We saved two babies’ lives with a 3D printer. Ask us anything!

Hi Doctors,

I'm a Michigan Engineering student and I'm currently taking a class on Global Quality Systems and Regulatory Innovation (BIOMEDE 599).

I saw that you received emergency clearance from the FDA to implant both Kaiba and Garrett. How will the FDA and related regulatory bodies affect the way this process is used in the future? Have you run into any interesting regulatory roadblocks while developing this?

Go Blue!

3D printing will be a challenge for the FDA as you obviously can make custom implants and can readily change design. This raises issues about how to implement FDA quality systems requirements (QSR). Also, how do you verify and validate such processes? These are challenges that we face and will require new approaches in regulatory science. I think the most interesting challenge is how to implement QSR for 3d printing. Thanks for your question. Scott Hollister

A follow up question to this: what would've happened if the FDA hadn't approved of the procedure? Are there other routes that could've been taken, or was this a half court shot at the buzzer?

The children would have died without intervention. Unfortunately, we have had other potential candidates that have died before we could. This is the toughest part of this disease and why I am grateful for my collaboration with Scott. GG

What would have happened if the FDA had denied it and you'd implanted them anyway?

No. The long-term effects of ignoring regulatory requirements would have been way too costly. It really would shut down the possibility of helping more children in the long term. But the FDA has been extremely helpful. GG

What were the specific, technical, unanswered MEDICAL (as opposed to legal) questions that led to the FDA's reluctance in those earlier cases (if that was, indeed, the obstacle to intervention)? Contra-indications and side-effects etc.?

Was it a case of - "We don't know how this might backfire yet", or simply a case of the customisability of the implants? How is the latter different from the approval process for a new drug? After all, every patient is different, and they come with different dietary and exercise behaviours, medical and genetic histories etc. The same drug is varyingly effective in a sample population. So, is the approval process simply a matter of the experimental therapy racking up an arbitrary number of "successful" cases in a clinical trial, that would put a judge's mind at rest - about the statistical probability of success?

TL;DR - Could you list the "good reasons" for the existence of the FDA's long and rigorous regulatory process? I'm sure they have quite a few.

Also, you've already talked a bit about how you managed to get verification/validation. Did you have to implant a splint in a cadaver's trachea, and hook it up to an external respirator? To ascertain the mechanical stability in (simulated) vivo ?

We never had an obstacle from the FDA with this. The people who manage approval at insurance companies have at times been unwilling to pay the money to have someone sent across the country for a non-FDA approved device even if it would save them money, and there is no alternative. It took a lot of phone tag to finally identify the people and mechanisms for clearance to place the splint. Even identifying who would be willing to take on the different parts was not straightforward. Actual approval is based on a scientifically valid and carefully observed trial with specific protocols that have been vetted before initiation. The full writing and vetting of the protocols is what we are doing to initiate the trial now. The FDA plays an important role in providing a certain amount of safety for the public in the use medical devices.
GG

We are here, in Mott's PICU, do you think that there is anything significant you can do with a 3D printer to save my son's life who suffers from Spinal Muscular Atrophy Type 1? This is day 130 in the hospital, he is 18 months old. Trach/Vent dependant, as well as g-tube, etc. We are desperate for help and answers. We are unable to hold him 99% of the time, and movement also causes him to desaturate, or go bradychardic.

There is a lot that can be done for children with SMA I. Can you email me? GG

This is what we need more of in r/IAmA. We could use fewer celebrities here to shill upcoming movies.

I agree, but maybe we could combine the two and make a movie about 3D printing medical devices! George Clooney could shave his head and play my role in the movie, LOL! Scott Hollister

How much does the process of creating the splint cost? (Not including the actual surgical procedure of placing it in the Bronchus/Trachea).

It depends on whether you are talking about the cost of just making the splint, or all the research, development and regulatory costs that go into it. The cost for materials and machine time would be about $100, if you include R&D and regulatory costs, probably in the low thousands. Thanks for you question. Scott Hollister

Our estimate of total costs with all factors involved is about $40,000. The marginal cost is only $100. We expect this to be very cost effective in the future.

how does this compare to the cost pre-3d printing where you would, i presume, be buying implants from a manufacturer?

This is favorable to conventional manufacturing, especially when customization is considered. The actual costs of medical devices widely varies. GG

Love this!

Got a question though.

In future projects like these, do you still see the cost of R&D being expensive for individuals? I imagine every part has to be designed/tailored to suit that individual and their needs, but of all the R&D costs that went into this particular one, I would hope this isn't something that needs to be repeated with each individual.

Is their a scenario in which you can sort of design a database of blueprints and then sort of tailor them to the individual for a cheaper cost?

Yes, I think (and companies are already doing this) database of CT and MRI scans will be stored to complement a patients own scans. If the patients defect is such that we cannot design a patient part based on symmetry (i.e. like an ear or knee), we can register other patients anatomy and mathematically morph it to fit the patient in need. They we can design and build the implant. I think the R&D costs will come down, but regulatory and legal costs will be difficult to reduce. You are correct though, that with current software we can create an image specific design in an hour or two. Thanks for your question. Scott Hollister

We expect that engineers will play a greater and greater role with patients in the future. This is already occurring with surgical planning for orthopedic surgery cases. The surgeon will sit down with an engineer, decide on the operation and design surgical guides. This is a game changer from the way things were done 10 years ago. GG

How did you verify/validate the designs of your splints to ensure that they would be safe to implant and work as you hoped?

