Treating Type I Diabetes with FRESH Bioprinting: Interview with Mike Graffeo

Discover FRESH 3D bioprinting with Mike Graffio, CEO and co-founder of Fluoform3D. Having met at Carnegie Mellon University, Mike and Adam Feinberg have been on a mission to revolutionize the field of bioprinting, focusing on creating replacement tissues and organs without introducing foreign substances into the body. Mike shares the captivating journey from their engineering days in the 1990s through a pivotal 2015 conversation that transformed their research into a thriving startup and onto achieving significant milestones like developing living cardiac tissues and heart valves by 2018.

Our conversation uncovers the next frontier in 3D bioprinting, particularly the promising strides in islet cell replacement therapy for diabetes. You'll hear about how the FRESH bioprinitng propels this innovative field forward. With breakthroughs in small animal models showing potential for diabetes management, we explore how the team is gearing up for more extensive studies and human clinical trials. This episode also delves into their strategic fundraising efforts and partnerships to bring these advancements to life.

Summary:

• Overview of Fluoform3D and its founding story 
• Explanation of FRESH Technology and its significance in bioprinting 
• Current progress in cardiac applications and in vitro tissues 
• Ongoing projects related to therapeutic applications  for type I diabetes
• Insights into navigating funding and building investor relationships 
• Discussion on regulatory pathways and interactions with the FDA 
• Emphasis on company culture and team dynamics 
• Recommendations for industry insights and staying informed about bioprinting trends

Show Notes:

Instagram interview with Mike in 2021
Fluidform3D website
Breakthrough publication in 2019 made it to the cover of Science magazine-"FRESH 3D Printing Used to Rebuild Functional Components of the Human Heart"
YouTube Video: https://youtu.be/BJbReV0v7Co

 

Chapters

• 0:01 Fluidform3D Founding Journey
• 13:21 FRESH 3D Bioprinting Technology Overview
• 26:11 Building Effective Teams in Biotech
• 35:22 Leadership, Bioprinting, and Stoicism

Transcript

Jenny Chen: 0:01

Today I had the pleasure of interviewing Mike Graffio, ceo and co-founder of Fluoform3D, a 3D bioprinting startup out of Carnegie Mellon University focusing on key applications using fresh technology also known as freeform reversible embedding of suspended hydrogels. I have always been impressed with how Mike and his team navigate the challenging task of commercializing life-changing tissue engineering deep tech, and I hope this conversation can serve to guide and motivate more scientists and entrepreneurs in this space. Enjoy, all right, I think we are started. Hey Mike, hey Jenny, I can't believe you're in my office.

Mike Graffeo: 0:47

It's so good to be here.

Jenny Chen: 0:48

Thank you for having me. I think we met like what 2018?

Mike Graffeo: 0:54

Yeah, late 18, early 19, something like that.

Jenny Chen: 0:56

Yeah, so time flies.

Mike Graffeo: 0:59

It's hard to believe it's been almost six years.

Jenny Chen: 1:01

Most marriages already ended by now and you're still the ceo of flipform 3d, which is incredible, because I know it's an adventure for you and, uh, I think why don't we just start with that? That you're. I know we did a. We did an interview with mike a couple years back and at that time you actually had a giant speaker, a beaker with a big heart printed in the beaker. So, yeah, if people were interested, we can include a link in the notes to see what that does look like. But why don't you share with us your founding story?

Mike Graffeo: 1:39

Sure, yeah. So the story actually starts a long time ago my co-founder, adam Feinberg, at Carnegie Mellon. He and I have known each other since the 90s. We were co-op engineers together as undergraduates and we both sort of fell in love with this idea of how do we use engineering to solve problems around the need for replacement tissue organs, things like that and it led us both down a path that we've kind of been on ever since. I spent my career commercializing new technologies in the life sciences devices, combination drug device products, therapeutics and Adam went off to do his PhD, do his postdoc at Harvard and then has been at Carnegie Mellon ever since.

Mike Graffeo: 2:29

At Carnegie Mellon they spent a good deal of time in the early teens looking at the field around 3D bioprinting and asking the question what's it going to take to make this translationally relevant? How are we going to make 3D bioprinting into something that we could actually build, something that could treat a condition inside of a human? And they came to the conclusion that they needed to develop a new way of thinking about bioprinting. What they needed to do was figure out how to do bioprinting without introducing chemistries that don't exist inside the body. So you know a lot of work went into developing what became Fresh 3D bioprinting and in 2018, you know they were ready to start thinking about how do we turn this into a company, how do we start doing this work at scale? Adam and I had been in touch, so I met with him, met with the postdocs and PhDs in his lab who became my co-founders, and we spent a good deal of time putting together a plan and putting together how we thought it made sense to build out a business, and we incorporated the company in 18. We started working on first getting a license from Carnegie Mellon and then raising money and getting things off the ground, and that was really how it started.

