Me: After going back and reading on my old posts on the power of possibly using BMPs to induce chondrocytes and also heal and regenerate articular cartilage, I have created a new idea on how it might be possible to induce longitudinal growth using a combination of at least 3 main ideas I have been exploring for the last 3 months. This a culmination of all of my learning and research so far. You can see from another post way back entitled” Increase Height Through Surgical Method By Cartilage Harvesting And Chondrocyte Implantation With Growth Factor Injections” that I tried also at that time to think up a possible height increase less invasive surgical path as well, but this new method is more likely to work out and the procedure is more detailed, due to new understanding and research. 

Note: One of the biggest issues we have to understand is what exactly are the differences between the articular cartilage found at the end of the long bones and the original growth plates we had. Remember that both of these cartilage ar hyaline to begin with. The major differences are…

1. The epiphyseal has a perichondrium, the articular does not.

2. The epiphyseal cartilage is created from two centers of ossification, a primary and secondary. The articular cartilage does not.  This means that the epiphyseal is directly connected to layers of trabecular bone which house progenitor cells on both sides. The articular does not.

3. The epiphyseal has a resting zone area, the articular does not.

One idea I originally thought about is try to get the articular cartilage to behave as much like the growth plates as possible.

Note: The other big thing we would have to get right is the right growth factor combination. At this point I am guessing to use BMP-7 (obviously), TGF-Beta2 & 3 (since there have been articles that showed that BMPs need it to work out), BMP-2 since it is the only other BMP that leads to chondorgenesis. We want to avoid BMPs which give better results for osteogenesis but have shown to result in chondrogenesis. The other big one I wanted to use was GDFs which are growth differentiation factors. 

So Step 1…

You create two chondral defects through the knee which connects the inner epiphysis trabecular bone with the articular cartilage. This can be done through two holes punctures through the cartilage of a bend knee (from diagram above). The puncture can be just 2-3 mm in diameter (from study 1). I would suggest using a diameter of 4-5 mm if that is possible. The exact location the punctures will go through will be the trochlea and the femoral condyle (from study 2). The penetration will be through the hard bone, into the epiphysis until it reaches the axis distance where the original epiphyseal plates will be (from X-ray).

Note: From this diagram on the right it suggest that even after the epiphyseal line is gone, there seems to be still a band of trabecular bone which might be slightly thicker and denser in the area where the epiphysis and metaphysis are connect than in other areas in the inner bone. That is the line you want to reach, but right before you hit that thick band of dense bone. 

Step 2….

You implant a type of capsule which has a specific mixture of  growth factors that focuses on chondrogenesis, not osteogenesis. The growth factors can be encapsulated in a collagen and proteoglycan mixture. It is essentially cartilage matrix with growth factors inside but no chondrocytes. The mixture will have BMP-7 and BMP-2 which has shown to help differentiate the progenitor cells in the right way to give you the type of cell desired . You want to avoid types of growth factors which are mainly osteogenic.

We know that adult marrow is mostly yellow marrow of adiposytes and fatty acids. Study 5 suggest using instead BMP-6 and TGF-Beta 3 to convert them into chondrocytes. Remember that the bones are one of the tissues that regenerate and heal the fastest. That means that one must focus less on bone healing and more on how to get the cartilage to expand.

Step 3…

After the implant capsule of growth factors, you implant another capsule that has chondrocytes encased surrounded by a perichondrium layer. This is actual growth plate cartilage grown in vitro. I have researched one study that has shown that in vitro growth plates have been developed and can be reapplied back to function properly in vivo. Study 3 showed that chondorcytes can be differentiated from using perichondrium with BMP-7 so this step should be easy.

Step 4…

You make a cut around the outer edge of the long bone right at the distance where the initial penetration was done. You remove 3-4 mm in thickness axially of outer bone which will be the periosteum but also 4-5 cm radially inward. This is to remove the outer hard cortical bone. The other reason you want it to be at least this thick, is to prevent bone repair. If the created fracture was any thinner the bones will automatically heal over it. You implant resting zone progenitor cells in these locations which are surrounded in cartilage which is themselves surrounded by perichondrium.

Step 5…

A type of gause wrapping with BMP-7 and other growth factors in it which promote chondrogenesis is wrapped around the incision location and the cartilage implant. This has two functions. One is to prevent the cartilage inside the epiphysis to push out laterally. The other is to be a source of more growth factor to get the outer cartilage implant to push inward.

Step 6…

You fill up the original knee chondral defect first using a type of ostegenic BMP like 6 or 9 with TGF-Beta 3 (study 5), and later use a chondrogenic growth factor like BMP-7 which has shown to regrow the articular cartilage (from study 2).

Step 7…

What this method have effectly done is removed every single contraint the long bone has which would restrict longitudinal growth. We learned that the compressive strength of long bone is from the calcium hydroxylapatite in the inorganic matric which leads to the hard dense cortical bone to have a youngs modulus yield of upwards of 150 MPa. The tensile strength is from collagen fibrils arranged in lamellae (source is from previous post HERE). This is around 100 MPa. Since step 4 means the hardest material is fractured at a level which the body’s natural osteogenetic, most of the high value of young’s modulus tensile strength from the intact long bone will be gone. It will be just the trabecular bone which is holding the bone attached in that location and that can be stretched relatively easily by the chondrocytes if they go through hypertrophy.

If we remember, the way that the original ilizarov method works, and how distraction osteogenesis works in general is from callus distraction, which means you pull the trabecular bones apart over time. What is great about this method is that Since step 4 is done in the thicker area, you should not need the fixator to hold things stable unlike the ilizarove method, where the fracture created makes the long bone very weak and can break in half since the fracture was made around the middle (or diaphysis) of the long bone. This is one of the reasons you needed an external fixator to keep things stable and fixed so the inner bone which you had not separated wouldn’t move, causing deformities.

Step 8…

What you have done is basically created an entirely new growth plate similar to what the body’s original prenatal ossification development was like. Remember that the growth plate was formed from two primary ossification centers, My idea is to create two places which sort of goes through chondrocyte proliferation embedding into the bone matrix in the ossification process which will eventually come together fusing into another growth plate in the inside of the lone bone which is around the same location as the natural one.

If you have studied physics you might remember the calculations you have had to do for electrical fields or magnetic fields of a type of 3 dimensional body form called an annulus. I am treating the long bone as a concentric annulus. where the outer most circular region has cartilage implantation and the inner circle has cartilage implantation. The growth factors from both the inside implant and the outside implant  will diffuse into the surrounding bones turning any adult fatty acid marrow MCSs into chondrocytes. If that is sustained, the osteoclasts can clean up most of the dead bone lucanae. If the calcium crystals are hard to remove, we can swing the PTH/TH control so that calcium can be removed from the bones and goes back into the blood stream.

Any expansion the implanted cartilage will do have to move to the state or postion of lowest resistance. Since the lowest resistance is the area where you have made a fracture and implanted cartilage, the inner material will get pushed out. Since you are holding the outer edges intact, the force of pressure will push in the longitudinal direction. since the edges of the outer fracture will be moving away from each other.

Sorry if I have no pictures to explain what I mean.

From PubMed study 1 HERE…

Br J Oral Maxillofac Surg. 2002 Jun;40(3):201-6.

Regeneration of defects in the articular cartilage in rabbit temporomandibular joints by bone morphogenetic protein-2.