I do read the comments people leave on the website. Most of those, I don’t respond back, because the person would not put any effort in asking a real question that was worth even thinking about. Only rarely does someone actually write something which is even long enough and technical enough for me to take notice. If you want to get an answer or a response, put some time and real effort in leaving a message. Asking me for a free E-book or a program doesn’t do it.

(Picture Source)

Something that the regular readers have said was the desire on an update on the breakthrough chemical which I mentioned in the post “The Chemical That Would Make Adults Grow Taller Has Been Found – Game Changing Post!“. The claim is that I don’t seem to ever dig deep enough on certain ideas that I share. Well, I will give you the reader an update. I have my personal life and professional life to deal with. This website and project has always been a work of love.

For some background, in that post before I had theorized that this chemical known as Relaxin is the most interesting chemical to ever be found by me or Tyler, and it does have height increasing effects for adults with ossified physis cartilage. How is that even possible? It doesn’t regrow a new growth plate,  but can cause the ligaments and muscles in the area to increase in flexibility. Just like how going to a chiropractor might lead to one having the back readjusted and leading to a height increase for a short time, the lengthening of ligaments in the joint areas of the body will also lead to some level of body lengthening. Not only that, there are receptors in the chondrocyte in growth plates and bone tissue. which respond to the relaxin protein.

In that previous post, I had said that a Dennis Stewart from Bas Medical had been willing to spend around $5,000 to file a patent for this idea, of using Relaxin to remodel bone sutures and in that Patent (refer back to that post) it was claimed that a local injection of relaxin to the growth plate-bone area would result in as much as 30 cm of bone length increase (12 inches).

I am quite certain that over 50,000 readers have already seen that post. Some have gone ahead and looked further into this chemical, to find out what they could from it. One commenter said that relaxin is something humans should avoid taking due to the possibilities of “gynecomastia, hyperestrogenism and most likely CANCER”. Others have shown that it would be very hard, if not impossible to get this compound.

For the claim that this compound is possibly carcinogenic, that is a definite possibility. When I was doing research on PTHrP, the chemical was also shown to allow single cells to proliferate at a high rate which would be considered carcinogenic. However, that is the problem with this type of research. Any compound that can extend the natural limit of cell life or cell proliferation is doing the exact same thing as cancer cells. We are in essence trying to push past the natural growth phase of the human organism. That is why it is highly likely that the chemicals which we claim can increase the limit of chondrocyte proliferation would also have cancer-stimulating effects. Any form of cure or vaccine in large doses will turn poisonous and harmful. They are the exact same thing, just different sides of the same coin.

So here is what I was able to find out, although I have not been putting too much effort into it.

Refer to the Patents below (Note: a Samuel Yue was the patent inventor of 2 of the 3 patents)…

1. By administering relaxin and glucosamine sulfate to treat osteodegenerative dysfunction in a patient with joint and hip pain; administering relaxin and estrogen to treat alzheimer’s (Patent # US 6251863 B1)
2. METHOD OF TREATING INVOLUNTARY MUSCLE DYSFUNCTION WITH RELAXIN HORMONE (Yue, U.S. Pat. No. 5,612,051)
3. Spinal stabilization treatment methods for maintaining axial spine height and sagital plane spine balance (Patent # US 20090093852 A1)

From the 1st patent…

“…Relaxin’s effect on connective tissues during late pregnancy has been well-documented. Relaxin improves the integrity of the connective tissues, maintains the elasticity and circulation of the skin, sustains the youthful and radiant appearance of the face, increases hair and nail growth, and stimulates other changes during pregnancy….Fibromyalgia patients who receive relaxin supplements report a significant decrease of muscle tightness, increased range of motion in their joints, and decreased stiffness of the ligaments and tendons surrounding the joints….relaxin supplements will be given to these individuals who suffer congenitally (probably secondary to borderline deficit of relaxin) from tight muscles, ligaments and tendons to restore the flexibility of the joints and eliminate or arrest the osteodegenerative disease of the joints”

“…Therefore, the production of the collagen by the chondrocytes is facilitated by relaxin. Good quality collagen is produced in the presence of relaxin, which binds with proteogylcan to form strong resilient cartilage. Together with the deactivation of the collagenase by the glucosamine sulfate, homeostasis of the cartilage regeneration and degeneration are maintained and the joint is returned to its formal healthy state. Accordingly, relaxin enhances the effect of glucosamine sulfate in retarding and restoring osteodegenerative changes of the joints.”

