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    Info - Thank you Info for linking to the paper by Kuhl and others - "Growth on demand: Reviewing the mechanobiology of stretched skin"
    Link https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3758413/

    Anyone up for discussing the aspects of this paper which apply specifically to foreskin restoration?

    My background is in engineering mathematics. I also happen to be now restored to CI 7 or8. I'm interested to try to find ways to make restoration a bit faster than it is at present.
    Last edited by Tormod; 02-12-2017, 02:56 PM. Reason: Edit to include "Info"!
    Tormod

    Looking for a restorer who has a background in human skin cell biology. I'm interested in developing a mathematical model of the restoration process. Personal message me.

  • #2
    Any influence on the process involved in skin expansion would have to be physical, or biochemical. Those two realms encompass what happens in skin expansion (as far as Science knows thus far).

    The actual influences are tension, and what tension does to the tissues physically (which is where theory reins over the known), and biochemical (the flow of intrinsic factors which induce increased mitosis). What I got from reading this paper (and from my University days) is that there isn't a way of somehow end-running the intrinsic biochemical process which results in mitosis at a rate higher than maintenance. Why? Because the process exists in a "sealed" system, as it were. It's natural, there before we thought of expanding our skin; it's built-in.

    And tension is tension. It's external, and it exists as a stimulus only; a stimulus which triggers the biochemical aspect of the process at a tipping point, as long as there is a cessation of tension soon after. It has no other effect. In fact, it has a negative effect if left at a given value for too long.

    The only known influence on that system (the only one that Science seems to know), is indirect, not a direct influence. It is an influence on the inevitable negative effect(s) of a tension load on the supporting organs of epidermal function (blood vessels). With tension, there is an inevitable decrease in blood flow due to tissue deformation (the supplying vessels reduce in caliber) . The biochemical factors are carried to the cells via the circulatory system. So if blood flow can be brought back to some approximation of "normal", then those factors can be carried more effectively. This was a finding revealed by a study which I can't find on the internet anymore.

    So thus far, there isn't anything that can directly affect the process, and only one proven chemical which can influence the process indirectly.

    But what do you have in mind?

    (And I have to say, a mathematical model of mitosis is beyond me and my background, but I wouldn't be surprised if there's something to be found online).

    Comment


    • #3
      Thank you for the reply Info.

      There is no doubt that the biochemistry involved in natural, or in forced, skin expansion is complex. And there are processes which proceed in parallel and others form a chain, and the net result is more skin. Little wonder that the paper does not go into detail about the rate constants of the process! It uses a "normalised" time and is more interested in the form of the resulting skin. (Want more about this?)

      Thankfully, there should be a good blood supply to the penis. Further, we restorers do not surgically insert expanding balloons under the skin. The blood should be able to reach all the parts of our expanding foreskins.

      One obvious difference that penile skin has from general body skin is that it is not strongly attached to the underlying penile structures. It moves. There must be some component missing from penile skin. Maybe collagen? And there is some smooth muscle which is in outer penile shaft type skin. These differences could result in significantly different mechanical properties.

      Don't concern yourself with the difficult looking mathematics in that paper. They are studying changes in a surface. Most of what we restorers need could be modelled using one-dimensional variables. Further, they make many assumptions concerning the numbers and forms of functions.
      That's the start of what I have in mind. There could be more to follow - be afraid!!
      Last edited by Tormod; 02-13-2017, 02:55 AM. Reason: Edited to format paragraphs
      Tormod

      Looking for a restorer who has a background in human skin cell biology. I'm interested in developing a mathematical model of the restoration process. Personal message me.

      Comment


      • #4
        I'm a biologist, but certainly not an expert in skin regeneration, nor have I conducted peer-reviewed research in the field. As has been stated, much more is to be learned about the factors that induce cell division in tissues, including the epidermis. However, there is a fair amount of evidence that has identified a number of internal and external factors that trigger cell division via gene expression within the "cell cycle control system." Much of this knowledge has come about through cancer research.

