3D printing has been around for almost 10 years since it went “mainstream” and one of the first thoughts that everyone had were the possible applications in healthcare. Many positive articles including 3D printed heart models, 3D printed prosthetics, 3D printed implants have been published.
These stories are amazing, and the progress 3D printing has brought to healthcare has been great, yet it is nowhere near the scale that people have envisioned for it. Still, the majority of prosthetics and orthotics are created with traditional methods. Casts are made with the same old plaster of Paris. Same goes for implants. How so? What is the reason why it`s not already become widely used? Are the costs too high? Maybe. But I believe that the key lies in the form of listening to all stakeholders involved in healthcare services. This includes doctors, nurses, clinic management, technicians, insurance representatives, regulator and, of course, the patient. It is common that new innovations more commonly come from people with a technical background (engineers, developers, etc.), however, in healthcare innovators must think about the process and systems as much as about the product or service. Here`s why:
Operating 3D printers, modeling, file preparation – it takes time!
When introducing a 3D printed product or service in a clinic, it becomes clear from a process standpoint that 3D printing is not so easy at all and can become quite complex. Do any clinicians have free time to “play” with their 3D printers? No. Do nurses have free time? Also no. Who does?! Large university hospitals or private hospitals have a separate research and technical departments that can maintain, launch and post-process the 3D prints. But what about the hospitals who do not have such departments? Or local clinics who also would benefit from having access to 3D printing technology? Because of this, companies such as Materialise or services such as Shapeways have come into play, to take part in the time-consuming tasks away and make it more accessible for clinicians to use 3D printed technology.
2. What happens if something goes wrong? Who`s responsible?
When 3D printed products reach patients, such as 3D implants or 3D casts, how does the accountability work? If 3D printing is done by company X, 3D modeling by company Y and 3D scanning by the clinic, how to ensure quality checks? If something should go wrong, it`s highly likely that the blaming game would start. Company Y would say that the scan was faulty, thus the model was not precise. Or Company X would say that the model was bad, that’s why the 3D print, in the end, was not good. And so on. If you have such risk, it`s no wonder the general medical community is not too eager to introduce such technology to their patients. One of the way new technology companies solve this, by providing end-to-end services, such as CastPrint, that provides clinics with all the services (software and hardware) so that there are clear lines of responsibility.
3. Who will pay for it?
Traditional medical device manufacturers have long outstanding relationships developed over the years with the industry, thus it is easier to sell several hundred thousand worths of equipment. Unfortunately, 3D printing does have such a history, thus each purchase is carefully evaluated for economical and clinical value. Moreover, of a 3D printed services or product would be re-charged to the patient, would the insurance cover it? One of the ways how to avoid any surprises insurance coverage, is to develop relationships with the insurance companies sooner than later, while still developing your 3D product or services, thus once it’s on the market, insurance would cover the services or product and clinics would be more willing to offer it to their patients.
To summarize, in order to bring 3D printing to the general public and “mainstream” healthcare there is still lots of work to be done. Innovators and startups have to closely work with the medical community and develop their 3D printed products and services taking into consideration existing systems and process in place and how would it change using the new services or product. Even if the 3D printed product is better, but it is significantly more challenging to offer it by clinicians than traditional products, it is highly likely that no one will prescribe it. However, if the 3D printed product or service would not only be better than traditional methods but also be easily accessible for the clinicians and all other stakeholders, then 3D printing will eventually become in healthcare such as common as an x-ray machine or a statoscope.
About the Author:
Sigvards Krongorns is the co-founder of CastPrint, a 3D printed medical technology company specializing in 3D printed casts for fracture injury treatment. Sigvards has a background in business administration from RISEBA University (Riga, Latvia) and for the past years has been working through CastPrint to bring 3D printed technology to “mainstream” healthcare.
