New Matter: Inside the Minds of SLAS Scientists
New Matter: Inside the Minds of SLAS Scientists
Revolutionizing Healthcare with Bioprinting | with Didarul Bhuiyan, Ph.D.
The pace at which bioprinting technology is advancing shows that it is not just a passing trend, but rather a powerful force that's revolutionizing healthcare.
To better understand the current state of bioprinting and its clinical applications, we're joined by bioprinting expert Didarul Bhuiyan, Ph.D., Sr. Scientist, R&D - Bioprinting at West Pharmaceuticals Services. Didarul shares his expertise in the field, explaining the differences between bioprinting and traditional 3D printing, the challenges faced when using cells in the 3D bioprinting process and the materials used in bioinks for this technology.
Key Learning Points:
- What all is involved with bioprinting
- How bioprinting can revolutionize preclinical drug discovery
- The current challenges facing bioprinting technology
- The opportunities for automation within bioprinting workflows
- How hospitals could use bioprinting technology
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SLAS (Society for Laboratory Automation and Screening) is an international professional society of academic, industry and government life sciences researchers and the developers and providers of laboratory automation technology. The SLAS mission is to bring together researchers in academia, industry and government to advance life sciences discovery and technology via education, knowledge exchange and global community building.
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Hannah Rosen
Hello everyone and welcome to New Matter, the SLAS podcast where we interview life science luminaries. I'm your host, Hannah Rosen, and joining me today is Didarul Bhuiyan, senior scientist at West Pharmaceutical Services. We will be discussing bioprinting, where it is now and what we need to do to use it for clinical applications. Welcome to the podcast, Didarul.
Didarul Bhuiyan
Thank you so much, Hannah. Thank you for having me today. I'm very excited to talk about bioprinting.
Hannah Rosen
Oh, we're really excited to talk about it too, I can tell you that. To start off with, can you just give us a brief description of your professional background and your expertise?
Didarul Bhuiyan
Absolutely. I'm a biomedical engineering PhD, expertise in the biomaterials and tissue engineering, an extensive focus in 3D biofabrication and bioprinting. I have been working in this field for about 12 years now. During my PhD, I developed a polymeric biomaterial for bone regeneration application. Then I spent a few years as a postdoc and was working on bioprinting a centimeter-scale beating heart. That's where my journey in the bioprinting space started. Then I transitioned from academia to industry and I worked for a globally leading life science reagents company and as a lead scientist I was responsible for building the bio-ink product portfolio over there. As you mentioned, I'm currently working as a senior scientist in the West Pharmaceutical Services R and D, and a resource goal for us now is to enable the clinical transition of bioprinting workflow through containment, storage and transportation solutions and delivery devices for bio-ink and tissue engineering medicinal products.
Hannah Rosen
That's so cool. I know for me personally, and I think it's probably true of a lot of people when we think of this 3D printing, I always just picture the plastics where you've got the printers going and it just automatically creates a 3D version of the thing you're printing using plastics. Can you go into a little bit more detail of how does 3D bioprinting work and how is it different from 3D printing with more traditional materials like plastics?
Didarul Bhuiyan
Absolutely. That's a really great question. I get that a lot as well. 3D printing, as you were mentioning, most cases plastic and nowadays pretty much any material like metal, ceramic and so on are used. You know the process is basically depositing those materials layer by layer to create a three-dimensional object.
Bioprinting or 3D bioprinting very often referred as a biological cousin of traditional 3D printing. The key difference here is biological materials. Most cases leaving cells are used in this 3D printing process. The leaving cells are deposited on layer by layer fashion to create three-dimensional tissue constructs. The materials often called bioinks those are hydrogel materials that contains those cells during this bioprinting process.
Most commonly the materials that are used for 3D printing, the cells do not really like them, they do not really grow on them, they don't function as they are supposed to do. On the other hand, the materials that we know that cells really like the materials that are traditionally used for cell culture and those kind of application those materials are typically not good for 3D printing. That's where the biggest challenge lies and that's where the bioprinting differs from traditional 3D printing. Also, you can also imagine in traditional 3D printing the temperature or other parameters, other processes like exposure to different kinds of laser or lights that are typically used, but for bioprinting those may not be good for the cells. For bioprinting, that's how it is different than the traditional bioprinting, because all these processes needs to be very cell-friendly The materials that are used, that needs to be very cell-friendly. That's where most of the challenges also lies for bioprinting than traditional 3D printing.
Hannah Rosen
Yeah, that sounds super challenging. if the cells are just not happy in this 3D printing environment, could you maybe go to a little more details of the materials you're using for these bio inks? You said that it sometimes contains the cells, but if the cells don't like the materials in the bioink, what do you do to work around that?