PS: Go Blue!

Verification/Validation involves a number of steps. We first do computer design and modeling of the splint. Then we mechanically test samples to make sure that they have the desired mechanical performance. We have also done a significant amount of biocompatability work on laser sintered PCL as well as testing in pre-clinical models before implanting in humans. Thanks for your question. Go Blue! Scott Hollister

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Without 3D-printing, a customized device with fine architecture would not be possible. Some people have actually tried to make a similar construct with existing bioplastics. They could not put in the microarchitecture and the mechanical properties proved inadequate. The other advantage is the speed in which this was put together. We are able to have a finished product in less than 24 hours.

Actually, the most recent splint had an intricate spiral design that would have been very difficult to make using other processes like injection molding. 3d printing was critical to make this design. Also, because we are making customized devices based on patient anatomy, 3d printing made it possible to modify the design and build it in a day and a half. Thanks for your question. Scott Hollister

How do you feel about the recent 3-D printer story in Grey's Anatomy?

I was going to ask this too!!

Attention for the possibilities 3D-printing opens up helps move the work forward. They should invite us on set as consultants :) GG

How much research did your team do before using this technique on your first patient? What was that process like?

Go blue!

Our own lab has been laser sintering PCL since 2003. We did a significant amount of work building PCL prototypes, studying cell response, and implanting the devices in pre-clinical models with the PCL for other defects like skeletal defects. Glenn and I had designed the splint and built prototypes of the first splint, but had not completely tested it in an animal model before the first patient needed it in 2012. Go Blue! Thanks for your question. Scott Hollister

We might not get to all questions this afternoon (have to get back to clinic/lab), but we'll be jumping back on to answer more later. Keep them coming. Thanks for a great discussion! -Scott and Glenn

How long did it take to print the splints?

Less than 24 hours from the time the CT scan was done. The print run takes about 3-4 hours. GG

What is the method of actually converting the data from a CT scan into a 3d printing blueprint?

The type of file we use for 3D printing is called a .STL file, and is actually a surface representation created by hundreds of thousands if not millions of triangles. We actually do the design all in image format (we move density around in voxels) and then convert the voxels into triangles using an algorithm called marching cubes. One we have the surface .STL file, this data is "sliced" by an algorithm that creates a path for the laser beam or nozzle from the 3D printer to follow. Thanks for your question. Scott Hollister

Wow I was just reading about this here and now I get to ask you guys questions! Reddit is really cool sometimes!

What was the standard treatment for this condition prior to 3d printing? How has 3d printing improved this and are you guys doing any sort of formal evaluation of this compared to the previous standard? I imagine with such an innovative (and apparently very successful) procedure this is the sort of thing you'd like to start spreading to other hospitals as quickly as possible - how is that sort of thing normally done, if say another peds ENT wanted to do this for a patient? Were there any special surgical techniques you had to use for this or is it pretty standard and you're just using a better implant so the learning curve would actually be on the biomedical engineering side?

Also one thing confused me with the way the article was written. Had these babies already had open heart surgery to correct their heart defects by the time they came to you and this operation was essentially to correct the weak airway?

Also how did you guys create the model of the baby's trachea. Do you print another 3d model based on MRIs or something? (edit: article said CT scan. how do you convert that to a 3d printed model???)

Sorry for all the rapid fire questions but this is fascinating to me.

Edit: one last question. What material are the 3d "implants" made of that make them biodegradable and how does this differ from regular 3d printing material. How does cost compare when making a custom 3d printed object vs buying stents/implants etc traditionally? Also how did you guys sterilize it?

edit2: feel free to ignore any of the portions of my post that you already answered. I was typing it before a lot of other answers were posted but it took so long that you've answered a lot of these by now!

There was no effective treatment. Both of these boys were in the intensive care unit, on high-pressure ventilation. They were on high dose intravenous sedation and narcotics. Garrett had been put into a coma and Kaiba had been repeatedly paralyzed to try to keep them alive.
These children died. The FDA trial we are putting together looks at this issue. We will not need many patients to show effectiveness because the results are so dramatic. The airway was corrected concurrent with optimization of the heart defects.
The trachea and splint were created based upon the same CT scan. In fact, the splint was created based upon the virtual airway on CT. Both were printed to help me see how the fit would actually work before performing the operation. The material is polycaprolactone. Sterilized with ethylene oxide. The 3D-printer required a customized patch to allow laser sintering of this. (SH is brilliant).
There are very few FDA approved materials for 3D-printing. This needs to be remedied ASAP. GG

Wow thanks for answering my questions! I am actually a RA who works with a fairly well known Peds ENT in the midwest (I'd rather not post here on reddit) but I am definitely going to be picking his brain about this later and appreciate you clearing things up for me!