Exciting things are happening in the fields of tissue engineering and regenerative medicine, all thanks to 3D bioprinting. The high precision and convenient operation allow 3D bioprinting to expand into new areas. Current research efforts all over the world are now leading to innovations in regenerative medicine, vascularized printed organs and replicating organ functionalization. However, to attain reproducibility or to print clinically relevant forms and sizes, material control is important. The implementation of bioprinting relies on the geometrical accuracy of replicating the design file. This, in turn, depends on printing parameters and material properties. Studying and understanding the correlation between hydrogel material characteristics and successful bioprinting is important to obtain functional 3d constructs to fulfill intended applications. Much research has been done on ink properties and printing optimization. However, little attention has been paid to the relation between hydrogel parameters and printing fidelity. Most of the users are uninformed about the properties of hydrogels that should be kept in mind for obtaining a good 3D printed construct for the intended application. There are many material parameters that influence the printing process and resolution directly and can be tuned to achieve a finely tuned process.
3D multilayer structure printed using Alginate hydrogel bioinks.
Be mindful of Gelation Time
Not all hydrogels are created equal. Gelation time in hydrogel varies according to their crosslinking chemistry. This parameter has to be kept in mind when choosing a hydrogel for a particular application. Collagen has been found to be the slowest to gel so far [1].
How is the swelling?
Swelling is defined as the ratio of the mass of swollen hydrogel to the mass at the equilibrium. Swelling contractile characteristics can be of central concern for producing biological constructs especially for skin and wound applications. The swelling rate also governs the stability, as one would want the bioprinted hydrogel to be in place for a sufficient amount of time.
Against the gravity
Care has to be taken to avoid diffusion of hydrogels in one another when overlapping layers are printed. The diffusion phenomenon will make the printed pores to decrease in diameter when printing more layers. For a lattice structure, with an increase in line distance, the diffusion rate can be slowed down thus reducing the diffusion effect (fig 1).
Figure 1: Graph depicting the relationship between line distance and diffusion rate in a lattice structure (reprinted with permission from ref. 2)].
Control your curves
Fabricating sharp angles through 3D bioprinting is a challenge. Sharp bends create material overlap resulting in non-uniform thickness, which eventually leads to printing failures. Most of the time the construct has to be re-designed to avoid such issues. An alternate way is to reduce the extrusion rate for such prints.
The Game of Viscosity
This material property is the most important and well-understood for printing. For hydrogels, the viscosity (η) should ideally lie between 300-30000 cps (centipoise) for most printers. Although attempts have been made to print hydrogels with η˃30000 cps using higher pressure systems, however, the printing is not reproducible and stable with time.
References:
[1]. S. V. Murphy, A. Skardal, A. Atala, Evaluation of hydrogels for bio-printing applications, Journal of Biomedical Materials Research 101A (2013) 272-284.
[2]. Y. He, F. F. Yang, H. M. Zhao, Q. Gao, B. Xia, J. Z. Fu, Research on the printability of hydrogels in 3D bioprinting, Scientific Reports 6 (2016) 29977.
About the Author:
Shweta Agarwala is Assistant professor at Department of Engineering, Aarhus University (Denmark). Dr. Agarwala graduated in electronics engineering from Nanyang Technological University, Singapore and obtained her Ph.D. in the same field from the National University of Singapore. Her research is directed towards printed electronics for flexible devices and bioelectronics. She is pioneering new routes to put electronics on unconventional surfaces to enable future generation healthcare.
Boyle Suwono,Structo Chief Technology Officer. As CTO, Boyle is responsible for building and scaling the technology development team in Structo, spanning from hardware, software, and material. He was responsible for the design and development of DentaForm®, a high throughput dental 3D printer with MSLA technology. He also was responsible for initiating, developing and delivering first-in-the-industry bespoke high volume fully automated 3D printing solution based on DentaForm®. He also co-invented Velox and Elements, first-in-the-industry fully integrated end-to-end 3D printing solution for consumer and industrial application respectively. He joined Structo from Schlumberger in 2014, where he was responsible for full system integration development of Crack the Paleogene (CtP), an ultra-high reliability downhole pump project for high pressure and high-temperature wells in the Gulf of Mexico. Boyle received his B.Eng. in Mechanical Engineering from the National University of Singapore. He will be speaking at the upcoming 3DHEALS Annual Singapore event on August 28th, 2019.