        Applied medical technologies, such as autologous chondrocyte implantation (ACI), rely on the use of several growth factors to induce somatic (non-dividing) cartilage cells taken from a patients tissues to dedifferentiate into adult stems cells called fibroblasts. The fibroblast stem cells are then used to treat joint cartilage defects such as arthritis lesions by inserting the dividing cells into the lesions. The goal is for the fibroblasts to fill the lesions and develop into mature cartilage cells. I had this done in my left knee back in 2003. I suspect a deep dive into the literature would reveal similar processes at work in skin tissues.

        Again, based solely on my reading of the literature way back in the mid 1990's when I started investigating FR (and designed one of the first adjustable FR devices), I suggested that "density dependent" inhibition was a key factor in FR. As you may be aware, somatic cell density within normal tissue controls division of nearby stem cells. In growing tissue, the replacement ratio is greater than 1:1. In healthy tissue, the ratio is 1:1. And in tissue undergoing degeneration, the ratio is less than 1:1. Cancer cells have gone rogue by breaking the bonds of density inhibition; dividing to produce masses of very dense cells, i.e. tumors. Mastectomy patients who choose breast implantation understand the process of stretching and skin expansion. They have to endure 24/7 inflatable skin expanders for several months so that enough skin is grown and can be stretched over the breast implants. It is very likely that the same processes are at work with FR.

        Hope this contributes to your efforts.
        Last edited by bioprof12; 02-13-2017, 07:44 AM.

        Comment


        • #5
          Originally posted by Tormod View Post
          Thank you for the reply Info.

          There is no doubt that the biochemistry involved in natural, or in forced, skin expansion is complex. And there are processes which proceed in parallel and others form a chain, and the net result is more skin. Little wonder that the paper does not go into detail about the rate constants of the process! It uses a "normalised" time and is more interested in the form of the resulting skin. (Want more about this?)

          Thankfully, there should be a good blood supply to the penis. Further, we restorers do not surgically insert expanding balloons under the skin. The blood should be able to reach all the parts of our expanding foreskins.

          One obvious difference that penile skin has from general body skin is that it is not strongly attached to the underlying penile structures. It moves. There must be some component missing from penile skin. Maybe collagen? And there is some smooth muscle which is in outer penile shaft type skin. These differences could result in significantly different mechanical properties.

          Don't concern yourself with the difficult looking mathematics in that paper. They are studying changes in a surface. Most of what we restorers need could be modelled using one-dimensional variables. Further, they make many assumptions concerning the numbers and forms of functions.
          That's the start of what I have in mind. There could be more to follow - be afraid!!
          Let's make this simple for readers, and relevant to both posts:

          1. I'll start with the bottom line: no point in referring to what current medical practice offers in skin expansion, or in the use of insurance carrier approved stem cell treatment, and especially no point in referring to experimental research. None of this is available to the "real world" of penile skin tugging, and the average guy who's doing the tugging. That is the simple truth of it. So...none of the attendant theories and methodologies transfer to our world. Sorry, just doesn't. That's the point that Distalero used to repeat ad nauseum, and for good reason. Can't get there from here, so I have to ask, what does kicking these areas around have to do with our real world? We don't have the tools, the skills, and the cell cultures available to us. And we never will.

          2. Tension, and tension deformation, is just that, be it from an implanted expander or something which pulls on a pinch of penile skin. Deformation is deformation, so in theory blood flow is at least somewhat compromised when we apply tension. Expanders, though, are a known risk to healthy tissue due to their elevated increased compromise of blood flow. Not only is any new, additional epidermis at risk, so are the underlying tissues. Research knows this, practitioners know this, patients who've experience necrotic tissue as a result, know this, so ... research continues to look at this issue. This is another way of saying, clinical skin expansion is an imperfect art.