Didarul Bhuiyan
Absolutely. Let me just explain a little bit on the bioink first. Bioink are mostly the very highly viscous aqua solutions that encapsulate the cells during the bioprinting process. Different biopolymers are typically used in a very highly concentrated fashion And a lot of proteins, growth factors and other molecules are also used in that formulation to basically provide the information to the cells, to control their fate, basically to inform them hey guys, you need to be alive, you need to grow, you need to go into certain direction or mature it, what we call it to function as a tissue. So that's how the bioinks are formulated right now.
As I was mentioning, a lot of cases these bioink materials are not very robust or creating a three-dimensional shape in a very high fidelity fashion. So that's where we are basically compromising a little bit on the biological side of a lot of cases to achieve the printing function, and a lot of cases we are compromising on the printing fidelity side to achieve a lot of biological function. So that's where the current status of the field, but a lot of innovation, a lot of research is going on to develop new and new biomaterials to solve this need and have more self-instructive printable materials.
Hannah Rosen
So now, when you're printing these, are you using any sort of scaffolding to kind of help to shape the materials, or are you just printing it completely freeform?
Didarul Bhuiyan
Exactly. There are many different processes that the field has come up with to mitigate those challenges. When it all started, it was very interesting. About 20 years ago. First, HP Inkjet printer, which typically is used for printing documents and such, was modified for printing cells. Basically, just the ink cartridge was removed and it was filled with cell solution and was printed on a bio-material, which was called at that time bio paper, instead of the regular paper and the cells were patterned in that surface. That's how it all started.
It has gone through a lot of evolution in terms of the printing technique. Many printing modality also emerged. Some are extrusion-based, some are light curing-based and some are with acoustic and other different factors. If we're thinking about a typical extrusion-based technique, a lot of cases as I mentioned the cell-friendly materials they cannot self-support to make a 3D structure. In those cases, a lot of occasions supporting structure are also created as they are printed. Those supporting structures, a lot of cases are sacrificial. After printing those are basically removed to obtain the required geometry and shape that we want.
Hannah Rosen
That's so interesting. It sounds like there's a lot of different ways that people are tackling this problem. It's not so much of just like here's the way to do it, it's well, you could do it this way or you could do it this way. That's really interesting and probably because it's still so early in the development stage, I imagine that everybody's trying to come at it different ways to find the best way to solve these problems.
Didarul Bhuiyan
Exactly.
Hannah Rosen
Are there any special considerations required working with this bio-ink in terms of storage.
Didarul Bhuiyan
No, exactly, there are a lot of considerations and challenges in terms of that clinical translation from these research outputs to make it more amenable for clinical setting, for example, extrusion-based bioprinting that I mentioned. In extrusion setting the cells go through a lot of here and that basically damages the cells and eventually the cells lose their function or they die during that process. So to make that more cell-friendly process is very challenging and that's where the container where these cells and the bio-inks are contained, also very important and can play a very critical role to minimize those kind of shear through the material property of the containment system and the geometry and the design of those as well. Similarly, in terms of the storage and the transportation, as you were also mentioning, these are very critical considerations. If we think about biologic products out in the market right now, the sterility of those materials are very important. So when we are thinking about bio-inks that are very vital building blocks for making those bioprinted therapeutic products and very expensive products, that the container also should maintain all those standards that is maintained for the biologics.
So, for example, storage conditions for biologics are for the cells that goes to very cold temperature in liquid nitrogen. So the container closer, integrity of those containers should be maintained in those kind of conditions. The quality of that product, the quality of the bio-inks and the cells should not be compromised in any way during that storage and transportation process So that container material should have all those properties to meet those demands. Also, the container should not be reactive, should not be additive, should not have any sort of negative impact on the materials that are being contained in those kind of conditions so that the predetermined properties of those bio-inks physiological property as well as the biological property are maintained. Also I would like to highlight that in those containers there are movable pieces, there are pistons, there are barrels, so there are a lot of friction and those kind of mechanism goes on. So that may also generate particulates that also can get into the bioprinted product eventually, which can impact the patient's safety eventually if they have any pyrogenic property for example. So those should be considered when these kind of containment systems are being designed.
Hannah Rosen
Yeah, that's a lot. It sounds a lot to consider, which I mean, shouldn't be entirely unexpected, I would imagine. So you talked about you're now trying to focus on getting this 3D bioprinting from the research into the clinical and therapeutic stage. What is 3D bioprinting currently being used for?
Didarul Bhuiyan
Sure. So, as I mentioned, it's a relatively new field. About 20 years ago the first research publication that came out and within last 10 years or so the field has seen tremendous progress. There are exponential growth in the research publication. Centimeters scale, a miniaturized tissues and organs are routinely being built in the academic setting. So tremendous potential of this field.