Jenny Chen: 3:43

Do you still remember the first conversation you had with Adam, when he first said hey, mike, I got an idea for a company? Or did you approach him to say, hey, I think what you're working on is worth. You know a company as a commercialization idea.

Mike Graffeo: 3:57

Yeah, so there were two conversations. I remember them both pretty well. In 2015, I think it was, there was a publication out of their lab in Science Advances, and Carnegie Mellon did a lot of PR around it, and it was sort of the first evidence that this new bioprinting technology Fresh actually worked. And so I had reached out and I simply said listen, this is the coolest thing that I've ever read about. You know, remember that if you're ever thinking about trying to start a company or whatnot, you know, don't forget you've got friends in industry like I'd be happy to help. And he wrote back and you know this is very Adam about this. He wrote back and said listen, you know, appreciate it, excited about it. The technology is going to be great, but it's not ready for prime time yet.

Mike Graffeo: 4:43

We've got to do more work first, and it's a great, you know, you let me know whenever it makes sense In late 17,. I was thinking about that conversation. I don't know why, but it just sort of popped into my head and I had been having the thought process of whether I wanted to keep working in, you know, larger companies. At that time I was with a mid-cap publicly traded company, Insulate Corporation, where I led business development, and I was really missing my time at startups. I'd spent six years in startups prior and I was starting to think about whether there was something that made sense to do. So I reached back out to Adam and I said you know, hey, I remember it wasn't quite ready for prime time, Would love to get an update. And he replied pretty quickly and said how fast can you get out to Pittsburgh? I've got something I'd really like to show you, Nice.

Mike Graffeo: 5:35

And so what I saw? I was out in Pittsburgh in I think it was January of 18. And that was when you know, this was before the paper that came out in science in 2019. That was when we saw. I saw for the first time the work that my co-founders have been doing building was when we saw. I saw for the first time the work that my co-founders have been doing building, you know, living beating cardiac tissue that was recreating complex arrhythmias, and the ability to build heart balance out of collagen, and all of the work that ultimately became this, you know, the most cited paper in all of bioprinting.

Jenny Chen: 5:57

I get to see all of that a year and a half before the rest of the world did I do agree that 2018 and 2019 are the most exciting years, at least for bioprinting, because I remember your paper got published and I remember Volumetric paper got published as well, both on the cover of Science Magazine within months or whatever, which is quite exciting. You know, we really thought we're going to have a beating heart that's going to be completely bioprinted.

Mike Graffeo: 6:23

back then, I mean it's still going to happen right.

Jenny Chen: 6:25

So what's going on with the heart project for now?

Mike Graffeo: 6:28

So there's been some really exciting developments in the cardiac space, including some work that we did at the company building in vitro cardiac tissue. We're able to demonstrate that we can build tissue in the lab that can pick up signals in the process of drug discovery that really can't be picked up in existing assays.

Mike Graffeo: 6:46

That's been really cool. We've got a uh, we've got one commercial partner with that that is seeing some really great results. So what we we really like the the, the signal that we've gotten out of the work that we've done in cardiac that we can build highly differentiated relevant tissue in vitro. But what's much more exciting, I think, is the work that's being done in vivo and you know now we can sort of talk about it because Adam and team have finally presented on it. But there's been a consortium of researchers using our technology to develop a pulsatile heart conduit for a congenital heart disorder called single ventricle disease and they've made enormous progress and they've actually seen extended in vivo results that are really really compelling. So basically, think about picking up the function of the right ventricle and pulsing blood, pumping blood out to the pulmonary system, and this is just published.

Jenny Chen: 7:48

So this is not even yet published, but just presented for the first time, just about a month or two ago. If there's any link, just share with us and I will add to the notes and share what we said yeah, happy to.

Jenny Chen: 8:00

Now I think it will be lopsided to talk about other applications without going back to the fundamentals, which is what is fresh technology. I think I have a pretty good idea. I mean, we all have a good idea. But for people who don't know what it is, do you mind if we just kind of verbalize what it is?

Mike Graffeo: 8:17

Absolutely so. You know, the idea that came about and became the technology the company's founded upon was the notion that, if you take most of 3D bioprinting, the core problem that needed solving was biology cells, proteins. They don't behave like plastic when we deposit them, they don't stay where we put them.

Jenny Chen: 8:40

Right.

Mike Graffeo: 8:40

And so most of the field has spent a lot of time working on how do we modify the inks, how do we change the chemistry, how do we very rapidly fix those things? And it's really limited the materials we can work with and it's made it so that you know it's made some very cell unfriendly environments. It's made it very challenging to do bioprinting in the way that we'd really like to. We'd really like to.