I once claimed that almost any type of chemical that an help with treating the pain associated with osteoarthritis or cartilage degeneration has a potential height increasing effect to it as well, after doing research on the effects of Harpagoside on arthritis. It is also known as Devil’s Claw.

It seems that this first patent shows that when you combine Relaxin with Glucosamine Sulphate together, the effect on people suffering from both Osteo-degenerative disease and Fibromyalgia is quite large and profound.

For the regular readers, I am sure that they are fully aware that besides Relaxin, Glucosamine Sulphate was probably the other chemical that was the best option for people interested in growing taller. Glucosamine Sulphate and Relaxin have been the two compounds which was discovered with the highest level of success for adult height increase, even though the affect may more often be just decreased pain in the joint.

In a later section, the patent also shows that Relaxin can be used to stop the onset of osteoporosis, revealing that it is also a bone mineral density stimulant. So it has two effects 1) Combines with Glucosamine Sulphate to treat osteoarthritis and 2) Helps treat Osteoporosis.

From the 3rd Patent

This patent itself was an idea on how to restore the height lost from a compression on the vertebrate bones. The section of the patent where it mentions the use of relaxin in this height increasing invention/technique is where it mentions the different types of muscle relaxers which can be used.

“Other important considerations in the procedure are the state of the patient’s spine at the time of the procedure. For example, if the procedure is performed in the morning, as opposed to latter in the day, the patient may end up with a different height, as disc height is greatest in the morning after a night of sleep due to increased fluid intake, and decreases with axial loading throughout the day. As such, in some embodiments at least the disc treatment portions of the procedure may be performed in the morning shortly after awakening to facilitate increased height of disc fill, for example. This aspect is further refined by the addition of pre-procedure muscle relaxation with intravenous or intramuscular injection of approved pharmaceuticals, e.g., robaxin, skelaxin, soma, etc. In other embodiments, use of paralyzing agents with general anesthesia may be used for more rigid or stiff patients. Use of SSEP (Somatosensory evoked potential) monitoring may be employed to protect the patient against over distraction or correction, elongation or shortening of the spine resulting in spinal cord injury or other nerve injury.”

“To this end, traction, bracing, suspension, inversion tables, therapy, muscle relaxants, chiropractic adjustments, etc. may be used to advantageously place the spine in the desired position prior to the procedure, at Block 112. Moreover, medication such as ligament relaxors (e.g., relaxin) may also be used to achieve natural elongation of the spine before the procedures, and after as well, to achieve the desired axial height increase/stability.

Various combinations of traction, stretching, operating room or office machines, tables, and other equipment may be used. In some embodiments it may be beneficial for patients to have manipulation manually of the spine before procedures to increase height of the disc, hydrate the disc, as well as enzymatically or surgically remove parts of a damaged disc or other anatomical components (e.g., bone) in preparation for the procedure.”

It seems that the person who wrote up this patent fully realized that relaxin, as a type of ligament relaxor, can be used to naturally elongate the spine.

Later in the patent, I quote this section below….

“In another example, a 45-year-old man, who is 5 feet 4 and has always desired greater height, asks his doctor if there is any way to “safely” be taller. The patient would enter index determination, pre-procedure stretching, traction medical muscle and/or ligament relaxor treatment, etc. After a desired elongation (e.g., 1-2 inches) through this pre-treatment, an early morning procedure may be performed to stabilize the appropriate anatomic structures, namely disc and facet joints, and interspinous ligaments (but not vertebral bodies) to maintain this increased height gain. If at some later point in his life it is determined that he is at risk for fractures, then the vertebral bodies could be subsequently stabilized.”

This patent almost states in very simple, elementary school level terms that a 45 year old man can use Relaxin in a program to increase his height by 1-2 inches, combined with stretching, traction, and the actual surgical treatment. Sure, there is always the surgical part, but with a slight implant, you would end up maybe 1.5 inches taller after just 3 days of hospital stay. Much, much faster than any type of limb lengthening surgery today.