So two major application areas in the healthcare sector that we can very easily see One is in the drug testing for preclinical drug testing discovery research area, most cases there's animal models that are being used in the preclinical stage when these drug molecules are being tested They really don't recapitulate the human physiology properly And that results in more than 90% drugs basically fails when they transition from preclinical to clinical stage. That's where there's a huge need for a reliable model system for recapitulating the human physiology in three dimension And that's where bio printing being used right now and has a lot of potential being the reliable system or model for the drug discovery research purpose And, on the other hand, the biggest impact the bio printing can have, what we feel is in the regenerative medicine field, in the transplantation or implantable area.
So right now in the US alone there are more than 110,000 people are in the organ waiting list. More than 20 people basically die every day while waiting for an organ. So there's a huge organ shortest crisis that is going on in this world.
So there is a huge demand for a manufacturer tissue manufactured organ And the bio printing has the biggest potential to solve that crisis And a major milestone that we have seen in the field last year, the first bio printed product was implanted in human patient as a part of a historic clinical trial that is going on right now And we are very hopeful. Through that, it's basically you're going to pave the way for magnitude of this bio printed research output to translate into clinical reality.
Hannah Rosen
So wow, I have a lot of questions regarding that. You know organ regeneration thing, but I do, before we get into that too much, I want to circle back a little bit to something that you said earlier about the use of the 3D printing for the drug discovery process. I'm wondering you know, how will these, or how do these 3D bio printed models compare with other 3D models that currently are developed? Like you know, are you essentially. Are they creating essentially organoids, or is it something completely new and different?
Didarul Bhuiyan
These are still in the evaluation phase, I would say. So there are a lot of interest from the pharmaceutical industry to utilize this tool to create this kind of reliable 3D model systems to eliminate the need of animal models.
And also, traditionally they were used, they were using two dimensional cell culture for for this kind of drug molecules testing. That was not really translating into anything when when they're going for the clinical trial. So right now, the bio printed tissues in in a miniaturized scale that are being evaluated And that can be integrated in you might have heard about lab on a chip or our body on a chip, organ on a chip and those kind of terms. So that's where this bio printed miniaturized tissues can be integrated into a chip or kind of microfluidic device where they are interconnected And that's where you can basically test the effect of a drug molecule in terms of the interplay between the organs as well, for example from from heart to lung and lung to heart and kidney and so on. So that's where the field right now in terms of research but still early stage there are no real standards, i would say, in the field And as, as we progress there are these devices and these organoids are going to be more standardized, I feel, towards particular applications and particular tests and needs.
Hannah Rosen
Wow, that's really, that's really cool. Can you just kind of briefly describe for us what a typical 3D bio printing workflow looks like?
Didarul Bhuiyan
Absolutely. That's a very good question. 3D bio printing workflow, as you can imagine, a lot of cells are involved. I was also mentioning about the bio-inks before, so those are the two major components for bio printing. So cells are typically grown in a very large scale and then, when they're ready, they're typically mixed with bio inks. As you can imagine, it's in the research field right now. So a lot of cases these are done very, in a very manual processes. Through that those mixture of the cells and the bio inks are transferred into cartridges that are compatible with the bio printer And then basically bio printers spits them out into the specific geometry and shape that we define. And then this, this construct, is cultured in an incubator or the typical cell culture environment a lot of cases in bioreactor to mature it into a functional tissue, and that process also may take from weeks to even couple of months in some cases.
Hannah Rosen
Oh, wow, I didn't realize it took such a long time. Do you anticipate that that's probably always going to be about the time scale we're working with, or do you think that as we improve our techniques and the tools and equipment that that timeline will shorten?
Didarul Bhuiyan
So, as of the biology, right now that is the time we have to give the cells to basically grow, interplay with the material they are in or the environment they are in, and eventually grow into tissue. But who knows, in future, with the progress in the biological field, maybe we can accelerate some of this process and shorten the time.
Hannah Rosen
Wow. So what sorts of, when you look at this workflow, you know, where do you see opportunities for automation within the workflow? You know, I'm assuming that the 3D printing process itself is fairly automated. But you know, when you look at these workflows, are they fairly manual or, you know, is it already fairly automated or, if it's not, you know, do you think that it will become more automated in the future?
Didarul Bhuiyan
Absolutely, that's a great question. So that's what I was trying to mention in the previous point as well, that the cells and the bio-inks, those are the two major components and in research environment, most cases manual processes are involved for their culture, for their transferring from one to another, and the cells are lifted to manual process and then mixed with these bio-inks in very manual processes and then transferred into a cartridge, that is, that goes into the bioprinter. Those are also very manual. So, and you can imagine, in the clinical setting these really are not acceptable. That has a lot of risk in terms of contamination, in terms of variability.