Mike Graffeo: 9:08

So my co-founders spent the time to figure out hey, what if we, instead of 3D bioprinting by depositing materials in open air, what if we immobilize those materials inside of a gel? And by doing that and the work that it took to figure out what kind of gel would work and making it a yield stress material, so the gel would be self-healing but it could release at a body temperature. So it was all still sort of physiologically friendly. What really became interesting was there were three core benefits of doing this sort of inside of a gel printing Benefit. One was we could immobilize those materials so they could stay in place long enough to go through the native self-assembly processes that all of biology has access to. It just takes longer than cooling a plastic down.

Jenny Chen: 9:49

Yeah.

Mike Graffeo: 9:50

Number two is you know, we build those gels out of a series of tiny little gelatin microparticles. And so we can incorporate the microparticles into the filaments that are printed.

Mike Graffeo: 10:00

And that allows us to control a level of surface porosity in what we print that can't really be recreated any other way. It allows us a level of resolution that's much, much smaller than the filaments that we print. So I describe to people think about, like the dimples on the surface of a golf ball. We can sort of tune how much dimple or not we get that patterning. That porosity that we can build allows us to control how much cellular and vascular infiltration happens when we implant these things in the body, and so that's a level of control that's really, really exciting.

Mike Graffeo: 10:34

And then the third thing is we're able to build inside of an environment that outside of those microparticles is basically aqueous. So we now have a direct chemical interface with what we're building. It allows us to take advantage of not just pH-driven gelation mechanisms but enzymatic and ionic-driven mechanisms. So we have a level of chemical control that means we can print with a much broader palette of biomaterials, and we can do it all leveraging the native self-assembly mechanism. Now the thing that is, I think, the most powerful about this technology I could talk about this technology all day.

Jenny Chen: 11:11

I'm inviting you over.

Mike Graffeo: 11:12

I appreciate it. Yeah, the thing that I'm most excited about and that I think is really transformative in this space is it allows, it serves as a really, really powerful vascularization plaque. So we have seen data the first data was published in Science in 2019, where we showed, you know, taking a small disc of collagen and implanting that subcutaneously in the mouse when you cast it, versus fresh print it with exactly the same materials. Otherwise, the casted material sees no vascularization in vivo whatsoever. The fresh printed material sees extensive vascularization and that's really driven by that sort of porosity effect that we talked about, but also the native sort of chemical self-assembly that happens. So that becomes really exciting because vascularization has been the biggest challenge in all of tissue engineering, writ large not just in bioprinting but everywhere. So that's been sort of the core unlock for what became our lead program now.

Jenny Chen: 12:14

Do you remember NASA had a vascular challenge program that award a million dollars.

Mike Graffeo: 12:20

I do.

Jenny Chen: 12:21

Were you young enough to remember that, because I know that's many years ago.

Mike Graffeo: 12:24

I was out at NASA Ames for one of the big meetings that they had. I remember it well. In fact, I we I do really believe that the vascularization data that we have now has far surpassed what was shown for that yes, and is a lot more clinically relevant. So it's actually instead of sort of solving for how do we win the NASA challenge. The team at Carnegie Mellon kept their heads down and said how do we win the? Let's make something that can actually be implanted in the body.

Jenny Chen: 13:00

Absolutely. I have you know I'm not really following the masterization aspect closely in the last couple of years, but I can tell a lot of hard work has been put in that's not totally publicized. Now, speaking of publicized fresh technologies, you and I probably on LinkedIn a lot and you can see a lot of videos that looks just like fresh print videos. People are printing all kinds of stuff. How do you differentiate that? Because you know, are they using your technology or are they having their own different kind of fresh technology? How should I approach these news or share or publications?

Mike Graffeo: 13:43

It's a great question At its core. In the United States we live in a first-to-file IP environment and the team at Carnegie Mellon was the first to file. There were a few other groups that had done some very similar work and we're fortunate to be the ones to whom the patent was issued. So we have the foundational IP on all of the embedded printing inside of a gel type approaches. So if you see anything that looks like 3D printing embedded inside of a gel that'll be released later on, that's effectively our IP.

Mike Graffeo: 14:19

Now there's a lot of groups in academia that are doing that. We love it. We think it's fantastic. It does nothing but sort of promote that. This is the most widely adopted and the most powerful and useful 3D bioprinting technique in the world. The world and at some point, as those applications that researchers are developing elsewhere you know, intend to move out of the lab and into commercialization, we look forward to working with them to either facilitate us taking that in or them taking a license out to fresh and making that available. I think there's far more applications than any one company can develop themselves here, given the power of the platform.