Jenny: When was the first encounter you had with 3D printing? What was that experience like? What were you thinking at that moment?
Boyle: Messy! My first real encounter with 3D printing was with Structo, and it was resin 3D printing. My thought was it was a pain to 3D print because of how involved and dirty the whole process is.
ClearCap uses Structo printers for large volume production of dental aligner models
Jenny: What inspired you to start your career in 3D printing?
Boyle: I wanted to be involved in a new exciting technology that is not purely software, and wanted to experience startup. My juniors back in the university started Structo and periodically asked me to join. After some point, I thought, let’s just do it. And there’s that.
Jenny: Who inspired you the most along this journey in 3D printing?
Boyle: No one in particular, but in general my colleagues in Structo. They are a bunch of hungry and passionate group of people who want to make a great product for the customers. Working with them every day is inspiring.
Jenny: What motivates you the most for your work?
Boyle: To introduce new cool stuff to the industry that has never been done before. Velox is a great example of that – before Velox, post-processing is a given. It took someone from outside the industry to change that. And of course, to see plan comes together is always very satisfying.
Jenny: What is/are the biggest obstacle(s) in your line of work?
Boyle: Hiring. It is a constant challenge to get great people, and not just technical people. We are always on the lookout for great talents.
Jenny: What do you think is (are) the biggest challenge(s) in 3D Printing/bio-printing? What do you think the potential solution(s) is (are)?
Boyle: Material and software workflow. Material, because that is the heart of 3D printing. The material needs to suit the application and is where the majority of the challenge is. In general, the property of 3D printed material is still inferior compared to another manufacturing method. Software workflow, because ultimately the users don’t want to work so hard to get something printed. Digital dentistry is a great example of that.
Jenny: What advice would you give to a smart driven college student in the “real world”? What bad advice you heard should they ignore?
Boyle: Find a hobby, and even if you eventually can’t find one, at least you try many new things in the process. Having a hobby is a privilege and in my opinion, makes you that much more interesting. Bad advice? That everything you learn in school will be thrown away and is useless. I think this is taken totally out of context. In the technical field, at least, the fundamentals that are learned in school is very important, and for some reason, it seems to be less and less appreciated.
Jenny: What was/is the biggest risk you took in your career?
Boyle: Joining Structo!
Jenny: What do you enjoy in your spare time? What are you passionate about outside of your work/3d printing?
Boyle: I really enjoy DIY projects. The most recent one was making my own wooden dinner table. Also playing guitar.
Jenny: What does the word “3DHEALS” mean to you? =)
Boyle: 3D printing in the medical (and dental) industry!
Dr. Raymond Wonggraduated with a Bachelor of Dental Surgery from the University of Malaya. While there, he won the University Entrance Scholarship and won the Book Prize for Excellence for the First, Second and Final Professional Examinations (Part 1). He then pursued his specialist training in Oral and Maxillofacial Surgery (OMFS) at the National University of Singapore under the Association of Southeast Asian Nations (ASEAN) Post Graduate Scholarship, graduating with a Master of Dental Surgery (OMFS). He subsequently went on to work as a Specialist Registrar at the Sunderland Royal Hospital and a Clinical Fellow at Morriston Hospital, Swansea, Wales in the United Kingdom while on a Health Manpower Development Program under the Ministry of Health Singapore. He obtained a Ph.D. in Medical Sciences from the Radboud University of Nijmegen, the Netherlands. He is a Senior Consultant and Assistant Professor in OMFS at the National University Centre for Oral Health and the National University of Singapore. At the University Level, he is the co-thrust lead for Dentistry, AM.NUS. Dr. Wong was a Past President, Association of Oral and Maxillofacial Surgeons Singapore, sits on the Specialist Training Committee, OMFS, represents Singapore as Country Councilor on the Asian Association of Oral and Maxillofacial Surgeons as well as holds a Councilor at Large post on the Executive Council of the Asian Association of OMFS and the International Association of OMFS as Singapore Councilor. He serves as a Regional Faculty, Association for the Study of Internal Fixation (AO) Craniomaxillofacial Surgery (AOCMF) at the Asia Pacific region. AOCMF is a nonprofit educational organization dedicated to the teaching of head and neck surgery to surgeons from all specialties. He is also currently the Organizing Chairman, Asian Conference on Oral and Maxillofacial Surgery, 2020 in Singapore. Dr. Wong will be speaking in our upcoming August 28th, 2019 3DHEALS Singapore Annual Event.