Another idea on how to decompress the height of the discs I refer to in the following… “If a patient has spinal stenosis, then the vertebral bodies would be turned into magnets and then manipulated into distraction to stretch the disc, neuroforamina and hence indirectly decompress the nerves.”

From the 2nd patent….

“…Relaxin is well known as an agent for remodelling the reproductive tract via collagen remodelling before parturition, thereby facilitating the birth process….Relaxin is known to increase in peripheral plasma 7-10 days after the midcycle surge of luteinizing hormone and continues to rise to over 800 pg/ml by three weeks if conception occurred. During pregnancy, relaxin levels peak at the 10th week and are maintained at about 500 pg/ml for the remainder of the pregnancy…During pregnancy, relaxin remodels the reproductive tract which includes ripening of the cervix, thickening of the endometrium of the uterus, increasing vascularization of the uterus, and affecting collagen synthesis to cause ligaments and connective tissue to elongate and relax.”

“The relaxin hormone will alleviate these conditions since relaxin acts to effect collagen formation and collagen remodelling. Relaxin will alleviate the generalized pain and tenderness by elongating muscles and accentuating joint laxity by remodelling connective tissue (e.g ligaments, tendons, bone, etc.) via collagen changes. This expected effect is based on many studies that have observed that pregnant women have elongated pelvic area muscles, and increased joint laxity resulting from the remodelling effect induced by relaxin“

Note two very important things that this inventor Samuel K. Yue has stated.

1. Relaxin causes connective tissue to elongate and relax
2. Relaxin elongates muscles and joint laxity by remodelling connective tissue like bones through collagen changes.

Do we not remember one of the first few things we ever learned about cartilage and bone tissue?

1. Cartilage is made from collagen type II, 
2. Bone is made from hydroxyapatite calcium crystals which give it compressive strength and then collagen (Maybe type I and type III) which gives it tensile strength. 

If the effect of relaxin is mainly on causing collagen changes, then it changed the tensile strength of the bones which have relaxin receptors. One may not have any more growth plate cartilage to elongate, but if the collagen in the bones are temporarily being decomposed by a relaxin-collagenase type effect, then the tensile strength of bones may be dramatically reduced for a short time during pregnancy.

Even today, I got another message to the website from some woman who says that she grew 1 inch from pregnancy.

This Lauren women who seems to be an alumni from Baylor writes the following in the clipped picture above.

“A few months into my pregnancy I noticed that my sister and mother didn’t seem quite as tall. I Told them I think I am growing and they agreed. I am 8 mo pregnant and measuring almost 1″ taller than the 5′ 5″ I started out at. I’m 27yrs old and didn’t really expect to grow anymore, but I’m not complaining.”

Of course, we are talking about bones here, which have a really high strength. If might be that instead of the relaxin causing the tensile strength of bone to temporarily drop, some other connective joint area of the body was loosened. That would make more sense because evolutionarily speaking, it doesn’t make sense to make a pregnant females pelvis and femur weaker while at the same time having the unborn baby hanging down on the stomach. The pregnant women, being bipedal, when standing up would collapse with weak leg bones.

Of course, then we have to add in the fact that during pregnancy, the level of calcium in the pregnant mother drops too.

Maybe the combined effect of both the calcium being transferred from the mother to the baby and then the effect of relaxin changing the level of collagen in the bones means that the bones just might be weak enough (with both a compressive and tensile strength decrease) that lying down in bed for most of the time and eating a lot of ice cream means that the female body can have the bones weak enough for a slight bit of elongation.

I refer the reader to this website of a Trinity Mills Chiropractor Clinic (website here). They write the following…

“Pregnant women commonly are more flexible due to the hormone relaxin that the body produces to make the pelvis more flexible in preparation for childbirth.  Although these are relatively harmless causes, hypermobility can also be an indication of more serious underlying diseases.  Marfan’s syndrome and Ehlers-Danlos syndrome are associated with hypermobility.  Hypermobility can also contribute to the development of osteoarthritis”

For the regular readers, they might remember that I wrote posts about Ehler’s Danlos syndrome before, and that was because certain females who suffer from Ehler’s Danlos syndrome in their later adult years noticed height increase as well. As for Marfan’s Syndrome, that is also associated with tall stature, due to the connective tissue becoming more elongated. It seems that relaxin has the same type of physiological effect as Ehler’s Danlos and Marfans. It causes the connective tissue to stretch out, and in doing so, the overall person’s body ends up taller.

