Transdermal: Why it doesn't work, how we can make it work.
  • So, in implantable tech, one of the most troubling and restricting challenges is that transdermal implants are a big no-no. The problem with these implants is that they leave microscopic holes in the skin that can allow bacteria to enter. So, forgive me if someone's already working on this and is ahead of me, but how can we get these holes to close? My thinking is that it wouldn't be feasible or smart to have some kind of glue or sealant between the implant and the skin, but I think we could develop some artificial manner in which the skin cells bond to the sides of the implant. I'm no microbiologist, but I think it's possible. What I find appealing about this method is that it takes the human element out of it (or adds a cellular human element, depending on how you look at it). Instead of physically closing microscopic holes or filling them with some paste, the body does the work for you. Here's how I think this could be done:
    1. Figure out how skin cell production is regulated in the body, what chemical and electrical signals need to be sent out to tell the skin to grow.
    2. Develop a material that the skin can bond to that is not permeable, is tough enough to stand up to regular abuse, and possibly works symbiotically with the skin cells to keep their bond strong.
    3. Use the usual transdermal implant procedure (lift skin, poke hole a little to the side, push implant in, slide over, poke hole, pull implant through)
    4. Provide chemical, electrical, hormonal therapy to the skin cells to tell them soup's on and they need to grow onto the implant.

    I'm not saying it's easy or that I've got it all figured out, but it seems like it can be done with some hard work. I don't think step 1 will be so hard, but 2 is a hell of a project. What do you think? Have I forgotten some consideration?

  • Maybe we should examine how animals do it with horns/antlers/etc. The animal kingdom is rife with examples of bony transdermal protrusions, sometimes attached to the skeleton itself, and to the best of my knowledge random infections aren't really a concern.
  • glimsglims March 2015
    If you pop on the slack board, you can see that we have already started working on this project. drjaaz and I are getting ready to do some testing on some prototypes for this very thing you are talking about. It looks like it died, but that's just because we ran into some issues and then started chatting on skype. Pop on over to check out what has been said and I'll make sure that jaaz gets on here and throws up a summary of where we are at.

  • chironexchironex March 2015
    Yikes can a guy not clean his cockroaches habitat in peace for 20 minutes? I kid of course (not about the cleaning i was actually doing that). Ok so the point we are at is this. Transdermal's are not actually as hard as they were thought to be. We're in the process of designing an implant, which functionality aside, is transdermal in nature. So how are we doing it? Well it's fairly simple actually. It works on a series of coatings. The first in our case since actually titanium is bloody expensive is TiN. This will coat the actual piece which will be made of surgical steel. This gives biocompatibility which is always the big and primary concern. With that out of the way we need to tackle how to get the skin to fuse to the implant. This was pioneered by a material called hydroxyapatite also known as HA. Your bones are full of the stuff naturally but by coating the outside of the implant in it, it essentially tricks your body into thinking there is bone there and allows you to fuse to it. Now this on it's own isn't perfect. So we're adding a secondary dip which will be done immediately prior to implantation. The dip is an extra cellular matrix extract which will be freeze dried for transport and rehydrated immediately prior to use. This helps the cells have a matrix to build around as they fuse to HA. That's the gist really. Anything that isn't in contact with the skin tube that gets formed doesn't need the HA so we'll be using PDMS to coat the lower electronic parts. But that coating is variable. I would also suggest having some sort of any microbial coating on the bit the stick out above the skin just to help keep bacteria and such out of the hole as you heal.
  • That's easily the coolest thing I've read all month. Where can I read more about this implant, and where can one find this slack board to keep an ear to the ground on such things? I feel like I'm missing a whole shitton of discussion, I didn't even know about grindfest until it was over...
  • chironexchironex March 2015
    download slack. I think you need an invite via email to join the board which anyone can get just let us know you want one. It's poorly set up in that sense but there are a lot of good projects on there. most are stalled but a fresh set of eyes and ideas could unstall them. Also some have moved to skype and such as some people are running with them, like the transdermal one for example. Once we release our transdermal I presume the tech will be open source and anyone can try for it themselves. could lead to the next gen of implants. I for one have a bunch of transdermal ideas which if this one works I'll move on to.
  • AlternateAlternate March 2015
    Apart from the obvious drawbacks and issues, theoretically, would this implant work in bone as well? I seem to remember some discussion about that in another post, where they quickly came to the conclusion that even if it did work, it wouldn't be all that feasible.