Jenny: When was the first encounter you had with 3D printing? What was that experience like?
Dr. Wong: I first tried 3D printing in 2008 when I had a case that needed a surgical cutting guide to be fabricated. At that time the place where I worked had bought the Z-Corp printer which essentially had powder base bound by an inkjet and then needed strengthening with cyanoacrylic glue. It didn’t find much use because there was no allocation for a technician and no one knew how to use it. So it became a white elephant and the powder kept on having to be discarded as it had expired. I found the process interesting but quite painful and realized that we needed trained personnel to do this. It was very difficult for busy clinicians to learn how to perform segmentation of the radiologic images, exporting in STL format and deciding on how to position the print on the platform. Essentially I did it by trial and error in between patients and after work with little guidance. That took me the better part of 2 weeks. The computer where we installed the segmentation software kept on hanging and running out of memory and had to be re-booted repeatedly. The first model I printed crumbled and I had to print it again taking 8 hours. The second model I managed to remove from the build chamber but part of it crumbled when I used an air-jet to remove excess powder as recommended by the manufacturer. Another 8 hours later, I managed to use the cyanoacrylic strengthener but my glove got stuck to the model and I managed to peel most of it out individually with a scalpel.
Jenny: What inspired you to start your journey in 3D printing ?
Dr. Wong: The recognition that we already had technological advances at hand but there was little implementation because, for many surgeons, it felt too difficult to learn or little impetus to change since the old methods worked. My argument against that is that there are always better ways to do things and the use of these technologies is not just fancy toys but you actually reduce the incidence of bad complications and improve the frequency of good outcomes.
Jenny: Who inspired you the most along this journey in 3D printing ?
Dr. Wong: The late Emeritus Professor Henk Tideman, University of Hong Kong, who was my Ph.D. supervisor-he made me realize that you need to keep up to date on the latest advances-he was much older than me but more in tune with technology than me. The second person who comes to mind is Prof Adrian Sugar of Morriston Hospital, Wales. He was, again, older than me but in the forefront of advanced digital technology for head and neck surgery.
Jenny: What motivates you the most for your work?
Dr. Wong: I am never content to accept the current way we do something is the best way. There are always ways to improve things.
Jenny: What do you think are the biggest challenge(s) in 3D Printing/bio-printing? What do you think the potential solution(s) is (are)?
Dr. Wong:
Challenges:
Lack of trained personnel
Lack of funding for equipment, training and employing such personnel
Solutions:
Having a centralized centre like that available in NUS (AM.NUS) is a possible way forward for institutions.
Jenny: What were/was the best investment you made in 3D printing?
Dr. Wong: Spending the time to learn how to clean radiologic images, performing segmentation, learning how to design with a CAD program and doing my own printing. It gave me a deep understanding of the nuances and intricacies involved.
Jenny: What was/is the biggest risk you took in your career?
Dr. Wong: Using 3D planning for surgery and printing surgical guides exclusively without any backup (in case the printed guides didn’t fit or work). I did the first orthognathic jaw surgery case in Singapore planned using computer virtual planning and then fabricate 3D printed guides in 2011. Prior to that, I had done a difficult post-traumatic deformity case in 2010 using a combination of 3D planning and 3D printed cutting and positioning guides for facial surgery.
Jenny: What is your favorite quote? Why?
Dr. Wong: I like this quote from Prof Ryan Bell- Everyone can have a bad day in the office. For surgeons, a bad day in the office implies a poor outcome for a patient with its own cost and morbidity. The use of digital technology improves good outcomes and increases the frequency of good outcomes.
This phrase means a lot because as surgeons, things that we do can impact a patient negatively. Not using the best tools at our disposal for treatment and even training is difficult to defend especially when such technologies are not exactly that new.