What other 3d printing materials have the potential for the most benefits and you really wish the FDA would approve soon?

We need materials with varying bioabsorbability and flexibility profiles. We use sutures of made of many different materials and make devices from many different materials. Similarly, it would be helpful to 3D-print devices from many different materials. GG

Reacted question: I am currently about to begin my undergrad education. I am incredibly interested in what you're doing, and see it as an area of study if love to contribute to. I was planning on studying materials science & engineering. Would you recommend that? Or biomedical engineering?

I advise students to try to find something that 1- they are passionate about 2- they are good at 3- they can make a valuable contribution 4- they can make a living at

Both of the fields are good routes with BME being more straightforward -- choose the one that fits you best.
GG

Our daughter is also treated at U of M and has laryngo/tracheo/broncho malacia. We have enjoyed following your advancements!!! Now that patients have been successfully treated using your techniques what are your future plans with the same technology? What have the downsides of this treatment been? Thank you for the amazing work you do! Go Blue!

We have not seen any complications, but this does require an open chest surgery to place on the bronchi. (The trachea can potentially be treated through the neck).
We are working on a number of different constructs for different medical problems now, including many of the locations bone and cartilage are found. GG

Thank you for the reply! Keep up the great work! I look forward to reading about any further work in the future. Do you think at some point it could be scaled down in the future to not be an open chest procedure? Could the same technology be applied to those older children or adults with secondary tracheo/broncho malacia?

Yes, but the problem set is different for adults. For infants, we needed to accomodate growth but also can allow for strengthening. In adults, full bioresorbability would not work well. We have some solutions we think will work, but they are farther from implementation. GG

Yes, we are working on both of these now. Endoscopic approaches seem very reasonable. We need to modify the technology for older children and adults due to a different set of problems (don't need to worry about growth but needs to be permanent). We think we have the solution, but have more testing to do. GG

Recent neuroscience grad from Michigan, soon to be med student. Just wanted to say keep making us proud. Go Blue!

:)

Thanks for the comment! Go Blue! Scott Hollister

Wow, just, this is amazing stuff. I don't have any words really, but it blows me away the extent of what Doctors can do with advancing technology even over the short span of my 20 years alive.

I'd just like to let you know that you guys and everyone behind the scenes are amazing for what you do!

Thank you very much for the very kind comment. We appreciate your support. We hope to make many more advancements in the technology. Scott Hollister

do you feel supported either in your own institution or by our health care structure at large to advance this technology? what are policy or other barriers that need to be changed?

This is a difficult question to answer. Our institution has definitely helped us get the splint to clinical use. However, I think that there are much greater possibilities that require greater vision. UM could definitely be the leader and the place to go in the US or world, with more support. We have been approached by many people who are interested in pushing this technology forward. I truly believe we are on the cusp of personalized medicine with this technology, as noted in a recent speech by the FDA commissioner and an FDA publication that cited 3D printing of the splint. Thanks for your question. Scott Hollister

Hey Dr.Green! No question - just wanted to say thanks for helping to train me and keep up the strong work! Go Blue - supriti

Hi Supriti! Hope all is going well. Warm regards, GG

If the cost of 3D printing technologies drops sufficiently and becomes more widespread, do you think this would become a viable medical treatment option for third world hospitals, and if so when would we start to see that?

Yes, I think in the future it will be possible to place 3D printers at hospitals, receive designs over the net, and print out the implants right at the hospital. With the cost of 3D printers continually coming down, I believe that such technologies could be in place at third world hospitals in the next 5-10 years. Thanks, for your question Scott Hollister

I expect that it will be very viable wherever customization is desirable. Skilled engineers and physicians will be needed to optimize this. I expect that it will be very important for things like a Martian colony. GG

Did you say martian colony?

3D printers are already being used by NASA in outer space. There are many advantages to having on-site customized manufacturing capabilities with designs that can be communicated from Earth. GG

How big is the hard drive of your 3D printer where you saved these babies?

Also, how much memory does your average baby take up?

The typical size of the splint .STL files varies from 1 to 4-5 MB. Creating 3D models of the individual children may require 100-200 MB. The hard drive of the 3D printer a couple of hundred GBs. Thanks for you question, Scott Hollister

is it exciting that the stuff you are doing is borderline magic?

I had said in an interview, that this was magical to me. It created quite a debate on a board whether or not it was okay to say that something was magical! The idea of turning dust into body parts is mind boggling.
But even more important, we are able to identify solutions to things that had no solution before. Glenn Green

its magic.

you should wear a wizard hat.

practice with me:

Ala Ka ZAM!

Saved a baby.

But seriously, thanks for all of your hard work.

You guys and gals who do this stuff are heroes.

LOL Thanks, GG

I'm looking for a career change and would love to work for a company that can do this. How would this be possible? Thanks for your hard work.

Most is being done at universities now. Companies are more and more thinking about this from a medical device standpoint. GG

Do you think that 3D-printed prostheses will become viable?

