Author Archives: Tyler

LSJL studies 5: LSJL device design

This paper discusses a lateral bone loading device.  It mentions a capacity of 40N which I think won’t be enough for lengthening purposes as since lengthening post growth plate senesence is an abnormal task it probably requires very abnormal stimuli.  It’s interesting to look at the device though.

The study mainly mentioned the technical design of the device and no analysis of the applications.

A Mechatronic Loading Device to Stimulate Bone Growth via a Human Knee

“This paper presents the design of an innovative device that applies dynamic mechanical load to human knee joints. Dynamic loading is employed by applying cyclic and periodic force on a target area. The repeated force loading was considered to be an effective modality for repair and rehabilitation of long bones that are subject to ailments like fractures, osteoporosis, osteoarthritis, etc. The proposed device design builds on the knowledge gained in previous animal and mechanical studies. It employs a modified slider-crank linkage mechanism actuated by a brushless Direct Current (DC) motor and provides uniform and cyclic force.”

Here’s an example of what slider crank linkage looks like:

slider-crank-linkage

“The functionality of the device was simulated in a software environment and the structural integrity was analyzed using a finite element method for the prototype construction. The device is controlled by a microcontroller that is programmed to provide the desired loading force at a predetermined frequency and for a specific duration. The device was successfully tested in various experiments for its usability and full functionality. The results reveal that the device works according to the requirements of force magnitude and operational frequency. This device is considered ready to be used for a clinical study to examine whether controlled knee-loading could be an effective regimen for treating the stated bone-related ailments{Hopefully bone length is one of those bone-related ailments unfortunately Ping Zhang’s name is not on this paper and he was always the one more interested in bone length}.”

“When a specific loading force is applied to the epiphyses of the femur and tibia, the trabecular bone tissue, which is characterized by axial stress resistance, resists this force from the opposite direction. This results in deformations in that area. These deformations create a variation of the fluid pressure in the intramedullary cavity. This pressure gradient allows the flow of fluids that carry essential nutrients to the bone cortex initiating osteoblast differentiation and osteogenesis, thus helping in repair and regeneration of the bone tissue. This unique reaction makes this procedure an effective treatment for bone rehabilitation. It helps in reduction of healing time of bone fractures and hastens recovery from bone-related injuries and diseases. The lateral stress application is also less strenuous to the knee bone and reduces the amount of force that needs to be applied to get this result.”

pressure-caused-by-fluid-flow

B is the force we’re looking for.  The pressure generated by fluid flow not just on the bone but on the stem cells to initiate chondrogenic differentiation.  The pressure on the intact bone may also allow the creation of cartilage canals to enable that requirement for a neo growth plate.

It’s also interesting to note that in the proposed knee loading device the load the entire lateral area of the epiphysis this may be a way to reduce slippage.

” it was decided that the proposed device should be robust enough to produce different magnitudes of linear force up to a maximum of 40 N”<-Since lengthening is not being considered in this study forces required for lengthening may be higher.

lsjl-dev-ice

The device doesn’t look wide enough for the knee really.  The dimensions of the device listed are:

Length: 0.3 m
Width: 0.1
Height: 0.2

There are about 39 inches in a meter so about 3.9 inches in width.  I don’t know if that’s enough.

Also the device looks more like this kind of clamp:

Then the other clamps we’ve been using.    Although you’d have to make new pads to actually adjust to knee.  Well actually more like:

But the pipe gets in the way of getting around the knee.  Although I’m not really sure that a pipe clamp is superior to the other clamps.  I’m just pointing out that it’s the clamp that looks most like the design mentioned in the study.

Here’s some more details on the device:

sensors-16-01615-g004

Here’s an actual physical prototype:

more-advanced-protoype

LSJL Update 9-27-2016

Here’s the last LSJL update.  Here’s the feet images from the this time which have had the best results out of what I’ve been clamping:

20160927_083012

The size increase is not due to flattening of the arches as the arch on the right foot actually looks bigger.  You’ll note that the second and third toe look bigger as well.  My wingpsan has increased from 74.5″ to 74.75″ up from the 72.5″ it was before I started LSJL.  It is very difficult however to take a good wingspan picture.