Jenny Chen: 14:54

And you guys have the exclusive license rights to the license we do. Okay, that's fantastic. Now San Francisco and Boston are expensive cities to travel to and you're not here to see me. Obviously, you're here for the JP Morgan Conference, and why don't you tell us what kind of news you brought to the conference and what are some of the agenda on your schedule, your calendar, next couple days? You know what are you looking forward to yeah.

Mike Graffeo: 15:23

so you know it starts about well about a year and a half ago, where there was some data that came out of the lab at Carnegie Mellon and Adams lab that really showed some compelling reasons to believe that we could build our first therapeutic application. They had done a ton of work with the organization that at the time was known as JDRF it's now known as Breakthrough T1D and that had been focused on the idea that in islet cell replacement therapy, one of the big challenges is how do we get enough blood supply to the islets that we transplant. And so when they saw the data out of the science paper, they said listen, is there any way that we could work together to identify how can we help better vascularize islets using your technology? Based on the data that they saw, we spun up a therapeutic program inside of fluid form. That's now our biggest area of focus, and so for the last year we've been developing all of the small animal data demonstrating that we can build using our fresh printing technology. We can build an implant that has islet cells, that has ECM proteins, that is able to be implanted subcutaneously, that vizes rapidly and that demonstrates function.

Mike Graffeo: 16:35

So the data that we're here to promote we're really excited about is our now it's almost four months data where we take a diabetes model of a mouse. Take a mouse, we induce diabetes, we see blood sugar levels go up really substantially, really quickly, and then we do our implant and we see those blood sugar levels come back down to normal and stay there now out for several months. So we've seen data that we're really excited about and we are basically taking that now out to the next level to move out of the small animal models into the large animal models that will be required to go to the FDA for, ultimately, a human trial. So we're out here to share those data. We're actually actively, you know, raising our series A, and so the course of the next several days we've got meetings with investors, with strategic partners, some company presentations, and really focused on making sure that we've got the ability to go and do these large animal studies.

Jenny Chen: 17:30

And you allow me to tell people how much you're raising.

Mike Graffeo: 17:33

Of course, yeah, okay.

Jenny Chen: 17:34

So yeah, studies, and you allow me to tell people how much you're raising, of course, yeah, okay. So yeah, if, guys, you have $25 million time to write to Mike, that's the best type of fundraising Just one check and done with it.

Mike Graffeo: 17:44

Well, you know, as fundraising is never an easy process and it's about finding, you know, both the capital that you need, but it's also about finding the kind of partnership that you need for a long haul. These are these are really significant endeavors, right To get to the stage of doing human clinicals and then to take it out to the market and ultimately try to cure disease for a lot of patients. So what you're looking for is a like-minded group of people who believe in the mission, believe in the value and really want to help in any way that they can.

Jenny Chen: 18:10

Now your ideal profile of investor. Would this be a corporate VC from a large company, a pharma company, or it could be just any kind of traditional VC? What is your ideal profile at the moment?

Mike Graffeo: 18:31

So it's a good question. So it's a good question. The way I think about it is there's really three categories of investor type four categories of investor types who have active interest in this kind of space.

Jenny Chen: 18:42

Yeah.

Mike Graffeo: 18:43

You described. There's the corporate VCs who have an interest in type one in general, so that's one discrete category. There's the classic biotech VCs that also make sense. There's what I would call the sort of biology adjacent tech VCs and then, last but not least, there are, you know, family offices and individuals who, where diabetes has been a big part of their life and it's an important area to them. For us, you know, I wouldn't say we have a preference of one over the other or an ideal. What we're really focused on is finding the right people who share our vision that a subcutaneous treatment that is minimally invasive, is easily retrievable and is highly engrafted, so it's viable and it's durable, that that's the thing that actually opens up treatment to the millions of people with type 1 around the world. So for us, that's the real credit, it's that like-mindedness around the mission, because I think listen, it's a startup, every startup hits difficult days and you know that that shared mission matters when you're trying to solve problems like that.

Jenny Chen: 19:48

Yeah, well, now going back to this other new technology that you guys have, we actually chatted a little bit before this podcast that there are a couple competitors out there, potentially and when, in fact, probably already commercializing. Would you like to elaborate on this a little bit so we have a general understanding what the space is like?

Mike Graffeo: 20:07

of course, yeah. So you know, in this space today there are, I would say, a few different approaches that go back, some as far back as 30 years ago. So there's a commercial product that was approved by the FDA about a year ago by a company called Cell Trans, the Lantedra product, and that's a human cadaver donor islets that are infused into the portal vein and patients who get that therapy, they need to be on systemic immune suppression for the rest of their life.