Yes, they are already becoming viable. Titanium, PEKK as well as resorbable implants are already being printed. I believe below knee custom prostheses have also already been printed. Thanks for your question. Scott Hollister

They are viable now.
GG

I understand the babies immune systems are very young and that may have some effect on this, but do you expect any immune system retaliation against the splints? Did you have to pre-medicate the children? How did this effect the types of materials you chose when printing the splints, or did you just use "normal" 3d printing materials?

Is there any concern of them developing antibodies/autoimmune disorders in the future from this procedure?

Materials are very important. Polycaprolactone has been used in suture for years, so we are confident of its safety profile. It is fully biocompatable and no immunosuppression is needed. It will resorb in about 3 years and be eliminated from the body, so we don't need to worry about longterm effects.
Regular plastics used in 3D-printing would be rejected by the body. GG

hi doctors!

i believe that my wife may have sent you an image of my son...he has left main-stem bronchomalacia, and she sent you a pic of him in the hospital, with a vest and IPPV being used during his RT. if anyone else reads this, it means that the main left stem of his bronchial tube is floppy - especially on normal exhale, including coughing, this section will close off briefly. the result of this is that, even though he's 5, he's had pneumonia upwards of 20 times, and has been hospitalized about 18 times (he's only 5).

due to the number of times that he's been hospitalized, we have of course asked about options. in the past, surgery has always been out because the risks have far outweighed the possible benefits. however, do you think that this changes that balance at all, or do you feel like this is really a target for more extreme cases than ours?

thank you again, from a very personal place - your work directly impacts families like ours, and it really gives us hope!

Hi. We think that this will become the standard treatment for most children with bronchomalacia or tracheomalacia that requires recurrent or prolonged hospitalization. Right now, compliant with FDA regulations designed to safeguard us all, we can only offer this to children whose lives are at risk. Once we get into a clinical trial, we will be able to offer this to many more children. GG

Do you see Michigan making it out of the sweet sixteen?

Yes!!!! Go Blue! Very tough bracket though. GG

Where do you see this technology headed, say in the next 5 years and 1o years? Will 3D printed organs like Hearts and Livers be available by 2024?

Do you guys read http://3dPrintBoard.com at all?

What are your favorite 3D printing related sites?

Cells are already being printed in hydrogels with nozzle based systems. I think in the next 5-10 years we will see hybrid cells/material systems being printed. Achieving finer resolutions on the tens of micron or micron scale will be another big challenge. Printing organs is a huge challenge, I don't know if we will reach that goal by 2024, it will depend on whether or not we can print vascular systems at the capillary level. Thanks for your question. Scott Hollister

Hey guys! I went to TEDxuofm this past weekend and loved your talk. What were yours thoughts on Professor Stretcher's boiling frog talk? Also when do you think 3D printing will be completely mainstream in the medical field? GO BLUE!

GO BLUE!

I loved the boiling frog talk and even bought his book. That is the type of talk I would wish to give. Thank you for the feedback on our talk -- it should be available online in a month or two.

3D printing is becoming the standard for surgical guides even now, but the process took around a decade. I would expect that it will take around a decade for this to be "completely mainstream."

Thanks for your comments. I also thought the Boiling Frog talk was very moving and inspirational. I agree with Glenn that I wish I had Professor Stretcher's gift for communication. It was a great talk. I think in another 5 years 3D printing will be in the mainstream definitely for surgery. Already people use it for patient models and surgical guides for implants. Our (Glenn and I) as well as others are quickly bringing it mainstream for surgical implants. Thanks for your question. Scott Hollister

I am a student at UM and think your work is so exciting! To change the subject a little, what is you favorite place to eat in Ann Arbor?

My new favorite is Cardomom -- best Indian food I have had anywhere.

GG

Think I heard the story/interviews on NPR a few mornings ago. Thank you for all you do!! My only question is....waffles or pancakes?

I prefer pancakes, but can go either way. Thanks for your comment and question. Scott Hollister

pecan waffles are a weakness of mine. GG

As far as future developments in 3D Printing, what is one procedure that is not possible right now that you would most like to see done?

I think printing a vascular system at the level of capillary beds out of compliant nonlinear elastic materials like real blood vessels would be a quantum leap. Thanks for your question. Scott Hollister

We are working on the answer to that now!!! I think you may hear an answer within a year. GG

I'm probably too late to the thread to catch you, but here goes nothing!

I know this isn't your field of expertise specifically, but can you discuss the applicability of this technology to cardiac repairs?

Our son (16 months) is awaiting his first OHS to attempt to manage an severe aneurysm of his ascending aorta (related to a connective tissue disorder). The primary reason for delaying surgery at this point is the growth limitations associated with aortic root replacement surgery. That puts us in the profoundly distressing position of watching as his aorta dilates progressively towards dissection or rupture (at a complete unknown value in a child so young) as the risks associated with surgery still outweigh the risk of waiting.

Eventually is it conceivable that an artificial aortic root repair could take place with a 3D printed part such as you describe? Also, how functional can this technology be in moving tissues like valves? Our lovely little person also has a bicuspid aortic valve which will likely eventually need replacement too and the cadaver/xenograft options aren't ideal.

Thank you so very much for the work you are doing. Pediatric medicine has become my life since our little person arrived, and I have the utmost respect and gratitude for the people like you who keep him alive.