So does this mean that the chemical relaxin has a chance of making adults with closed growth plates end up taller?

Yes, and that is only said with maybe a 65% confidence level. This research I am doing, it is amateur level at best, since I don’t have a team with me, and I have to collect anecdotal evidence from around the internet. There has been over 20 females who have come forth that I have found which claim that their height changed due to pregnancy. All the physiological steps which would allow for such a thing points to relaxin’s handy work. There is a chance to get the same effect, we also need to have a calcium transfer as well to weaken the bones (ie female pregnancy).

This compound has a synergistic effect combined with Glucosamine Sulphate for symptoms of osteoarthritis, and it has been referenced in patents which were created for a height increasing technique, although surgical in nature. The patent filer explicitly states that you can elongate the spine using this chemical. It has connective tissue remodeling abilities, and I would suspect from the Patent by Dennis Stewart that it is on both cartilage and bone types.

Some people do claim otherwise, like the poster who said “if this method would really work – some people would already made business out of it, and selling the product and injecting it in people for increasing hight.”

That is always the first thing a person who doesn’t believe that a new technique is theoretically possible would say. However, do they realize just how much money and time it takes to bring a new medical technique or drug into the market these days? It costs around $500 Mil just to bring a drug which can lower our cholesterol into the market. Even if we showed all the technical theory was accurate and viable, it would still take over $1 Bil to bring this technique to the mass market, which would be years in the making. It is a huge gamble for the large companies.

Plus, they don’t realize just how difficult it is to get this compound. It is extraordinarily expense. The pregnant female will obviously get it for free though. In addition, the actual effects of using it will vary greatly. For just 1mg of this compound, it would cost a person maybe $100,000 and that doesn’t guarantee that it is enough to have any type of big effect on the collagen level of the bones.  I do want to thank some commenter who showed that Novartis bought the rights to make a synthetic version of Relaxin Type 2, known as Serelaxin, RLX030. We as non-medical professionals or chemical lab researchers won’t be allowed to legally get this drug. However, I am sure that with enough money, can get some lab in India or China to make it.

Like most people these days, I do waste a high percentage of my time just browsing Youtube for interesting videos. One Youtube profiler who caught my eye recently is this Canadian female who most people would consider attractive, based on Western/American/European standards. long blue hair, light blue eyes, relatively non-obese, sweet tempered, with a good sense of humor. She doesn’t seem like the most intelligent person in the world you would meet, with the ability to solve complex partial differential equations, but that is besides the point for this post.

Her boyfriend, from the country of Switzerland, seemed like a relatively nice person as well. The most defining trait about him was that he is abnormally tall, which I guess to be 6′ 8″ with a slightly above average face but a good demeanor.

While it may be enough for some heterosexual male to just be looking at an attractive female (the reward-dopamine neuro-pathway in the brain is triggered over and over again), me being a researcher started to go back to this old hypothesis on the idea that there is a correlation between the attractiveness of a females and the height of her chosen male romantic partner.

I would come across the study “Height predicts jealousy differently for men and women” which showed that based on the height of males, there was an inverse relationship between height and level of jealousy. For females, the results showed that for females of average height, they felt more jealousy when meeting someone who possesses qualities which they didn’t have.

One study that they did reference was “Feingold, A. (1982). Do taller men have prettier girlfriends? Psychological Reports, 50, 810.” The abstract showed that when looking at only a 72 male subject group, male groups that were around 2.6 inch shorter had less attractive female romantic partners, on average, based on linear regression analysis.

Main Take-Away

1. The correlation I proposed about the height of a guy and his girlfriend’s attractiveness has been verified by research which was done more than 30 years ago. 

A huge percentage of life comes down to winning the genetic lottery. The person will go through life thinking that they were the one who used effort to create the success in their life, but success was already 60% pre-determined for them, because they were born in the right time, at the right place, with the right set of genes (tall, attractiveness), in the right conditions (good stable parents in marriage). The famous Investor Warren Buffett is well known for saying that he got lucky in the genetic lottery for being born in Nebraska, ‘white’, and with his type of brain which was designed for asset allocation.