Part of the trouble with LSJL has been slipping when clamping and a possible solution is that rather than clamping the epiphysis of the bone is to clamp the neck of the bone.

20160927_161437

Considering the spillover of the second and third toe growth, I’d say it’s probably more important to generate clamping force than it is to be at the optimal location.  Clamping at the neck of the bone also clamps the muscle as well which result in more fluid flowing into the bone.  Also clamping at the neck of the bone gets closer to the bone marrow and one key conclusion I’ve come to my LSJL research so far is that the cortical bone and the outer periosteum(growth in width is difficult as well as growth in length) inhibit bone growth and inner periosteum and bone marrow stimulate bone growth.  Distraction osteogenesis both gets rid of cortical bone via fracture and stimulates the bone marrow via blood clot.

By continuing to clamp the epiphysis of the bone is likely the reason why my length gains plateaued as whenever I tried to increase the clamping force the clamp would slip off.  By clamping the neck of the bone I can continue to increase the clamping force without having to worry about slippage.  Hopefully, this will allow me to get some leg length increases that I’ll be able to report otherwise I’ll see if I can continue to gain in the feet and that’ll be proof of concept that I can use to gain more resources to establish better clamping technology to gain in the legs.

I bought a new clamp for my fingers as the standard six inch clamp was just too big.

The problem with this is all the holes in the clamp that make clamping uncomfortable.  If neck clamping with the Irwin Quick Grip clamp doesn’t work

 

I can doing the C-class clamp again but I worry even with clamping the neck of the bone rather than the epiphysis there’ll be too much slipping.

We’ll see what happens in one to two weeks.  And if it doesn’t seem to be working I’ll switch it up.  Considering my foot growth if I don’t observe results in a reasonable time frame then it’s time to switch things up

 

LSJL Update 9-13-2016

I tried hand clamping but I seemed to plateau with it so I’m back to using the C-class but more intensely than before.  Here is me doing some bones with a C-class clamp.  I’ve been getting some progress with my feet at least but that could be because changes in the feet are more noticeable because my shoes feel more snug.  Here’s the last feet images I took for comparison.  The first image there is actually the before picture.  Also the II phalanxes(toe closest to big toe) seems longer as well which makes sense since I’m clamping close by.

But my feet seemed to go up in size very quickly once I change methodology of using the C-class clamp over the hand clamp.  So if there’s no changes in a week then I will try something different.  Michael thought about using two C-class clamps at once.  Ideally, yes you want to gain height but the feet is where I’m getting results and if my right shoe no longer fits that would be hard to deny proof and I could use that proof to acquire more resources to translate to height increase research.

Since the II toe is growing I’m worried less about a precise clamping location and more about clamping force.  Now it is possible that the feet could be flattening but the big toe is already pretty straight.  Well if I can keep getting results than such minutiae won’t matter.

Here’s pictures of my feet:

20160913_172028

The right toe is bigger.  I’m not to the point where I need to go up a size for my right foot but I’m closer.

Here’s some unilaterally swollen feet:  The bones don’t physically look longer.  So I don’t think it’s swelling making my feet appear longer.

one-swollen-foot

Here’s another unilaterally swollen foot:

ryans-swollen-feet

Here’s another:

another-unilaterally-swollen-foot

Myxedema

Myxedema increases hydrostatic pressure by resulting in increased deposition of connective tissue elements like hyaluronic acid and GAGS(chondroitin).  Maybe there’s a way to use the pathology of this disease to safely increase the deposition of connective tissue to possibly increase height.

Increases in deposition of this elements can result from scar tissue.  Perhaps the separation in limb lengthening surgery can be thought of as a form of scar.  Increases in Fibroblast levels also could increase accumulation of connective tissue.  It is worth it to note that FGFR3 decreases height.  Maybe an interesting possibility is that FGFR3 reduces circulation Fibroblast levels and decreases hydrostatic pressure and results in a height increase that way. Thyroid hormone is thought to increase these connective tissue elements.