    Edit: What about the false teeth 'anchors' that are used in the mouth? They're transdermal - how have there not been massive complications with them? Unless the gums seal more readily around the post than skin would.
  • Wow. When I posted this, I thought I was WAY out of left field, but it sounds like I came up with a pretty similar solution to your guys' experiments. Damn. I guess I'm not as dumb as I look.
  • chironexchironex March 2015
    If anything it would work better in bone. HA comes from bone originally so the osteocytes will work on it without issue. Not sure about the teeth thing, never looked into it.
  • chironexchironex March 2015
    Also for those who want a slack invite, message glims, not me. I'm not admin and can't add people.
  • FrankFrank March 2015
    How are transdermals achieved in routine practice? 

    E.g. long term IV plugs in comatose patients, and particularly cannulas fitted to cows - those are portholes right into the digestive tract!
  • FrankFrank March 2015
    I mean, look at these guys, they made a transdermal from a bloody plastic drinks bottle!
  • Uh, that was into a sheep. And as you can see from the pictures, it hernia'd like a mofo. They weren't that careful with that thing.
  • Plus the people operating were actual doctors and they had an entire operation.
    "Preoperative preparation: -

    Food was withheld for 24 hours, while water was withheld for 12
    hours, prior to surgery and the left para-lumber region was prepared for
    aseptic surgery. The operation was carried out in recumbent position
    and the operated animals were positioned on the right side.

    Anesthesia: -

    Operated animals were injected intravenously with Diazepam 0.5% in a
    dose of 2 mg/kg Bwt. and 10 minutes later, animals were injected,
    slowly intravenous, with thiopental sodium 2.5% in a dose of 10 mg/ kg
    Bwt. (Abdel-fattah, 1999)."
    The sheep lived for 16 months after operation. Rams live to about 10-12 years old. These lived to an average of 6.
  • FrankFrank March 2015
    @FrankMatheson - Isn't a cannula essentially a hernia, with an opening? I don't understand how it couldn't involve a hernia.

    Also I don't think the rams died after 16 months - that was simply the follow up period of the experiment - during which the authors note that the rams were in good health. 

  • glimsglims March 2015
    These things usually require constant care and attention. Imagine the First 3 days of aftercare for an implant, forever. Even transdermal piercings and the like require constant uptake and maintenance and many of them grow out eventually.

    IVs are maintained daily and it's not like that person is out and about, climbing trees and the like... If we put you in a coma, there are a lot of things we could do to you. It doesn't mean it would work on a standard moving about person.
  • FrankFrank March 2015
    @glims What counts as transdermal when it comes to piercings? I have a labret stud that's been happy as larry for 10 plus years now; my ear bars (which would seem less invasive) are much less settled.

    Punching a hole in the skin seems to work OK long term in other applications - even when going through several tissue types, as in the case of a rumen cannula. Is it simply a case of picking a stable insert site? Guess what I'm asking is whether transdermal is inherently problematic because of the tissue, or simply difficult to maintain without banging/ripping.

     
  • In my short hospital training, IVs were maintained every couple of hours. And even then, they're just tiny needlepricks, not gashes or rectangular carvings out of the skin. Transdermal implants are even pretty frowned upon in the (official) medical field. If something needs to be an interface between the inside and out, like a PICC line, they generally implant the full thing and then only access it through needles.

    Regarding the lifespan of the rams, I suppose it's a little bit up to interpretation, but
    "It has been successfully used in rams for 16 months without complications." sounds to me like they had complications at 17 months and
    "...fistulated animals maintained functioning satisfactorily for about 10 months..."
    sounds like the animals died or became dysfunctional at about 11 months. I don't see anything in the study that tells us if they intentionally did the experiment for 16 months or if that is just how long the animals lasted.

    Regarding the "hernia", I was mistaken in thinking the swelling in figure 6 and 7 were complications, but that was actually the Rumen (sheep organ) being pulled out so it could be worked on before being reinserted.
  • chironexchironex March 2015
    K transdermal is different than a piercing. When you get a piercing although you do have a bit of metal sticking out of you a tube of skin eventually forms around it. So there's no contact with the outside world. A transdermal would be something like a microdermal on someones arm. It's anchored under the skin and leaves a hole open to your body that bacteria can get in.
  • The sheep lifespan thing reminds me of this really famous psychology paper about conditioning where psychologists conditioned this kid to be afraid of rabbits. People reference it all the time in official documents and stuff saying "and little Billy Bobby Johnny is still afraid of white fluffy things to this day". Except that kinda ignores the fact that Billy Bobby Whoever had a rare disease as a child and died right after the experiment. So people go on and on all day about the long term effects of something that had no long term effects and could therefore not possibly be fully studied.
  • Are you referring to the Little Albert experiment?

    https://en.wikipedia.org/wiki/Little_Albert_experiment
  • That's the one!
  • CassoxCassox March 2015
    Ok. So IV access is normally good for 3 days. After that, the risk of phlebitis increases significantly. This isn't any huge risk in a normal population; the point is simply that the lifespan of an IV is self-limiting. It will stop working.