Some people are just born into luckiness. Since they are born with the right genes, with the phenotypical traits that they had, they are almost assured an evolutionarily fit partner. It may not be fair that taller men have better looking girlfriends on average, but that is the way things are in the world.

Here is something that I recently found which will help a large percentage of people which will let them gain about half a centimeter in increase height quite quickly. Something which I have always believed is that getting exercise which can remove the load on our backs and vertebrate bone will lead to some height increases.

I was watching this Youtube video by Dr. Dror Paley when he mentioned the fact that one of the things he does when he is performing surgeon on his patients, but most especially the ones suffering from Dwarfism, or Achondroplasia, is to correct the hyperlordosis that is often most visible in people suffering from dwarfism.

Refer to the Youtube Video “Achondroplasia A Guide For Parents By Dr Dror Paley.mp4”. Notice how the lower back area is curved towards the posterior direction.

When the surgery is being doing, the femur is pushed backwards during the lengthening of the lower limb bones.  Somehow it straightens out the pelvis, and by doing that, it also straightens out the spine.

The surgical part probably doesn’t seem that interesting but the surgical methods doing in the OR doesn’t always have to be. The thing is that if we can look at our own vertebral curves in an X-Ray, almost all of us have the lower back area curved a little. We can do something in our normal lives to possibly correct for those things with some serious dedication.

The study that proves that this exercise would indeed increase height, at least temporarily  – Spine Height and Disc Height Changes As the Effect of Hyperextension Using Stadiometry and MRI

So there are 2 things you can do to correct for lordosis

Part 1

Before the first video, I would like to remind people that I wrote a post maybe a year ago showing that I had found another scientific article showing that the Supine Flexion Exercise would also work to help decrease the load in the back. Refer to the post “Restore Spinal Disk Height And Increase Height Temporarily Through Land Based Supine Flexion”

Part 2

You will need to go to the local gym and use the device which is above. It is known as the Hyperextension Exercises. The machine you will need is found in almost any local Gym. It has no moving parts. You just lie down on it, stomach facing the ground. You just use your lower back muscles or the core muscles to raise the upper torso/body upwards against gravity.

The benefit of these two types of exercises will be more than just a slight increase in height. You will also notice that your mid-section will become smaller, and if you are a guy, a 6-pack of abs. Having a strong back and core from repeated using this gym machine will over time give

I think it was more than 6 months ago when I found certain publications that Dr. Dror Paley had done research to find the effects of IGF-1 on lengthening of muscle. Refer to the post How Muscle Tissue Is Lengthened – Bone Lengthening Will Not Be Limited – Breakthrough!. In that post, I had revealed a Grant that Paley along with other limb lengthening surgery surgeons had proposed to study the effects of using IGF-1 during distraction osteogenesis surgery. (IGF-1 Gene Therapy of Muscle during Distraction Osteogenesis)

In that post, I had proven that the limitation that certain posters on the online forums have set forth, on the inability of muscle tissue to stretch, has also been worked out and had the technical problems resolved. The muscle factor has now been considered and worked around.

What I would propose fro Paley’s research is a personal theory. Here it is…

It might be that IGF-1 does not really help make the growth plates grow thicker and have the chondrocytes proliferate more. What might actually be happened is that the IGF-1 is having the most affect on the muscle tissue surrounding the growth plate, while it is still active.

If we assume that the IGF-1 which is injected into the leg close to the growth plate makes the muscle tissue in that area thicker, which I believe right now could translate to mean longer, then the tension on the bone in the center would decrease.

If we remember the studies which show that “periosteal stripping” would increase the rate of bone longitudinal growth, the surgeons who did those tests more than 100 years ago had suggested that if you just remove the elements that hold the growth plates in place (ie periosteum layer) then the inhibitory factors would be removed, allowing the functional growth plate to expand much more than expected.

If the periosteum is one of those factors, acting like a tough raincoat wrapped around the body which doesn’t allow the growth plate to push outwards, then the muscles which are bound in a certain length could be thought of as the other major factor (maybe also the ligaments and tendons that are connected to the bones might have also an effect).