Mike Graffeo: 20:37

It's a great option for patients who have very, very poorly controlled diabetes or maybe patients who are already on immune suppression for another reason. The majority of people with type 1 would not make the trade to say, listen, I'll give up my immunity for the ability to no longer have to take insulin shots. So that, as a treatment, is a big step in the right direction, but it's not enough. There's other groups out there. Vertex made a very big splash in the space a few years ago buying sematherapeutics, and they're definitely the most advanced of kind of the next gen of therapies. They've got a terrific portfolio of ip around the induced pluripotent stem cells and you know getting those to behave uh, in an islet like fashion, and so now they're in the clinic in what was just announced that they had done a phase one, two and they've now converted that into a phase one, two, three with another cohort, and so this is a really exciting development because, unlike the Lantigera product, that product will be stem cell derived, so there's no limitation on the sourcing of it.

Mike Graffeo: 21:45

There's no you know there's no only you can only treat so many patients. It'll be a much more kind of broadly available treatment, but that still requires systemic immune suppression, more kind of broadly available treatment, but that still requires systemic immune suppression. Then there's a couple of categories of programs behind that, including the programs that are centered around what I'll kind of call broadly, you know, a encapsulation-based approach.

Jenny Chen: 22:09

I definitely have seen that before. One of them is actually in the Bay Area. I forgot the name.

Mike Graffeo: 22:13

Yeah, so there's a few different people have been working on encapsulation for 20, 25 years now. Uh, going back to the original islet cell transplant work where they realized, boy, if we can't protect this from the immune system, it doesn't matter what we transplant, right? So encapsulation, you know, these are groups like the what was formerly sigalon, which is now owned by by Eli Lilly, and the really beautiful work that's been done by the group at Aspect Biosystems in encapsulation inside of a 3D printed environment and there's been some really exciting developments there.

Mike Graffeo: 22:47

At its core, encapsulation always kind of competes with vascularization, so there's only so much nutrient and blood supply you can get when you're trying to encapsulate the cells. And there are signs of promise. There's also signs of challenge. Cigalon had to shut down one of their major programs because of late stage fibrosis of the encapsulated cells and really the materials that are used for encapsulation. The long-term kind of fibrotic impact is really unclear right now. So our belief is that encapsulation is still a challenge. It's not a soft problem and it really won't be until you see some compelling phase three data.

Jenny Chen: 23:29

Are these considered cell therapy in a category?

Mike Graffeo: 23:32

They are. It's interesting. Cell therapy in a category? They are, it's. It's interesting. You know, cell therapy in our industry generally is referring to like car t and these are one time you inject the cells they do the job and the job is over. So we see now with the um, with the type one application, we're starting to see the moniker of cell replacement therapy as a little different from cell therapy okay and so cell replacement therapy.

Mike Graffeo: 23:56

The cells are designed to go in and do the job from then until forever or for however long that you can achieve that. So you know, I think we use the term cell replacement therapy, ok, and to me that's that's just sort of a bridge to going from cell therapy to tissue Right. It's. Ultimately these will be tissue therapeutics. We're not quite ready to talk about that in the industry today. It's sort of one step too far for the way that most people think about it today. But I think this will be the application, that's the bridge.

Jenny Chen: 24:27

I mean, I think we're talking about it because the next thing we're thinking about is the regulatory pathway, because it's such a brand new thing. Actually, a couple months ago I saw out of jennifer lewis's lab they have an implant for breast cancer that's vascularized, but it's an implant plus cells in it. You know, I'm just wondering, like is your isocell implant similar in terms of the kind of combination device this is? I mean, how do you categorize it when you apply for any kind of FDA pathways, like, where do they put you?

Mike Graffeo: 25:02

Yeah, so you know, with our type one indication, that will definitely be a combination product. Okay, you know the Center for Biologics will be the lead on it, because the cells do the primary mode of action.

Jenny Chen: 25:14

I see.

Mike Graffeo: 25:15

But the CDRH will be involved because there's going to be cells deposited in an extracellular matrix scaffold and so CDRH, the devices center, will definitely be involved, and for us the CDER will also be involved. Cder, because our intent for our type 1 application is to load a local release, a kind of a depot of immunosuppressant just in the area of the implant.

Mike Graffeo: 25:41

So we envision all three centers involved from the FDA's perspective. There are other products that have done that. It's not a first of kind and fortunately for us, the cells as the primary mode of action for type one is not unfamiliar to the agency. So we think from a regulatory strategy perspective it makes a lot of sense to start here Because while there are definitely some open questions to answer, the road is actually somewhat clear to see how it will play out.

Jenny Chen: 26:11

Yeah, you know, it's really funny. Last Thursday we had a demo day, as you know, and a couple of investors, I mean, I heard the word doge quite a few times. Do you think doge is going to help?