    A PICC line was mentioned above.. much much better. It's a catheter that snakes up through a major vein and sits near the S. Vena Cava (right side of the heart basically). Properly maintained they can remain in a person as long as a year. Maintenance really is daily though and for such long term use they are usually heparin locked rather than saline.

    The GI access stuff discussed above is used in humans all the time. A Gastric tube passes right through the abdominal wall to the stomach. An actually tube like opening forms too. The inside of the stomach/duodenum etc.... isn't actually "inside" the body though. This is really more like a really big earing. The GI tract is a tube of "outside" running through the body.

    The "transdermal" we are really discussing here thought is essentially something sitting subcutaneous. The issue isn't whether or not it's doable. I put in 12 micros for a NMS project. The issue is how long they last, how much care is required, and how delicate and limiting placement is. I've lost 3 damn micros and had to replace. Two were because of placement where my work scrubs rub and the other was from tackling Glims and having it rip right out. Now if these things were being used as an access point for an implanted device... I'd be very upset. So, we need to improve the design...
  • I didn't realize there was a mechanical problem as well as a microbial one. What if the implants were flush or near-flush with the skin?
  • chironexchironex March 2015
    We're aiming for near flush with ours but the problem is that flush comes with it's own problems. If the skin swells it can cause the thing to get healed over. It's better if it either sticks out a bit or has a cap that prevents the skin from covering over it.
  • Yeah, I was thinking of the magnet transdermals people always want to do and attaching a magnet flush would bring all kinds of pinching problems so near flush is best.
  • V10latorV10lator March 2015
    Somebody with enough knowledge should really look into the teeth things, they implant so much things into the mouth (fun fact: They even use transdermal magnets so a teeth prosthesis sticks better) there must be something special.

    Maybe some day we'll just have the cables get out of our nose: Exiting the body in the mouth, then going through the air canals to the nose. Nah, just kidding but some people have stretched piercings at their cheeks, for example. Wait... If we exit in the mouth and use healed cheek piercings holes to get out of the mouth?

    Hope this helps you guys a bit with brainstorming and if you ever need a testing rabbit feel free to ask me. :)

    //EDIT: This image is from Wikipedia, showing an anchor for braces - for
    me this almost looks like a cable plug.
    image
  • zeon66zeon66 August 2015
    Hi all new to this but recently heard of this thing called vetigel that mimics the cell structure of the skin im not sure but maybe it could be used to solve the microscopic holes  problem (not sure if its 100% the answer but might be part of it)
    Hopfully ive help point some one the right way if not please can you explain how this wont work
  • glimsglims August 2015
    This is interesting. Paraphrasing- a plant based polymer with a fixative spray.  Basically sounds a lot like agarose with a calcium chloride crosslinker to make a more stable hydrogel... of course, there has to be more to it.

    It's hard to say without access to the gel, but your inital problems would be the same I believe. You would still have that edge, it would just be covered. however, the covering itself still has an edge, if that makes any sense. Even if the gel blended seamlessly with the skin, it wouldn't blend with the implant. The surface of the implant needs to be functionalized the make that transition state.  That is what we are working on now. However, I am still interested in getting my hands on this. Any veterinarians around?
  • zeon66zeon66 August 2015
    so this stuff could be useful but only as a temporary seal? and from what ive heard its extracted from plants to make use of they very similar cell structure to the skin but in theory shouldn't we be able to make it a solid coating around whatevers protruding out the skin (my thinking here is that the skin will be able to heal and seal itself fully around the coating because its structured the same) either way im guessing its either designing the protruding part to seal itself or somthing thats going to come from the same/similar production of this vetigel . ill look into it more because i reckon the only thing that would work well will have to mimic human skin so it can truly seal
  • chironexchironex August 2015
    We already have a material that allows the skin to fuse to the implant and close the gap. We're in the process of testing it but if you can find other materials by all means. But from what I could tell vetigel won't work. But feel free to prove me wrong. There's a small peptide that has shown some sucess but the hard part is binding it the surface of the implant in a way that keeps it functional. So ya there's a few materials out there and you've got the right idea. You need a material that the body THINKS is a more body and give it something to physically attach to.
  • sparhawk817sparhawk817 October 2015
    @glims basically zeno's paradox. there's always an edge. too bad we can't anchor directly to bone... titanium mesh and some 3d printable materials(high tech labware, not home grown repraps) are used to influence and support bone growth, if we had a way to grow the bone around our transdermal, say a usb port, but made sure it didn't cover anything it shouldn't have... idk. just spitballing
  • glimsglims October 2015
    We're not using a plant extract. We're using a purified human extract (lab grade, not home made). The _theory_ is that the skin will actually grow onto the coating which is bonded to the implant.  The skin barrier is always the issue. Technically, there isn't always an edge. There are lots of situations where this is true in nature. What were are going for is more like a transition state. We'll see how it goes....
  • chironexchironex October 2015
    Ok here are the first pics of our first prototype shell. It's for testing purposes only, just testing the strength of the coating. It's coated in a 20nm layer of gold. I'll be stuffing it into a bit of chicken and whacking it around to see how the coating holds up. I'm still working on a better coating but this lets us at least move forward a little. 
    image
    image
  • glimsglims October 2015
    I feel like for some reason that it should clarified that this is just a coating test. obviously that classy crimped end is not a final thing. Y'all remember that hideous block that I had in my arm a few months ago? This is the house for that.
  • MagneticJacobMagneticJacob October 2015
    Could someone pist a link to that "hideous block".
  • glimsglims October 2015
    http://forum.biohack.me/discussion/899/test-implant-0422