There are some very exciting changes being made. Customized implants for children with cardiac defects may be the next frontier. Scott Hollister is working with a cardiologist at Michigan and has some very promising projects. But these are still a few years away at best from use. GG

Saw that on the news, nicely done guys. What do you think is next for 3D printing in the industry?

I think that the number of 3D printed, optimized and customized parts in industry will steadily increase as we learn to print more materials with higher quality. Companies like Boeing and Airbus are printing parts for planes. In medicine, 3D printing will help usher in the era of personalized medicine where a scan will be made of your body, a customized implant will be built for you, we will place your cells on the implant and use it to reconstruct a tissue or anatomic defect in your body. Thanks for you question. Scott Hollister

What kind of medical advantages do you think the near future will hold due to 3D printing?

Traditionally, we have surgically jimmied existing devices or have hand-carved body materials (like rib). With 3D-printing, we are able to very quickly make a customized device with precision better than I can hand carve. Glenn Green

Do you Think this could have any uses towards types of Congenital Muscular Dystrophy in any capacity?

Unfortunately, I don't see any near-term use this way. GG

Hi Doctors!! Junior year nursing student here at U of M hospital!! I'm so incredibly excited you are doing this AMA! What was the most difficult setback to overcome in the process of designing this new splint? AND- does the splint being absorbed have any future adverse effects that you are aware of?

Go Blue!

We don't fully know what will happen when the splint resorbs. These children and their parents are very much pioneers. We are keeping a very close eye on them and expect that they will do well without any adverse effects. GG

What's next?

We are in the process of setting up to run a clinical trial for the 3D splint on the road to what we hope will be FDA approval for the device. We also have plans to expand the device to treat other airway problems. In the broad scope of things, we are developing 3D printed scaffold for ear/nose reconstruction, cardiovascular applications, and skeletal reconstruction applications. Thanks for your question. Scott Hollister

how many hours of work did it take you to save those two babies after the software and hardware was setup and ready to work?

an awful lot of hours by many different people. Without the team that we have available here, this would not have been possible. GG

Will it be possible to create artificial meniscus in the knees? Perhaps something that doesn't breakdown or tear?

Yes. There are many labs working on this now. GG

Hello Doctors, I am a sophomore BME undergrad at U of M, stories like this are what interests me in the field. Is there any advice to help me get involved in something like this?

Come talk with us and spend some time in the laboratory. It is one of the advantages to being at U of M -- great students helping us in the lab!

GG

Specifically you guys or just labs in general, because I would love to somehow get involved in the amazing project.

Come see us specifically. But there are many great labs at Michigan. GG

Great pioneering work, well done. INSURANCE INDUSTRY POSITION? - Do you think the relevant insurance business might perhaps be a helpful catalyst IF it were in their interest to hasten the needed changes of laws regarding 3D scaffold and other excellent technologies that are bewildering legislators? - I thought of them because they are 'big' players - the stakes may be high for them, so perhaps they'd consider investing. There may also be 3D printing industry interests, and other parties like Singularity University, who'd collaborate. Bruce Thomson in New Zealand.

The potential for costs savings with 3D printing is potentially very helpful for getting insurance coverage. But coverage is a separate issue from FDA approval. The potential for coverage is necessary for viability of most medical products (cosmetic devices and dentistry being notable exceptions). GG

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Yes. NASA is doing this now. This article in the NY Times talks about both. http://www.nytimes.com/2013/05/28/science/3-d-help-for-breathing-vanishing-amphibians-and-more.html?_r=0 GG

Can 3D printers be used to create joint or bone replacements? What kind of rejection possibilities do you face when you're putting these things into people? What are they made out of??? I have zero knowledge of 3D printers but as a person who has had bone grafts I think this emerging technology is incredible. Thanks!

We think that this may largely replace bone grafts in the future. The splints are made of polycaprolactone. When they are impregnated with stem cells, we have successfully created cartilage.
GEG

Yes, in fact my own lab does quite a bit of work designing and printing bone replacements. We printed a scaffold for jaw reconstruction with a colleague at the University of Michigan dental school that was implanted in a patient in Milan Italy who is now 6 months post surgery and doing well. We (my lab along with Dr. Green and some other colleagues) hope to expand this application in the future. Right now we are making these replacements out of PCL. Thanks for your question. Scott Hollister

Hi! I'll be an incoming freshman at the University of Michigan in the fall; what is your recommendation on how I, a freshman undergraduate student, can get involved in this type of research?

Come talk with us. One of the great things about being at U of M is great students.