Mike Graffeo: 26:25

You know it's an interesting question. I've been working with the FDA for 25 years. I've got four different FDA approvals in my career and I probably have a different point of view on this than a lot of folks, which is I've generally seen out of the FDA that when you work with them the right way there's a tremendous willingness to work with industry to solve real problems. So I'm not sure that you know FDA is broken and it needs a lot of fixing and overhaul is the right kind of mentality here. I think in general most folks at the FDA want to see novel therapeutics get to patients faster.

Jenny Chen: 27:01

Yeah.

Mike Graffeo: 27:01

So I think that you know, are there opportunities for efficiency? Absolutely Do. I think that you know the efforts that are being promoted right now through Doge will be potentially helpful.

Jenny Chen: 27:13

It certainly could be, or somewhere else maybe, tax for tax reasons.

Mike Graffeo: 27:17

Yeah, well, I mean, listen, there's inefficiency everywhere. Right, it's complicated, and it's complicated for a lot of reasons that didn't just happen overnight. So are there chances to do things better? I'm sure of it.

Jenny Chen: 27:28

Yeah, I mean I've encountered people who have to deal with the EU, have to deal with Singapore EU, you know, have to deal with Singapore government, chinese government, all these different regulatory bodies for healthcare, and everybody pretty much agrees that FDA is probably the best entity to look up. And you know, I would say okay, of all the bureaucracies, they probably actually I mean in my opinions I think FDA is probably the best of all the bureaucracies I've seen. So I mean in my opinions, I think FDA is probably the best of all the bureaucracies that I've seen so far.

Mike Graffeo: 27:57

I think that's right. I think that there's, you know, in the in all the different kind of mentalities. It's not just a what's the paperwork required, it's kind of what? What's the psychology behind why it's being done that way? I've always found FDA to be very done that way. I've always found FDA to be very, you know, just laser focused on as long as we can get comfortable that the risk is managed. We want to see the benefits out there for patients.

Jenny Chen: 28:23

Yeah, I think they're actually pretty innovative and try to be on top of things in terms of technology. Now, moving away from the serious technology regulatory talk, I want to go back to how you build your company, because how many people you have now in your company?

Mike Graffeo: 28:38

So we have 12 people today. Okay, we've been, you know, a couple of different phases of the company, so one time we were a little bit larger than that. When we moved away from the in vitro models back towards the therapeutic focus, we, you know, got a little bit leaner to be just really focused on that. Um, we've had, uh, you know, a couple of people join the team recently, some really top tier scientists that we've been able to add to the team, which is really great yeah, so when you just started, was adam, you just two of you there were three of us at the beginning, okay, and that was andrew or

Jenny Chen: 29:08

that's right, andrew. Yeah, that's right. And then, how do you um build a team? Because I, you know, noticed about you, mike, is that you have incredible soft skills. You're a very personable person and you always show up. I think that's the most important thing for founders. So tell us what are your challenges of building a team? How do you make sure you have the right team behind you for what you want to do?

Mike Graffeo: 29:33

Well, I think that the um, you know there's a couple of things that are really important there. You know number one uh, you know, you know when a lot of people get into whether it's entrepreneurship or leadership or otherwise, you get really wrapped around the axle, first on what do I do, what's the right thing to do, and the piece that I emphasize with my team and we've got some really tremendous young early career leaders in our team that are growing and developing I emphasize all the time to them that what you do matters, but it doesn't matter anywhere near as much as why you do it. You do matters, but it doesn't matter anywhere near as much as why you do it. When you care very much about the mission and when you care very much about the people that you're working with to achieve that mission, you can get away with not always doing the right thing, because people know how much you care and so they'll give you a little bit more rope, which lets you then try on and go do the things that you feel like you feel really important about with a little bit less. Oh my God, did I mess it up? And I think that's really the underrated thing that we understand about the world today.

Mike Graffeo: 30:36

When I was in my early career, people held up Steve Jobs as the picture, perfect example of how to do things right. And I got I don't know six, eight years later and Steve Jobs was held up as exactly the example of what not to do because he was this or that or the other thing. I look back at it and I say I think he was a terrific example of when you care that much about the product, your customers and your people, even if you mess up a lot and you know, let's not say it any other way, I could be a jerk Even then the kind of loyalty that you cultivate because of how much you care is infectious. So that's that's really number one. Like, if you're doing entrepreneurship, startup world, and you don't have that like I care so much about this down to my bones, you're probably not in the right spot. That's a really important piece of it.