Since the IGF-1 would increase the muscles, and thus make them longer, as Paley suggested, maybe the growth plates would feel less inhibited by that factor, and the bone in the middle of a limb grow longer as a result of the growth plate having the chance to push outwards a little more.

Comparing “races”: Based on the idea that different “races” have different levels of IGF-1 that is stimulated during puberty, I would even make the guess that the people who are African Americans have increased IGF-1 stimulation compared to the other race groups. (Refer to “Growth Hormone and Weight Gain in African-American Girls“) Studies show that the african american community have around a 15% increased rate for developing Diabetes Type II since the African American children have higher blood insulin levels.

From the study “Relationships Between IGF-1 and IGFBP-1 and Adiposity in Obese African-American and Latino Adolescents” I refer to the following passage…

” It has been shown that Latino and Caucasian prepubertal females have lower IGF-1 levels compared to African-American females (16,20). Other studies have reported positive correlations between total body fat and IGF-1 concentrations in Caucasian children (21,22) and our laboratory demonstrated a positive relationship between IGF-1 and body fat in African-American and Caucasian children that was not explained by diet, physical activity, socioeconomic status, or adiposity”

Does that mean then African American’s would end up taller than other races since the IGF-1 level is slightly higher? Not really, since we need to realize that the natural physiological way for IGF-1 to even be developed is for it to be converted from HGH in the pancreas. HGH does make the chondrocytes in the growth plate divide faster, but the HGH also speeds up the senescence and maturity of bone. Also, IGF-1 can also be sourced from other areas of the body besides just the organ where HGH had the transformation.

So at the same time IGF-1 would cause the muscles to “loosen up”, the elevated GH levels in the system would also speed the body towards ossification. This phenomena is noticed when we see the data showing that on average, African American Females start puberty about 0.5 years earlier than their Caucasian American counterpart. However, the age at which the body stops getting taller would also be earlier as well.

Mathematically speaking, if we say that the duration of puberty is the same for black and white adolescent, from 10.5-17.5, and 11-18 respectively, then it would mean that the ‘white’ groups would on average end up slightly taller, since they had about an extra 1/2 of a year to grow on average. Then when we add in the factor that elevated IGF-1 rates might give the growth plates more growing potential during a short duration of time (from having one of the inhibitory factors removed), in the peak puberty years, then it might turn out that on average, “white” and “black” americans would end up almost exactly the same in height when we average out the entire population and truncate the outliers.

The end result is that while the adult height for the two ethnic groups eventually end up to be almost the same, the adult African American ends up having a higher BMI from a higher adult weight, which is positively correlated with the levels of IGF-1 as detected when they were still an adolescent.

The more research I do on the possibility of getting the Lab grown cartilage implantation to work, the more and more it seems that the possibility is more and more true. I recently found another article showing how researchers in labs around the world have gotten the cartilage to be grown, and quite easily, using 90s printers. (source: http://www.nytimes.com/2013/08/20/science/next-out-of-the-printer-living-tissue.html?pagewanted=2&_r=4&ref=todayspaper&)

A Daryl D’Lima, who is the head of an orthopedic research lab at the Scripps Clinic, has already succeeded in getting bio-artificial cartilage from extracted bovine tissue.

First, he and his team succeeded from getting an old inkjet printer (a 1990s-era Hewlett-Packard printer, a Deskjet 500, with bigger nozzles, a thermal inkjet printer) to put on layer upon layer of a gel containing the cells that cartilages are composed of. The ideas was to replace the ink in the cartridges with their cartilage-making mixture, which consisted of a liquid called PEG-DMA and the chondrocytes. (This I am assuming is from bovine sources).

Second, he and his team have also gotten some bit of cartilage that have been extracted from people who have already gone through knee replaceent surgery.

Like any good researcher, he is cautious in his optimism, and the speed at which his research in the lab will be viable to be placed in the market for the general public to use. Technically speaking, the process might still need to be perfected a little, but it seems most of the challenges at this point is beauracratic in nature, (ie conduct clinical trials, and getting regulatory approval)

D’Lima’s hope is to have just a printer in the OR one day right next to the surgeons. It will… “custom-print new cartilage directly in the body to repair or replace tissue that is missing because of injury or arthritis…”

This device that D’Lima’s team have build is not really like the 3D Printers that are conventionally used in manufacturing companies like PLA and ABS. This bioprinters print cells, but what is actually extruded through the extruder head is a gel or liquid medium. The gel medium would eventually act like the extracellular matrix of the cell, and that eventually turns into living tissue.