          So if that's what you are referring to when you say "blood should reach all the parts of our expanding foreskin", then ok, I'll agree in general. I suppose. But here's the issue with your statement: only a small area of skin (not a "foreskin", but rather penile epidermis left from stripping away foreskin tissue) sees that tension, and much smaller area is stimulated to respond. Absolutely NOT "all areas" are involved. So: a less than perfect scenario standing in the way of a hopped-for end-run, non-existent, restoration method. And of course I'm not including the time it takes your epidermal cells to respond. Again, skin expansion, whomever does it, is an induced and, therefore, technically an artificial scernario, so there is a lag in response due to that; at least as I understand it. That response is natural, but it has to be called up, and skin's other inherent properties will resist the insult until that tipping point is reached, and then released. Takes time; not to get there, but to respond.

          3. Epidermis covering the body is loose. Loose everywhere. No special "loose" quality exists for penile skin. And there is most definitely connective tissue (collagen) under penile skin. So no missing component. Therefore....no significant difference in mechanical properties. This is a good thing, of course: results in healthy tissue, and with reference to the so-called dartos sheath, it brings us tissue which solves the false dilemma of that feared but non-existent 'loose sock" effect. What I think causes some difficulty is how very thin, and discontinuous, this smooth muscle is. Needs to be stained to see it with a light microscope. So you have good properties, and no loophole or edge, which makes end-running possible.

          4. Not sure what you mean by "be afraid", unless you're in the middle of bringing the Swarzenegger cyborg back

          5. I like the conversation. And I like doing the minimal translation needed thus far. What I don't like so much, is being the bucket of cold water, but my thing in any and all of this whole restoration practice is to bring us back to what we can do personally, and how long that takes. And, the benefits that our grassroots efforts bring.

          Limits: nobody likes 'em, but they are right there staring us in the face. The theoretical guys like kicking stuff around, and I like that conversation, as I've said, but I also have to ask, if Science and the practice of Medicine (waiting in the wings), haven't found an end-run, what makes us so sure some garage-guy can? or theory will? Military spends big money (BIG money) on this and other aspects of tissue science. Nada, so far. Think: burn victims. This, gentlemen, is another 900 pound aspect of the "real world".

          So: there's the challenge, or the challenges, plural, for the Henry Ford (assembly line) types. Distalero used to say, skin expansion, for us, is an art, not a science. Perhaps you can see why.

          Comment


          • #6
            Good points. However, I will suggest that while we might not be able to find an "end run", so to speak, but I think we could definitely benefit from a more precise understanding of some of the parameters:

            1) how often should tension be applied in order to maximize the triggering of cells?

            Reports suggest that anything from less than a minute (manual tuggers) to as close as people can get to 24/7. And, I have found literature that suggests that at any given time, about 5% of the cells in skin will be in mitosis. And that a full cellular cycle takes about 1 week. But I have not found anything that says when in a full cell cycle the cell is able to be triggered. If we had that, then we could model that mathematically and identify a timing for triggering cells that would be optimal, at least in theory.

            2) How much tension is needed to trigger cells effectively?

            Reports suggest that anything within reason works, from gentle to on the verge of injury. The literature suggests an amount of tension, however, it is difficult to translate to what we do. And, I have not seen careful studies in the literature that indicate they have sorted the tension levels out, instead it seems more the case that they use maximum tension without too much risk of injury/damage. But if we had the optimal tension level then we could sort out how to translate that for our methods.

            I think that having these two parameters well in hand would be a tremendous advantage. There would be a lot less guess work and a lot more confidence. We could give recommendations with a lot more confidence.

            Just a wildlife biologists musings...

            Comment


            • #7
              Thank you for the comments, men. You now know the depth of my ignorance about human biology. I read the paper again and now note that (Section 1.2)
              "From below, the dermis is demarcated by the hypodermis, shown in white in Fig. 2, a subcutaneous fatty layer that connects skin to bone and muscle."
              So penile skin, at least the outer shaft type, is very similar to general body skin. I had been concerned that any differences are so great as to make the paper irrelevant to our purposes.

