had done. With the 1% newborn calf serum in the culture, the 250 Volts led to a high sulfate uptake by the chondrocytes while the 10% newborn calf serum in the culture had the 250 volts cause a very high uptake of the thymidine. The researchers conclude with…
Thus, articular cartilage chondrocytes grown in pellet form can be stimulated to increase glycosaminoglycan synthesis or to increase cell proliferation by an appropriate capacitively coupled electrical field.
The implications and main things we should take away from the studies we just took at is the idea that we can easily create a device that can produce either the DC or AC electrical signals we need at the high voltage amplitudes and the frequencies we need to stimulate either the articular cartilage chondrocytes or the epiphyseal growth plate chondrocytes. If we can get any type of mesenchyme in the bone to differentiate into chondrocytes, the application of the right duration and voltage gradient of capacitative electrical signal would mean that the chondrocytes might start proliferating, which could result in even adults with no growth plate cartilage to develop cartilage again.