GG

Hi, I'm studying molecular bio and genetics in University of Toronto and I take a bit of social sci courses on the side. I'd just like to get your perspective on something:

What if the printed organs were designed/coded to be waaaaaay better and more efficient than normal human counterparts and laws didn't prohibit a person from getting transplants just because they want to. Lets say that a kid was transplanted with a better heart and respiratory system because his parents wanted him to become an athlete. He could exercise better and train better because he had enhanced organs then he ends up getting a gold medals in several olympic events. Personally, do you think this would be an unfair advantage? Would this give way to "designer" humans? (by designer, I mean artificially designed humans due to enhanced organ transplants)

Most athletes now have an unfair advantage based on the genes they inherited from their parents. I think that individuals with medical implants will have to be closely examined for the fairness of competition. Oscar Pistorius directly raised these issues. I think we may very well see more concerns going forward. The large tracheal resections I perform theoretically give someone a huge athletic advantage by removing deadspace, but so far none of my patients has been exceptional. Success in athletics relies on so much more than inate ability. GG GG

Hello Doctors,

I'm an undergraduate at the university with a comp sci focus. I was wondering if you felt as though the software you use for the purposes of storing patient data and information was sufficient or lacking? Not only speaking about the EHR system, but also any other data software you use? Could you tell me what Software you use on a daily basis?

Thanks and congratulations on the successful surgeries!

Thanks, I think currently computing power for dealing with very large datasets (i.e. whole human body scans) but ranging across many physical scales (i.e. millimeters or microns to centimeters) is still lacking. We use multiscale methods like homogenization theory to deal with this, but putting it all together for manufacturing remains a challenge. Thanks for you question. Scott Hollister

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Thank you. In many ways, we don't know all of the possible side effects. These children and their families are pioneers. We believe that there will not be side effects based upon the experience with the materials that we have used and what we have seen in animals. But there is no true animal model for this life-threatening disease.

Thanks, I am glad you used this for your presentation. Whenever you implant a material in the body, especially a biodegradable one, there are potential side effects, for the degradation products,etc. Polycaprolactone (PCL) the material we use, has been widely studies for implants and is very biocompatible. Issues may relate to the mechanical stiffness of the device, and how well it accommodates tracheal growth. We are studying this in a pre-clinical model right now. Thanks for the question. Scott Hollister

Hey Dr. Green and Dr. Hollister,

What do you think are the future medical uses of 3D printing? Will full organs be an option in the future(no matter how far) eliminating the organ donor waiting lists? What do you think is the farthest this technology can go, given the the evidence currently available? It can be something conceivable or even "sci-fi" in nature. Also Dr. Hollister, that is a sweet soul-patch, keep on rocking it.

Thanks for your work, you are on the forefront of the future.

The immediate use is for constructs that are relatively inert: bone and cartilage. Mobile constructs are in the works: muscles. Neurologic and sensory constructs are probably the last (eyes, ears) Brain tissue will likely be the last. GG

What are the current limitations with this procedure/process and how are they being addressed?

Do you plan future collaborations in this field or was this a one time thing?

Current limitations include the range of biomaterials we can print with and the resolution of the printer. We are researching how to process different materials for 3D printers. We do plan many more future collaborations and different applications using this technology. Thanks for your question. Scott Hollister

Have you gotten any negative feedback or criticism as a result of these groundbreaking efforts?

Not really. GG

How important do you see biomedical engineers in the future? I'm studying biomedical electrical engineering, and am in constant fear that I won't know what to do with my degree upon graduation!

I think that with increasing healthcare needs and the desire to push global health in the developing world, there will be a greater need for biomedical engineers. The difficulty is that biomedical engineering is a very non-traditional engineering field, and it is difficult to go the traditional route and get a job with a Bachelors. A post-graduate degree is typically required. But hang in there! I think it has a bright future.

Scott Hollister

I think they will become increasingly important. There are so many options available to BME with EE background, I think you will have many options. Choose what you feel passionate about!

GG

• Do you model the pieces visually after seeing the CT scan using Rhino or a similar program? Is there a program specifically for medical use in the 3D printing realm?

• Do you think this technology will lengthen human life-span (printing new organs)?

• If yes, is that responsible given our overpopulation issues?

We use a combination of custom written MATLAB programs and image-based design programs to design the splint along with Mimics by Materialise to create the .stl model of the patient. We then import the stl rendition of the image-based design into Mimics to fit the design to the anatomy. I think it can extend human life. Regarding this, I believe that when you see your loved ones suffering, you definitely want to do what you can to ease their suffering and improve their life. Thanks for your question. Scott Hollister

Do you believe 3-D printing could be used for other anatomical birth defects, and specifically for EA/TEF kids? My daughter had type C long gap (tracheamalacia, also, though it has improved over time) and did not respond to the traditional esophagus stretching technique for a primary repair. She had a successful gastric interposition surgery to connect her esophagus and stomach right before her second birthday. When it was determined that the esophagus stretching did not work for her while in the NICU, her surgeon gave her a spit fistula to allow her to swallow comfortably and lead a "normal" life at home until she was ready for the big surgery. So, for kids like her, could a 3-D esophagus splint be a future possibility to have repair sooner or even as an alternative option to moving internal organs?

And thank you for the work you do! I have been honored to have a cutting edge surgical team following my daughter's complex case (her surgical team performed the stem-cell created trachea transplant on a 3 year old last year), and can I tell you that the work you do gives many families hope and comfort when caring for their children! Thank you!