Maybe in pregnancy the elevated thyroid causes the bump in the stomach during pregnancy and possibly causes the increase in shoe size and height.  Being pregnant can increase the size and production of the thyroid.

Actors like Feldman who had graves disease was not tall at 5’7″.

Other famous with Graves:

Missy Elliott-F 5’2″

Rodney Dangerfield-M 5’10”

1st President Bush-M 6’2″

Maggie Smith-F 5’5″

According to this paper Graves’ disease–acceleration of linear growth., Grave’s may cause an acceleration of linear growth but I could not find anymore beyond the title.

Body height and weight of patients with childhood onset and adult onset thyrotoxicosis.<-Thyrotoxisis is another name for hyperthyroidism

“The present study has compared body height and weight of thyrotoxic female patients of childhood onset and adult onset. The body height of 141 out of 143 (99%) adult-onset thyrotoxic patients was within the range of mean +/- 2SD for the age-matched general Japanese female population. On the other hand, in 42 patients with childhood-onset thyrotoxicosis, 6 (14%) had their height being greater than the mean + 2SD of general population, and 34 (81%) were taller than the mean value. In 86 patients with siblings, 42 (49%) were at least 2 cm taller than their sisters, and 26 (30%) were more than 2 cm shorter than their sisters. The body weight of 27 out of 42 (68%) patients younger than 20 years was not decreased but was even greater than the mean value for the age-matched general population. The results indicate that excessive thyroid hormone in vivo enhances body height in humans. The increased body weight in some young patients suggests that enhanced dietary intake due to increased appetite in hyperthyroidism has overcome the energy loss with increased metabolism.”

If you look at figure 1 you get quite a interesting figure that shows that of females with adult onset hyperthyroidism tend to be taller than the mean(this is not a longitudinal study so hyperthyroidism could not be a direct measurement of height increase).  I could not excise the figure out of the study you will have to look at it directly.

46, XY pure gonadal dysgenesis: a case with Graves’ disease and exceptionally tall stature.

“Growth was arrested with height remaining at 187 cm after normalization of the thyroid function by treatment with an antithyroid agent, although follow-up to monitor growth was limited to 3 months. In some cases of gonadal dysgenesis, then, Graves’ disease may contribute to an abnormally tall stature.”

So we see that Grave’s disease has an impact on height but that the affect on height is variable sometimes an increase and sometimes a decrease.  Maybe there’s some other variable like FGFR3 levels that influence the effects on height.

This provides more evidence that hydrostatic pressure influences height but perhaps some other stimuli is needed like CNP as increases Fibroblastic stimuli would result in more FGFR3 stimuli in some cases.  CNP would cancel that out.

Could an MMP supplement help you grow taller?

Some supplements affect MMP expression.  Zinc suppresses MMP2 and MMP9(Zinc Regulates Lipid Metabolism and MMPs Expression in Lipid Disturbance Rabbits.) and Selenium decreases MMP2 and TIMP1 levels(Selenium’s effects on MMP-2 and TIMP-1 secretion by human trabecular meshwork cells).

Effects of matrix metalloproteinases on the fate of mesenchymal stem cells.