The lack of tissue regeneration in human beings, the deficiency of allogeneic transplants, and longer average life expectancy make the creation of functional tissues in the laboratory one of the most important problems of humanity right now. However, the results obtained are still less than desired since the tissue construct obtained must be functional for specific applications in regenerative medicine and advanced therapies.
Many new bioprinting groups have been created around the world in the past few years, and a variety of commercial systems are now available to the researchers. More and more publications on the matter are coming up. The results obtained are still far from true clinical application. For example, the organogenesis efforts well covered by the media, including the regeneration of the skin, cornea, or the heart are still too far away from human testing. In addition, a common misconception by the industry is that we directly create functional tissue to be used directly in clinical application; but in reality, we are bioprinting a scaffold loaded with cells. The key is to make these cells to behave as they do in ‘’in vivo conditions’’ and to promote the creation of functional tissues. This requires defining the right biofabrication strategy, but also the right maturation strategy.
For the creation of living tissue, both the bioprinting process and the maturation of the construct are crucial.
Thanks to the effort of tissue engineering technology and recreating in vivo conditions in the lab we can get results that open us the to the clinical application.
We try to keep it simple. In our research, we follow a 2-step approach to create functional tissues: 1) Bioprinted constructs (or scaffold) and under the right biofabrication strategy with the proper mechanical conditions. 2) In order to translate this matrix into functional tissue, it is necessary to use the method of accelerated maturation with the right stimuli (mechanical stress) in a special device.
We think that the best stress distribution is the key to success, and other approaches failed as they do not closely mimic the true physiologic conditions happening in nature.
To create specific functional living tissue, it is crucial that the bioprinting process and the ingredients selected such as the scaffold, the cells, and the bio inks (first step of the image) will promote the formation of the right tissue. What is equally important is the maturation procedure applied to the 3D cell-laden constructs (second block of the image). If we only think about bioprinting as a technology to recreate all the structure in the same form as shown in living tissue, we are going to fail. We must think of bioprinting as a way of creating cell-laden 3D constructs as a precursor of (but not final) functional tissue. The maturation and tissue formation process needs as much attention if not more than the bioprinting step. Focusing on the strategies related to both blocks in the diagram will be important to obtain the desired functional knee cartilage tissue, for example.
Literature search and real-life experience tell us that mechanical stress distribution is crucial as stimuli to create the right tissue. Unloaded muscle is absorbed, the unloaded bone loses its matrix. Also, the scaffold architecture will affect the stress distribution and other important parameters as the biodegradation occurs. This approach will open a wide research area for tissue engineers to develop protocols with different mechanical stress to create functional tissues, either using direct or indirect bioprinting methods. For example, using molds as temporal containers, a fiber structure holding loads and a cell-friendly matrix or scaffold, even adipose tissue containing blood vessels)
I predict that even more research and publication will happen in the coming years, making the generation of functional, vascularized, ready to be used tissues and organs a soon possibility.
(bioprinted scaffold seeded with human cells)
References:
1 Tissue Engineering and 3D Printing Platform (PITI3D), IDIPAZ, Hospital Universitario de La Paz, Madrid, Spain.
2 Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, Granada E-18100, Spain.
3 REGEMAT 3D S.L., Avenida de la innovación 1, 18100, Armilla, Granada, Spain.
Author’s Biography
José Manuel Baena is Ph.D. in Biomedicine from the University of Granada, Spain, MSc Engineering from Polytechnic University of Valencia, Spain and TU Braunschweig, Germany, and MSc from Oxford Brookes University, UK. He serves as scientific coordinator of the Tissue Engineering and 3D Printing Platform (PITI3D), IDIPAZ, Hospital Universitario de La Paz, Madrid, Spain and he is research associate in the group “Advanced therapies: differentiation, regeneration and cancer” IBIMER, CIBM, University of Granada, Spain. He has published several research papers and 1 book. He has presented his work in dozens of congresses around the globe. As a biotech entrepreneur, Baena founded BRECA Health Care, a pioneer in 3D printed custom made implants for orthopedic surgery, and REGEMAT 3D, a leader in the bioprinting industry. Expert in innovation, business development, and internationalization, lecturer in some business schools, he is passionate about biomedicine and technology.