We are expecting to use the splint for many children with tracheomalacia related to EA/TEF. We think that printed materials may very well take over many of the areas where grafts and flaps are used now. GG

Hello Doctors! I'm a PhD student working on 3D printing of tissue as well! In the biomedical sphere, we tend to design experiments that are (intended to) meant to help people, or address an ineffective treatment method. How do you move from the academic research side of things to a position in which your idea is affecting real lives? I/my lab already have a few patents that I think could make a difference, but we aren't sure where do go from here. Thank you for your time!

Connecting with a collaborative team is very important. Please send us some more information. Feel free to email me. You can find my email address in our New England Journal of Medicine paper. GG

What prevents the body from growing scar tissue over the split? Would a permanent repair be to allow the scaffolding to attach to the bronchi or trachea and tissue to fill in the area to make the trachea stronger less susceptible to collapse? Our daughters heart patch we have been told the body fills it in and essentially fills over the patch with scar tissue. Could this same premise be used here on the outside of the airway (obviously adding the lumen of the bronchi would be problematic if scar tissue filled it in).

The body can grow scar over the splint and does, just as scar forms in any area of the body. The key is that the material is biocompatible and does not cause excessive reaction. This is designed to be a permanent solution. The splint opens with growth and dissolves once the airway has grown with enough strength to avoid collapse. Due to the Bernouilli principle, the collapsing pressure decreases as the size of the airway grows.

The micromechanical properties behind the splint were very brilliantly designed by Dr. Hollister. GG

Will the printed parts have to be removed and replaced as they grow? Or how long will the splint stay in if the babies can be naturally healed?

The splint dissolves after about 3 years. Scott engineered the splints to open from the inside to allow airway growth. It has been very satisfying to see this happen for Kaiba. GG

After the first successful splint were there variations in the design? Did any variations actually change the effectiveness or efficiency?

I heard the story in NPR the other day, truly fascinating. I love seeing technology change they way we look at the world and the medical field especially.

We made some variations in the design to accommodate the patients specific anatomy, which is really the beauty of image-based patient specific design combined with biomaterial 3D printing. We were able to make these design changes and build new splint devices in about a day and a half. We believe that the changes in design allowed us to put in two splints to address this patients need. Thanks for your insightful question. Scott Hollister

There were size and length differences based on anatomy. But more importantly, because this was bilateral, the splints would have hit each other near the carina. Scott designed a spiraled splint to avoid this contact. It was a little trickier to place surgically, but worked very well. GG

With medical expenses in America being what they are, are either of you concerned about how expensive treatments akin to this might become? Say creating artificial components? I am concerned that items like these could have their designs patented, and their expenses skyrocket. Any thoughts on this? Is this scenario easily avoidable?

I think this is an area where the costs could be driven down over time. Medicolegal risk exposure (i.e. threat of a lawsuit), regulatory costs will keep the costs relatively high even if the production cost is low. Patents involved with 3D printing are expiring soon which will further be able to drive the cost down.

For the splint, we estimate a cost savings of about $1 million in comparison to the costs of keeping a child in the intensive care unit. In Garrett's case, he has required hospitalized care for his entire 18 months, but will be going home for the first time in his life within a month.

GG

Have you seen anything about using a 3D printer in terms of stem cell research? My brother is type 1 diabetic and we've heard that using pancreatic cells might be the key to a cure. Does this seem possible?

Yes, it seems possible. We have nonembryonic stem cells that we are using with 3D constructs right now. There are much bigger difficulties in translating these breakthroughs to human use. GG

What is the biggest drawback to using this type of procedure? Go Blue!

I would say the biggest difficulty is adapting the material to use with the 3D printer. The biggest drawback is our inability right now to print with all the biomaterials that are currently available. Thanks for your questions and GO BLUE! Scott Hollister

Go Blue!

The biggest drawback is that it is not FDA approved yet. The other drawback is that it requires an open thoracotomy at present. GG

I read the splint was constructed out of a biopolymer. PLA is a biopolymer but I assume it's something else that's done on a SLA machine? Is this something being developed?

There was a TED talk about a guy who modeled and 3d printed a stint for his heart so we wouldn't have to take a blood thinner for the rest of his life. Would 3d printing the biopolymer stint work the same way for hearts?

We use polycaprolactone (PCL).

I don't know the details of 3D-printing a stent for the heart. What has been done is to make a model of the heart with a 3D-printer and use the model to design/mock up surgery. (This made the news recently as a 3D-printed heart, even though the heart was a nonfunctional model used to visualize the operation more readily.) This is much different than manufacturing the surgical implant.

GG

I use 3D-printers on a regular basis for surgical design.

GG

Do you sell these 3d printers?

We don't sell these printers, we use a commercial (EOS) system that we adapted to build with a biomaterial.

Thanks, Scott Hollister

You can get 3d printers all over the place and even buy kits to make your own at home. I imagine the tricky part is having a CT scanner and the knowledge of how to use them together!

Yes, that is true to some degree. Adapting the biomaterial to work with the 3D printer is very difficult, as well as the 3D image-based design approach that we developed. Thanks for you comment Scott Hollister

Scott has a customized software patch to the machine to make it work for polycaprolactone.
Mimics software has made integrating CT scanners much better. What takes the most amount of time now Scott? GG

According to the signs in your photos, one of you is on daylight time and the other is on standard time! Will learning to tell time help the Wolverines beat the Buckeyes?