Jenny Chen: 31:34

Yeah, I'm feeling like I. I. I loved Elon Musk for the longest time, until recently. I have to say he's acting a little bit out of my comfort zone, but I feel like he's the kind of person too. He's why he's, he answers why pretty well, for the last decade or so, except now. I don't know what's what is going on, what's going on with him, but it's always entertaining. That said, now if you have a new member coming in to your company, how do you mentor him? Do you advise him to read certain books to get onto the same page with you guys, or get a coach? How do you incorporate this new member into to make sure this person is comfortable?

Mike Graffeo: 32:22

Well, I can share with you a couple of examples the way that we think about when we hire, you know, a talented new scientist or engineer and she comes on board and we want to get them up to speed really quickly.

Jenny Chen: 32:34

Yeah.

Mike Graffeo: 32:35

The first thing that we tend to do is to say, okay, you know, we're always printing something.

Mike Graffeo: 32:41

We've always got some level of interesting work going on in the lab implants in the animal facility, otherwise so we want to get them hands-on really quickly. And so it's super important to say, all right, let's get up in the lab, spend some time shoulder-to-shoulder with our engineers, understand why we load the syringe the way that we do, understand why we program the G-code the way that we do and path things the way that we do, because this avoids this kind of trade-off and this actually sets things up better. This incorporates porosity a little bit differently. We're experimenting with this kind of shape versus that. We're experimenting with different concentrations of cells and otherwise. We want to get you in there and living and breathing the printing process, and that's in large part because we can hire tremendously talented people with backgrounds in biology and otherwise, and they can ask much better questions when they understand why the technology does what it does. So, shoulder to shoulder in the lab, seeing the experiments, understanding, you know people have a million questions when they start yeah they want to know why wait?

Mike Graffeo: 33:44

how does this do that? What's going on with this? So all of that happens in the lab. You got to be in there. You got to have the nitrile gloves on. That's step one. Step two is spending the time with my co-founders, with Adam, with Andrew Hudson, who've been living and breathing. How do I think about tissue engineering using fresh for now, 10, 12 years and just saying, all right, you know, let's really dig in on you, know what, what this technology unlocks and how you can use it. And then you know with, uh, with our PhD hires. So we just brought in a really talented scientist. Uh, she's got a great background in islet cell biology.

Jenny Chen: 34:25

Yeah, you said you, you hired a new scientist recently, right we?

Mike Graffeo: 34:28

did yeah, and so one of the first things that we do.

Jenny Chen: 34:30

Do you want to give her a shout out?

Mike Graffeo: 34:32

So yeah, so Fadma Dogan just joined our team about a week ago. She's been a tremendous hire for us. We're really fortunate to have been able to bring her into the company and one of the first things that we do is to say listen. You know, we've got a weekly science meeting. We bring all the PhDs together and that's where we talk about data interpretation and experimental design, thinking broader picture around. What are we doing next to make sure that we're asking and answering the right questions basis? We have the forum for that. You can really quickly get up to speed and understand. Okay, these are the questions the company's wrestling with right now. What kind of input do I have on these questions? And I think it's also really important to me that, just structurally, we create space and we really want those questions to come out, so we try to create an environment that's going to draw those questions out.

Mike Graffeo: 35:22

I don't like to reference Steve Jobs multiple times in a podcast, but one of my favorite leadership quotes was one of his where he said listen, we don't hire smart people and tell them what to do. We hire smart people so that they can tell us what to do.

Jenny Chen: 35:36

I like Steve Jobs. I think he's a great guy, except I won't work for him and also I didn't have the opportunity to work. But yeah, I love him too. So Adam is studying chronic melan at the moment, are you guys?

Mike Graffeo: 35:58

how do you guys get together and continue to have the cohesiveness, even though at different lab locations? Yeah, so Adam's our CTO. He's been our CTO since we founded the company.

Jenny Chen: 36:03

Right.

Mike Graffeo: 36:04

And he's a brilliant scientist who's done some of the most advanced work in this field.

Jenny Chen: 36:09

For a long time. Absolutely, he published every single paper. I was like I want to read that. Absolutely, he picked the right topic.

Mike Graffeo: 36:14

His lab. They do phenomenal work and his lab is, by and large, leveraging this technology in most of what they're doing. So it's also really fertile ground for early, early stage R&D for what the company will be doing next. So if you want to know what Fluidform is going to be doing in three, four, five years, go take a look at some of the things that are happening inside the lab at Carnegie Mellon.

Jenny Chen: 36:36

Well, he published a paper focusing on AI and bioprinting a couple of years back.

Mike Graffeo: 36:40

Yeah, one of the earliest ones in the field.

Jenny Chen: 36:42

So I wonder when you guys are going to use AI to put AI in your pitch deck.

Mike Graffeo: 36:46

Well, stay tuned 2025, we've got some really exciting developments. There will be several things on that front.