So we see there are a lot of opportunity for automation of this workflow and integrated devices and the containers where this, the starting materials for bioprinting are contained, can play a big role in terms of having that integrated into an automated workflow. Sensor technologies are also very important that can basically enable the process control mechanism or for automation. So those, I think, are the critical parameters for translation of this manual processes to automated process, which we are looking forward to in future.
Hannah Rosen
Now, when you're thinking about I'm curious thinking about transitioning this over into the clinical setting. you mentioned some of the potential clinical uses, including eventually perhaps generating organs for transplants, et cetera. I wonder can you just go a little bit more into that? Are you thinking basically creating an entire kidney from scratch, or are we thinking more of like for a skin graft we can make a section of the tissue or like a liver transplant, a section of liver? What kind of the scales are you looking at And what are the timelines that you think that these will be implemented?
Didarul Bhuiyan
Great question. So no, absolutely that is the ultimate goal to create those implantable organs for treating those patients and basically solving that organ shortage crisis. But that will definitely. we are not there for sure. So there are major challenges, very, very big challenges. For example, how do we create those intricate blood vessel network to supply the oxygen or the nutrients to the cells that are in that clinically relevant scale, tissue or organ construct? So there are printers available right now that can basically manipulate the cells in a single cell level, But those are not super fast to create those kind of big structures. So something would still a lot to go for us to create those kind of printers that can go down to very minute detail as well as can create a very big structure very fast.
At the same time, I mentioned about the biomaterials. there are not many options for us to utilize the materials for this kind of application because a lot of cell friendly materials they are really not printing friendly. So how can we make more and more better materials, cell instructive materials that can basically be printable? So there are a lot of those kind of technical challenges that needs to be resolved, as well as there are other hurdles in terms of the whole clinical translation of the bioprinting research to clinic. that we see are in terms of the containment as well. So there are not a lot of GMP graded containment system available in the market. There is a very limited number of GMP graded materials available. So those are really needed if we are thinking about the clinical application.
In a lot of cases these materials, even they are GMP graded, they need to be reformulated or formulated in the user end so which are also not very clinical use friendly because there are risks of, as I said, the contamination variability in those kind of conditions.
So those are some of the challenges that needs to be resolved right now. but we see that progression towards the clinic. So we see that last year that clinical trial started on the bioprinted year that was implanted on human patient. So that will pave the way that will also tell us, the regulators and the entire industry, what we should expect for that regulatory journey of these kind of products And that will eventually pave the way for some simpler structures. And I'm saying simpler is really not simple, but compared to a full, solid organ they might be a lower hanging fruit. So in that direction, maybe skin or some vascular graft, those kind of products may follow after a year, And then those will eventually pave the way for some hollow organs like bladder and things like that, And eventually solid organs will be built, hopefully somewhere very in near future.
Hannah Rosen
So if there is a researcher out there who is currently listening to this podcast and they are super interested in collaborating or utilizing this 3D bio printing, especially in the realm of drug discovery we have a huge membership that's working in the field of drug discovery. What do they need to know? What should they do if they want to kind of get in on this work?
Didarul Bhuiyan
Absolutely. So, as I mentioned that two major applications of bio printing that are very, very promising in the healthcare sector drug discovery, for sure, is one, and another is the implantable tissue and organ generation. Standards are very much needed in this kind of interdisciplinary field because the components need to be interoperable, so the bio inks and the cells and the hardware, the bio printer, they all need to be compatible with each other when we are thinking about eventually creating a tissue, either for drug discovery application or for therapeutic application. So that's where there are a lot of standards development organizations are working on to create those standards And from West Pharmaceuticals we are also contributing in those efforts. We are a member of a consortia called Advanced Regenerative Manufacturing Institute, or ARMI, and they have a program called BioFab USA And through that collaboration we are basically contributing to different standards development activity led by standards development organizations like ASTM, ASME, SCB, and such.
But overall we see these bio printed products are rapidly progressing towards clinic. There are a lot of investment from this, corporate collaborations and that's what is driving this huge progress in this field. But further industry-wide collaboration is required between the therapy developers and the tool providers, for example the bio printer makers, bioink makers and the containment system and those kind of supporting tool provider for this entire workflow And this kind of collaboration will basically accelerate the translation of this magnificent research output that we have seen in last decade in the research area to translate into clinical reality to eventually solve the organ shortest crisis in near future.
Hannah Rosen
Wow, I mean, that's just a lot to think about, a lot to be excited about and to look forward to, to be sure. Didarul, thank you so much for joining me today. It's been a real pleasure talking to you today and getting to learn more about this exciting new field and to hear about you know what we can look forward to, And we really hope to see you and West Pharma at some future SLAS events and really look forward to kind of seeing where the future takes this.
Didarul Bhuiyan
Thank you so much, Hannah. Thank you again for inviting me to talk today. Really enjoyed our conversation. Yeah, we're looking forward to connecting again soon.