“Mesenchymal stem cells (MSCs) have great potential as a source of cells for cell-based therapy because of their ability for self-renewal and differentiation into functional cells. Moreover, matrix metalloproteinases (MMPs) have a critical role in the differentiation of MSCs into different lineages. MSCs also interact with exogenous MMPs at their surface, and regulate the pericellular localization of MMP activities{so you could supplement with exogenous(external from the body) MMPs to manipulate MSC and hopefully induce chondrogesis}. The fate of MSCs is regulated by specific MMPs associated with a key cell lineage. Recent reports suggest the integration of MMPs in the differentiation, angiogenesis, proliferation, and migration of MSCs{all these four things are likely factors related to chondroinduction}. These interactions are not fully understood and warrant further investigation, especially for their application as therapeutic tools to treat different diseases. Therefore, overexpression of a single MMP or tissue-specific inhibitor of metalloproteinase in MSCs may promote transdifferentiation into a specific cell lineage{this could help you grow taller if it’s transdifferentiation towards a chondrogenic lineage the official term for neo growth plate formation would be something like interosseous chondrofication}, which can be used for the treatment of some diseases. In this review, we critically discuss the identification of various MMPs and the signaling pathways that affect the differentiation, migration, angiogenesis, and proliferation of MSCs.”

“Collagenases (MMP-1, MMP-8, MMP-13, and MMP-18) cleave fibrillar collagen types I, II, and III, and they can cleave other ECM proteins. Gelatinases (MMP-2 and MMP-9) have high activity against gelatin, and degrade other ECM molecules including collagens, laminin, and aggrecan. Stromelysins (MMP-3, MMP-10, and MMP-11) digest a number of noncollagen ECM molecules, and their domain arrangement is similar to that of collagenases. The membrane-type MMPs (MT-MMPs) (MMP-14, MMP-15, MMP-16, MMP-17, MMP-24, and MMP-25) are intracellularly activated transmembrane molecules, and their active forms are expressed on the cell surface. There are other less characterized members including MMP-7, MMP-12, MMP-19, MMP-20, MMP-22, and MMP-23”

“MMPs have critical role in the differentiation of MSCs to adipocytes, osteocytes, and chondrocytes. MSCs interact with exogenous MMPs at their surface and activate proMMP-2 and proMMP-13, regulating the pericellular localization of MMP activities. They have the capability to regulate exogenous MMP-2 and MMP-9 by the expression of TIMP-2 and TIMP-1, protecting the perivascular niche from their high levels”

“silencing of MMP-2 by siRNA impaired chondrogenic differentiation, and increased the protein level of fibronectin and β1 integrin. Treatment with a MMP-2 activator resulted in the activation of chondrogenesis.

“MMP-2 is involved in the chondrogenic differentiation of MSCs via downregulation of focal adhesion kinase (FAK)–β1 integrin interaction, which leads to phosphorylation of FAK”

“the degradation of MMPs enhances the chondrogenic differentiation of MSCs by allowing the morphological changes and increasing the contents of glycosaminoglycans (GAG) and expression of chondrogenic markers. A chondrogenic cell line (ATDC5) was examined for chondrogenic differentiation, and the expression of MMP-2, MMP-9, and MT1-MMP was upregulated during the early stages of chondrogenic differentiation with a downregulation in the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK)”

“t the increase in production of MMP-13 drives the MSC differentiation to chondrocytes by degrading the cleavable components of the ECM, and regulating integrin-binding peptides”

“Stimulation of MSCs in chondrogenic media with IL-β1 resulted in increased expression of MMP-2, MMP-3, and MMP-13 while IL-6 downregulated the expression of MMP-3 and MMP-13 compared with control without stimulation”

” Commitment of MSCs to differentiate into a specific lineage, proliferate, or migrate is regulated by many factors in the local tissue microenvironment.”<-So finding a way to stimulate MMP2 on it’s own may not be enough on it’s own to create chondroinduction.

mmp-differentiation-regulation

Hydrostatic skeleton: Key studying point for height growth

One way to develop new height growth techniques would be to study how the hydrostatic skeleton works and since hydrostatic pressure is a key way that hydrostatic skeletons stay structurally sound.  We can use the methods that hydrostatic organisms generate hydrostatic pressure and use those methods on our endoskeletons.

“A hydrostatic skeleton or hydroskeleton is a structure found in many soft-bodied animals consisting of a fluid-filled cavity, the coelom, surrounded by muscles.”