Jenny Chen: 36:53

Look forward to it. Well, you have so many things to do in life. How do you balance, I mean, when you first wanted to start this startup kind of high risk, I would say.

Mike Graffeo: 37:06

Everyone is yeah.

Jenny Chen: 37:08

How did your wife respond to it?

Mike Graffeo: 37:12

I am incredibly blessed to be married to a partner who has a lot of patience and understanding around when I get lit up about an idea, like letting me run with it. So, you know, we we had a long talk. I told her I was missing startups and I think maybe I wanted to do it again, and she, you know, wanted to ask the questions like help me understand what it is that you're thinking about and why, and you know what is it that makes you feel like that's the right thing for you. And you know, when we, when we had that discussion, she was really supportive of it. So you know, I feel really blessed that she was that that she was able to say to me look, if this is what you got to do, like, go do it, but just go do it well, um, and so, yeah, having that kind of support and partnership has made a huge difference.

Jenny Chen: 38:01

I mean, that is probably one of the few choices in life that's really impactful in our lives as our life partners. Okay, well, final question for you For 2025, okay, I personally think the source of information is extremely important for our daily life and decision-making. How do you, what are some of the recommendations you would have for people to get the best information available, either for bioprinting or biotech or life in general? Do you have any recommendations for people's like reading list, podcasts, youtube channels and stuff? Just throw it out there, sure.

Mike Graffeo: 38:42

Sure Well, first off, if you're interested in learning about bioprinting, I would start with the Fluidform social channels.

Jenny Chen: 38:48

Okay, yes, we'll share the link we definitely have.

Mike Graffeo: 38:51

we've got some really good material there. There's more coming. We're going to be able to be a little bit more public about the work that we're doing and why we're so excited about it. So follow along there Twitter, linkedin and, of course, if you're looking to know what's going on in the 3D bioprinting world, even larger than just fluid form, you should be following along with 3DHeal.

Jenny Chen: 39:08

Oh, thanks, that's kind of you.

Mike Graffeo: 39:10

And then you know, I think, just broader. You know so when it comes to what's going on in biotherapeutics writ large. I get most of my daily updates from the group at Stat News, which is a subsidiary publication out of the Boston Globe News, which is a subsidiary publication out of the Boston Globe. The reporters there do an awesome job and it's really easy to stay on top of what's going on in the industry Kind of the single source there. There's other really great resources Endpoints News and others that are terrific, but I think that picking one or two of those and staying on top of it really helps. One or two of those and staying on top of it really helps For me.

Mike Graffeo: 39:46

The other thing that I think about is what am I doing to cultivate? You know the sort of sense of steadiness in the world and I've spent a lot of time at the intersection of. You know different philosophies and approaches around this, but I think whether you're getting some daily psychological nourishment from you know somebody like Ryan Holiday and the daily stoic practices, or you know Buddhism or religious traditions or otherwise, the consistent theme of remember there are things in this life you can control and things in this life that you can't, and you really ought to be focused on the things in life that you can control, which largely exists between the ears. Um, that's really nourishing and really helpful, because you know it's it's all hard, there's no, there's no easy path in anything anymore.

Jenny Chen: 40:36

Do you find different books to get that piece of philosophical calmness or do you just go to a one source? You know that like a set of quotes or app or something for that kind of comfort.

Mike Graffeo: 40:49

Yeah, so I love reading books. I read all kinds of books. If Ryan Holiday publishes something, I'll read it.

Jenny Chen: 40:55

He's just he's a must read as far as I'm concerned.

Mike Graffeo: 40:58

Absolutely. I think that you know there's a lot of that message woven into, if you like, podcasts, woven into various of the Tim Ferriss interviews as well. Several of those are great and I think that when you, you know, when you, depending on a religious, inclination.

Jenny Chen: 41:18

Most of the world's religious traditions also teach that in one way or another. Right, exactly, yeah, I agree. I think religion actually on fundamental stuff, is similar to one another.

Mike Graffeo: 41:24

Absolutely yeah. Be a good person, try not to worry about the stuff you can't control. These are universal things.

Jenny Chen: 41:30

Yeah, I actually just finished the book how to Think Like a Roman Emperor. I don't know if you've heard of that I've heard of it.

Mike Graffeo: 41:38

I've not read it.

Jenny Chen: 41:38

It's a newer version of a regurgitation of Marcus Aurelius' meditation, and that's exactly what I said Just be. The goal is actually not to be happy. The goal is to be a good person, so I will end on that note. Thank you very much, mike, for joining us in the studio today with our duct taped camera and overnight shipped microphones. Thank you very much.

Mike Graffeo: 42:03

Thanks for having me, it's been great.

Jenny Chen: 42:04

Come by next time.