When we look closer at the possibility of pushing the cells in the gel medium through the 3d bioprinter’s head without killing the cells, it seems that the cells did indeed survive. The heat pulse was so rapid that most cells survived the process. (Important thing to remember: There is actually two main ways to get the tissues made. The 2^nd approach on making living functional tissues involve starting with a scaffold first and then adding cells into it.)

The advantage of using a bioprinter to print layers of gel and cells on top of the previous layer is that with the bioprinter, it can control the placement of the cells to be similar to cell layout and overall cell structure and aligment of natural cell arrangements. Remember that to have a cartilage to work like a natural growth plate, the cells (chondrocytes) will need to be stacked on top of each other in a “column” like structural alignment.

What we do have in terms of bad news is that we probably will not have the bioprinters making functional hearts in a few years though. That might take more like 20-30 years. The company Organovo is mentioned again. Thomas Boland, a researcher at the University of Texas has still been able to say that the future is in regenerative medicine.

It does however say that when it comes to the cartilage tissue, it is much easier to bioprint than most other tissues. Dr D’Lima says the following “… cartilage might be the low-hanging fruit to get 3-D printing into the clinic”

The reason why cartilage tissue is easier than the others is because it is simpler. The chondrocytes in the ECM is actually quite low maintenance. The cells don’t get their nutrients through blood vessels, but through diffusion through the ECM.

Here at NHGH I will be the first person to acknowledge that what Dr. D’Lima is trying to create is articular cartilage for the ends of bones, not epiphyseal cartilage types, although at the structural level, they are the same thing. Articular and Epiphyseal cartilage are both hyaline cartilage. We want to get epiphyseal type hyaline cartilage created, which will be implanted between two bone segments.

The natural growth plate or epiphyseal cartilage does seem to get its main source of nutrients from blood vessels, that run to the epiphysis and the metaphysis. That might be a technical challenge if we tried to shift the expected functon of the cartilage we are bioprinting to not just stay in cartilage form (for treating articular cartilage damage due to osteoarthritis) but to eventually grow volumetrically and push overall to become longer and make bones longer.

What is good to know however is that the body naturally produces chemical signals that would cause the local area of an osteonomy (bone cut) to start to develop vascularization. Over time, blood vessels will automatically grow into the cartilage implant. This process is however slow.

Growth plate regenaration has been covered before here and here.  Ultimately, this provides more evidence that the presence of germ immature cells are the key limiting factor in creating new growth plates.  Thus our primary focus should be on developing mechanical and supplemental methods that alter the structure of cells to be more like these growth plate chondrocyte precursor cells.

Regeneration of the Growth Plate

Pdf-growth plate regeneration

“The occurrence of growth plate regeneration has been doubted. However, in 5 different series of experiments reported between 1950 and 1986 regeneration of injured parts of growth plates in long bones of rabbits and pigs could be demonstrated. The 1st series implied partial X-ray injury of growth plates in rabbits aged 3–6 weeks.The 2nd series implied autotransplantation of the head of the fibula in rabbits aged 10–21 days. The 3rd, 4th and 5th series implied transplantation of autologous fat grafts into provoked defects of growth plates in rabbits and pigs. The findings show that regeneration of a growth plate occurs when a part of it is injured in such a manner that a bone bridge is not formed between the epiphysis and the metaphysis. Regeneration of a plate is much faster in relation to the growth in length of the bone in the rabbit than in the pig. The 1st and 2nd series suggest that regeneration takes place by interstitial proliferation of cells from the germinal layer of the uninjured parts of the plate. Signs of partial regeneration of growth plates have been seen in radiographs after operation for partial closure of growth plates in children. ”

Growth plate regeneration refers to the healing of damaged growth plates but if we learn the mechanisms by which growth plates are repaired we could potentially use those mechanisms to create new growth plates.