Here’s an image:

hydrostatic skeleton

Another description: ”

A hydrostatic skeleton is one formed by a fluid-filled compartment within the body: the coelom. The organs of the coelom are supported by the aqueous fluid, which also resists external compression. This compartment is under hydrostatic pressure because of the fluid and supports the other organs of the organism. This type of skeletal system is found in soft-bodied animals such as sea anemones, earthworms, Cnidaria, and other invertebrates .”

“earthworms move by waves of muscular contractions (peristalsis) of the skeletal muscle of the body wall hydrostatic skeleton, which alternately shorten and lengthen the body”<-earthworms grow shorter and taller almost at will.

Another description:

“A hydrostatic skeleton is a structure found in many cold-blooded and soft-bodied organisms. It consists of a fluid-filled cavity, which is surrounded by muscles. The cavity is called a coelom and in some animals this cavity is filled with a blood-like substance called haemocoel. The fluid presses against the muscles, which in turn contract against the pressure of the fluid. The fluid is incompressible and thus maintains a constant volume against which the muscles can contract.”

Maybe high hydrostatic pressure in bone serves as a temporary hydroskeleton which allows for temporary loss of osteo-structural components and allow for things such as the growth plate.  Maybe we need to stop think of it is an osteochodral skeleton but a hydroosteochondral skeleton where the hydroskeleton allows the skeleton to function without all the osteocomponents.

ONTOGENETIC SCALING OF HYDROSTATIC SKELETONS: GEOMETRIC, STATIC STRESS AND DYNAMIC STRESS SCALING OF THE EARTHWORM LUMBRICUS
TERRESTRIS

“Hydrostats are constructed of an extensible body wall in tension surrounding a fluid or
deformable tissue under compression. It is the pressurized internal fluid (rather than the rigid levers of vertebrates and arthropods) that enables the maintenance of posture,
antagonism of muscles and transfer of muscle forces to the environment”

“The major source of static load on the body wall of a hydrostatic skeleton is internal pressure (P). Pressure can be generated by the contraction of muscles in the body wall surrounding the incompressible fluid and/or by mechanisms such as ciliary pumps (e.g. in sea anemones), osmotic pressure (e.g. notochords) and gravitational pressure (the gradient of pressure
produced in a static fluid by its own weight”

“hydrostats tend to be highly deformable”

“The main source of loading on the skeleton of most terrestrial organisms with rigid skeletons is body weight. In earthworms, the main source of loading on the skeleton is internal pressure (generated by body wall muscles contracting against a constant volume of internal fluid)”

“The upper limit to the size of hydrostatic skeletons is unclear, but some of the possible limitations to giant earthworms include (1) a decreased respiratory surface area
due to the low surface-to-volume ratio compared with that of smaller earthworms, (2) an increased importance of gravitational pressure as a source of load on the body wall, (3)
an increased frictional resistance to burrowing, and (4) the exponential increase in the cost of tunnel construction with increasing body diameter”<-An upper limit to hydrostatic skeletons would not be good as it would imply limitations on generation hydrostatic pressure but none of these reasons would seem to impede a structural limitation on hydrostatic skeleton size.

Scaling of the hydrostatic skeleton in the earthworm Lumbricus terrestris.

“We used glycol methacrylate histology and microscopy to examine the scaling of mechanically important morphological features of the earthworm Lumbricus terrestris over an ontogenetic size range from 0.03 to 12.89 g. We found that L. terrestris becomes disproportionately longer and thinner as it grows. This increase in the length to diameter ratio with size means that, when normalized for mass, adult worms gain ~117% mechanical advantage during radial expansion, compared with hatchling worms. We also found that the cross-sectional area of the longitudinal musculature scales as body mass to the ~0.6 power across segments, which is significantly lower than the 0.66 power predicted by isometry. The cross-sectional area of the circular musculature, however, scales as body mass to the ~0.8 power across segments, which is significantly higher than predicted by isometry. By modeling the interaction of muscle cross-sectional area and mechanical advantage, we calculate that the force output generated during both circular and longitudinal muscle contraction scales near isometry.”