    Testing it one step at a time...
  • glimsglims October 2015
    Oh and update on this gold coating. It's too thin and didn't adhere. Ish came off when force was applied. Gold no good. Using titanium.
  • FrankMathesonFrankMatheson November 2015
    Any news?
  • glimsglims November 2015
    @chironex is swamped with school. So, it's me again. HA coating has been applied on top of titanium. Voltage was too high, so it looked like synthetic coral. Which is cool, but not what anyone is looking for in this case. Waiting on some chemicals to reduce cost of process, adjusting voltage, etc.

    There's kind of a self imposed deadline (jan1) on this so expect it to take as long as it takes, but not to take forever.
  • OniExpressOniExpress December 2015
    To be fair, I'd be interested in seeing what the too-high-voltage results looked like, not to mention rundown of it's physical properties.
  • FrankMathesonFrankMatheson December 2015
    Same. Unless it detracts from other more pressing matters. At least a picture would be cool, if you have one.
  • glimsglims December 2015
    It looks like coral. Like foamed rock.
    He's off trying to make it into a paint now...
  • chironexchironex December 2015
    http://forum.biohack.me/discussion/1176/hydroxyapatite-electrodeposition-for-transdermal-implants#Item_5 I posted a whole video going through the process. also it's less porous in the coral sense and more in the "the titanium was eaten away by the voltage" sense. Now working on a silica-HA composite so we could just paint on a layer instead of the electrodeposition. almost got it working too. The layer is a bit flakey atm so gonna try heating it to a couple hundred (800~) degrees to really melt it on there.

    totally dry 
    image
    image

    When mostly dry:
    image


  • chironexchironex December 2015
    I got the paint working properly. I screwed up the coating cause it got too thick before i'd coated it all so I only managed to properly coat portion. The coating is hard as a rock. Hit it with a hammer and it didn't budge. Sanded off the surface to expose the HA. It looks rough but it's actually super smooth and I can sand it with 1000 grit and it just gets shiny. I need to make a better more pure and clean batch of HA and then mill it with the sodium silicate so there's less specaling and a more uniform coat. That said the HA particles are pretty small so even areas that look grey are actually full of HA. I may give it a further treatment after coating to make it more hospitable to the host. Eitherway this is a really cool paint. 
    image
  • chironexchironex December 2015
    Finally think i've got this finished. It still needs a little bit of work but thus far all is going well. 

    Roughed with 60 grit for better adhesion of coating
    image

    Fresh after painting, rough and bumpy.
    image

    Dry but not polished
    image


    Polished and almost done
    image

    image


    under a scope 

    image

    Flat face of coating, you can see all the bits of HA 
    image
  • glimsglims December 2015
    I'm terrified. And excited.
    Hows the internals looking. Or are we, at this point, building an arm cave. I'm ok with arm cave, I'm just clarifying.

    Also, before anyone else says it. Those edges look brutal
  • chironexchironex December 2015
    Picking up parts for internals today. The whole thing should be finished by end of day. Fixed edges. There are a few small crack cause of how it dried so gomma give it a spray with dilute silicate to fill any and then sand it smooth again.
  • kuroro86kuroro86 December 2015
    It is possible to have the picture made smaller to be albe to see the full ? I see them huge 
  • ChilliEyeChilliEye December 2015
    Try refreshing the page.

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