“Microscopic examination showed that injured portions of cartilage were pushed aside by the unirradiated carti­lage growing into the irradiated area transversely in rela­tion to the axis of the bone. In several experiments defor­mities and radiolucent foci appeared which showed similarity to those seen in dyschondroplasia{ectopic masses of cartilage}. When one  half of the distal  growth  plate  of the radius  had  been  irradiated then lagging  behind of  ossitication could  be demonstrated after 9 days.”  Part of the injured cartilage was left behind in the metaphysis as the bone was growing.  Another part adhered to the bony plate of epiphysis.  In between, there was what appeared to be normal growing regenerating cartilage.

2nd series. Another set of experiments describes growth plate regeneration via interstitial growth.  This type of growth would be very promising in terms of inducing adult height growth.  No perichondrium and no zone of ranvier ossification groove was present.  So there was no pool of typical growth plate progenitor cells.

“The regeneration seemed to take place from the viable parts of the germinal cell layer.”<-Bone and cartilage tends to come from the mesodermal layer.  But mesodermal cells implies the type of immature cells like embryonic stem cells.  But perhaps the right mechanical forces can still induce more adult mesenchymal stem cells into becoming more immature cells and into pre-chondrocyte growth plate cells.

“lt is generally accepted that interstitial latitudinal growth occurs in the very young animal, when the germinal zone cells of the growth plate are adjacent to a largely cartilaginous epiphysis as the tissues are plastic.”<-Plastic refers to irreversible deformation rather than elastic deformation where the object returns to normal.  You can get plastic deformation in adult bones it’s just much harder.

Later the study states that interstitial growth can still occur even against a more rigid epiphysis as long as the germ cells are present.

Occurding to Figure 16 area C, the germinal cells look much like resting zone cells.  We’ll have to study how much LSJL and other mechanical stimuli can induce mesenchymal stem cells to be more like mesodermal germinal cells.

A Mechanical Jack-like Mechanism Drives Spontaneous Fracture Healing in Neonatal Mice

“To study the mechanism underlying spontaneous regeneration of fractured bones, we left humeral fractures induced in newborn mice unstabilized, and rapid realignment of initially angulated bones was seen. This realignment was surprisingly not mediated by bone remodeling, but instead involved substantial movement of the two fragments prior to callus ossification. Analysis of gene expression profiles, cell proliferation, and bone growth revealed the formation of a functional, bidirectional growth plate at the concave side of the fracture. This growth plate acts like a mechanical jack, generating opposing forces that straighten the two fragments. Finally, we show that muscle force is important in this process, as blocking muscle contraction disrupts growth plate formation, leading to premature callus ossification and failed reduction.”

“The ossification of soft callus bares similarities to the process of endochondral ossification during skeletogenesis”

“another type of growth plate known as synchondrosis{these do fuse though} is located between the bones of the skull base. The synchondroses exhibit a remarkably organized structure, as each consists of two mirror-image growth plates facing opposite directions. These growth plates are fed by a shared resting zone located between them. The formation of double layers of prehypertrophic and hypertrophic chondrocytes drives growth in opposite directions, leading to expansion of the skull volume”

“the growth plate must also be able to generate considerable forces. Indeed, studies in various animal models as well as in humans suggest that the different growth plates can generate forces that range from the equivalent of 40% to 200% of body weight”

“an active bidirectional growth plate is formed at the concave side of the callus to mediate bone growth. This finding strongly supports our hypothesis that bone growth by the bidirectional growth plate generates the force required for the movement of the two fracture fragments during reduction, similar to a “mechanical jack” mechanism.”

“Expression analysis of SRY box containing gene 9 (Sox9), Col2a1, and Col10a1 revealed that the absence of muscle contraction led to symmetric chondrogenesis and loss of the bidirectional growth plate organization”

“in the absence of muscle contraction the callus fails to organize and act as a growth plate and undergoes early ossification”

“all of the characteristics of an active growth plate exist in the callus at the concave side of the fracture site, including gene expression profiles, cell proliferation, and bone growth. We therefore argue that the growth plate in the callus serves not only for intermediate stabilization, but also to actively promote bone reduction. However, unlike the epiphyseal growth plates and similar to the synchondroses that mediate cranial base expansion, the bidirectional growth plate at the fracture site drives growth in opposite directions. This generates force that moves the fragments toward straightening in a mechanical jack-like effect.”