Seriously though, this is absolutely amazing work, gentlemen. I feel lucky to live in such an amazing time and humbled that you would take the time out to talk to us.

My bad, I still haven't adjusted to daylight savings.

Good thing the Wolverines don't need me for March Madness.

GG

Would you guys allow us to "Hi-5" you in the hallways?

Please do! GG

I'm here at U-M and stories like this make me really proud.

I'm wondering if you could talk about the interdisciplinarity that I assume is inherent in biomedical engineering and solutions like this one.

I see 3-D printing, digital modeling, computational geometry, toolpath programming, and so on happening in a ton of different fields (and all across our campus here). But a lot of the people with the skillsets to aptly deploy digital technologies for custom manufacturing would lack your critical knowledge of medicine. What are the backgrounds of the people on your team? How have you made connections to advance this work?

The team has a wide variety of backgrounds, many with both engineering and medical backgrounds. Kyle was a 4.0 BME undergrad at U of M before medical school and is now a surgical resident who works in Scott's laboratory. The University of Michigan is particularly good at collaborations. Scott Hollister's willingness to work on a tough clinical problem with me is what made this even possible. GG

Was the situation of making the splint very intense? What kind of window did you have to work with?

It was very intense. We actually failed to make it through the regulatory process in a previous attempt to have a splint ready for a child that needed it :( We have the process much more streamlined now. The manufacturing has always been quick and suitable for these life-threatening cases. GG

I heard about your work on NPR the other day. Fantastic job! Hopefully successes like this make it faster and easier to develop 3D printed medical devices on a case by case basis.

From what I understood, dealing with the FDA was something that really slowed down the process. What can be done to establish faster throughput? QA/QC, approved materials etc...?

The FDA has been very helpful and supportive. There are many individuals working very hard at developing strategies for 3D-printing going forward. Trying to keep people safe and encourage improvements is not easy! GG

Our experience with the FDA has actually been very positive. They have been supportive of us taking this approach. In fact, if you Google "personalized medicine FDA" you will see the splint on the cover of one of their reports. Obviously, regarding quality systems, there is a lot of work and study to be done to validate 3D printing processes. Especially verifying the geometry that may be built with these processes, and how these design parameters affect clinical outcomes. Thank you for your very thoughtful question.

Scott Hollister

• What 3D design software do you use?

• Did you two design and print the splints yourselves using the software?

• Kind of a random question, but when performing surgery on infants what kind of precautions have to be taken into account by the surgeon?

Mimics software and MATLAB. Software patches were also applied to the 3D-printing machine.

We developed the design configuration together. Scott then computer-designed and printed the splints to the CT scan in his laboratory with his biomedical engineering team.

GG

What are the implications for self medicating with 3D printers? (in your personal opinions, of course)

3D printers allow for manufacturing in environments that would not otherwise tolerate it: isolated island populations, south pole, even a martian colony. This will be very nice for doctors in very remote areas now.

You are right that it does allow people to make more complex devices for themselves. Surgically implanting them requires a greater skillset but there have always been rogues.

If you are implanting a device into yourself that you manufactured yourself with a 3D printer ......

you are probably in an awesome game.

GG

-How did you account for patients growth with age making sure the bronchi are not constricted by the stent? -It looks like your stent goes around the outside of the bronchi. What adheres the bronchi to the stent scaffold so healing can take place in the correct shape?

Sutures suspend the trachea to the scaffold. The splint is designed to open with growth and then eventually dissolve. We match the splint size to the size of the patient based upon the CT scan. (The splint is directly made to the CT scan by Scott.) This has worked very well in rapidly growing piglets. It has also been working for Kaiba, the first recipient, whose splinted bronchus has actually grown faster than the unsplinted side. GG

Dr Hollister: What are you storing in that poor skull's eye socket? (In your "proof" photo)

Actually, I had a sponge of a different material on a table in my office and my kids were visiting the office one day and stuck the sponge in as an 'eyeball'! LOL. Thanks for the question. Scott Hollister

Hi, I am a high school senior looking to go into materials science in college next year and am taking a high school level course on nanotechnology and another where we use a 3d printer. I am wondering what will happen to the splints when the babies grow? will they need a new one or by that time will the body have healed the airways?

The splints open as the airway grows and then dissolve. During this process, the airway becomes stronger and larger, eliminating the malacia. We believe that this will be sufficient for a lifelong cure. GG

Our hypothesis is that the trachea will remodel and grow with a normal cartilage ring architecture as the splint resorbs over a period of 2 to 2.5 years. The splint does mechanically expand to allow tracheal growth. We believe that once the splint resorbs the child will be fine from then on. Thanks for your question. Scott Hollister

Hey guys! This is some awesome stuff. Did you use a normal off-the-shelf 3D printer? I know the material is different but I'm curious if a normal printer would be able to do this.

Thanks, and Go Blue!

Not an off-the-shelf 3D printer. Scott custom patched a high end printer. GG

Have you guys ever said, "fuck it" and printed something crazy for fun? What was it?

We printed a brain. GG