              The human body is amazing in its ability to maintain itself. The complex set of biochemistry which senses disturbance and takes the steps to correct it. We grow more skin as we grow, we grow more skin if we eat too much. It would be a folly to try to interfere with the internal processes when we can mimic the skin tensions involved in becoming more weighty.

              Info - you are far from being a bucket of cold water. Some folk see mathematical modelling as a bit of an art. If nothing else, mathematicians are realistic. When faced with a complex set of processes we like to simplify. OK, we guess what seems to be a numerical relationship between the input (mechanical strain) to a system and the resulting output (more skin). We then make numerical predictions based on the guess and check if they agree with the result of experiments. There is more than just that - but, enough for now.

              GregB - Restorers are critically interested in tug tensions and timings. And, of course, in the "years until I get to CI###" In the last paragraph of section 6.3 the authors freely admit to not being able to give reliable estimates for times : "In the current model, the long-term response growing of skin is not yet calibrated in time. We have assumed that chronic growth between two filling increments takes place within a normalized time interval from zero to one. ..."
              They do note some values of rate constant published by other authors. More on this in due course.
              Tormod

              Looking for a restorer who has a background in human skin cell biology. I'm interested in developing a mathematical model of the restoration process. Personal message me.

              Comment


              • #8
                Perhaps a mathematical model that allowed exploring different options?

                If we had variables that included:

                # cells able to be triggered
                # cells in mitosis
                # total cells
                # times per day tension is applied
                # days a week tension is applied

                Then we could at least play with those variables to see how much difference it would make (in theory) with different tugging regimens. It might get us no further, however, we might also find that even with wide differences in expected cell triggering, a single regimen was likely to be most effective. That would be a step forward I think.

                Comment


                • #9
                  Originally posted by greg_b View Post
                  Good points. However, I will suggest that while we might not be able to find an "end run", so to speak, but I think we could definitely benefit from a more precise understanding of some of the parameters:

                  1) how often should tension be applied in order to maximize the triggering of cells?

                  Reports suggest that anything from less than a minute (manual tuggers) to as close as people can get to 24/7. And, I have found literature that suggests that at any given time, about 5% of the cells in skin will be in mitosis. And that a full cellular cycle takes about 1 week. But I have not found anything that says when in a full cell cycle the cell is able to be triggered. If we had that, then we could model that mathematically and identify a timing for triggering cells that would be optimal, at least in theory.

                  2) How much tension is needed to trigger cells effectively?

                  Reports suggest that anything within reason works, from gentle to on the verge of injury. The literature suggests an amount of tension, however, it is difficult to translate to what we do. And, I have not seen careful studies in the literature that indicate they have sorted the tension levels out, instead it seems more the case that they use maximum tension without too much risk of injury/damage. But if we had the optimal tension level then we could sort out how to translate that for our methods.

                  I think that having these two parameters well in hand would be a tremendous advantage. There would be a lot less guess work and a lot more confidence. We could give recommendations with a lot more confidence.

                  Just a wildlife biologists musings...
                  Great post, greg, thanks for reminding us about the facts you've touched on here. They give a general impression of how long it takes for various aspects of mitosis to form and interplay.

                  And as far as a mathematical model goes, using the criteria of "number of cells", etc, which you list above, the use I see in it would be as a general background to discuss complaints of slow growth made by forum members (and, because it comes up from time to time, as a judge of claims which can't be supported by the basics of human physiology). There is bound to be a lot of variation in response, and unforeseen variables, out there, so the model won't serve all (or even many) restorers specifically, but just the presence of a general expectation can be used to drill down to find what any individual is actually doing in terms of device/method/schedule. That way we're all singing out of the same songbook.

                  And it can perhaps serve as a reminder that this thing is slow, and results are definitely not obvious in a day, or a week, or a month. So when I think about trying for a model now, it might just serve as a restoration forum advance. So good on ya Tormod. Maybe not a huge leap, but at least a small advance in forum communication. You and I have been around long enough to see how having no common point, other than (my) dreaded myth (), often fails.

                  Comment

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