The first Australian workshop on 3D bioprinting for tissue engineering and regenerative medicine was a huge success. Having only been organized a few weeks in advance, the Department of Biomedical Engineering at the University of Technology Sydney curated a fantastic, engaging and thought-provoking event with an attendance of over 100 people from leading local and international bioprinting companies, industry, academia and clinician representatives with widely regarded experts in the field. Dr. Carmine Gentile, having recently joined UTS from the University of Sydney himself with the help of Dr. José Manuel Baena of REGEMAT 3D put together a full-day workshop of technical talks, equipment demonstrations, and networking breaks. Bioprinting is a fast-evolving multidisciplinary field which has seen commendable strides in recent years, this is evident from the involvement and collaboration between materials & computer scientists, molecular & cell biologists to mechanical & chemical engineers alike. The potential for bioprinting applications in healthcare are endless, the distant goal being a reality where we can fabricate on-demand personalized tissues and organs in the operating room. To this day, however, advances inaccurate modeling platforms through the printing of spheroids in forming biomimetic organoids for research in drug discovery, toxicology screening and disease modeling have been made, all whilst simultaneously providing the potential to revolutionize the drug development process by improving the efficacy of clinical trials and decreasing the reliance of animal testing.
More than 100 attendees at the conference
The day started with an informative presentation from Dr. José Manuel Baena of REGEMAT 3D on the 3D printing of medical devices and the current bioprinting landscape. Globally, the bioprinting market is estimated to reach 4.7 billion by 2025 and the demand for customized systems to meet personalized solutions is already evident. José emphasizes the need for multidisciplinary collaborations worldwide to tackle these challenges head-on, and in doing so help translate this promising technology from lab bench to bedside.
Dr. José Manuel Baena of REGEMAT 3D
Next up, Dr. Cameron Ferris of Inventia Life Sciences discussed the paradigm shift from 2D to 3D cell cultures using digital bioprinting technologies and the importance of high throughput reproducibility tailored to the cell biologist’s user experience. Inventia was founded from the University of New South Wales so it was fantastic to see a number of their employees attend the event and interact with the audience. This was followed by a live video presentation from Ms. Da-Yae Lee of ROKIT Healthcare leading the debate on the economics and science of moving 3D bioprinting platforms to the operating theatre. Important commercialization frameworks, legislation, and regulatory hurdles were communicated in detail, providing up-to-date examples of projects and institutions already implementing this model including a recent milestone in India, PITI3D in Madrid, BioFab3D in Melbourne and opening in 2020 the Herston Biofabrication Institute between Metro North Health Service and the Queensland University of Technology. The last session before the morning break was given by application scientist Dr. Garry Bloomfield of CELLINK/Thermo Fisher Scientific talking about the portfolio of technologies for 3D bioprinting of tissues and organs currently available on the market including the recently released Lumen X by Volumetric and Holograph X by Prellis Biologics.
Dr. Cameron Ferris of Inventia Life Sciences
After the morning break, Prof. Maria Kavallaris of the Children’s Cancer Institute and the Australian Centre for Nanomedicine at UNSW, gave an eye-opening talk on 3D bioprinting of tumors for high-throughput applications. To characterize tumor-like properties of bioprinted spheroids, critical FACS analysis of hypoxic properties and cancer stem-like properties were compared between manual and bioprinted spheroids. Raising the question, can we produce bioprinted tumeroids from patient-specific tumors for HTP screening protocols? Next up, perhaps on everyone’s mind attending. What is ice printing? Prof. Tony Weiss from The University of Sydney presents a novel, reverse approach to tackling the challenges of vascularization in printed constructs. Highlighting that ineffective vascular perfusion limits the size and complexity of synthetic tissues and by utilizing sacrificial ice templates affords freeform fluid dynamics to ultimately shape and dictate complex branching hierarchal geometries. Addressing the primary considerations of functional vasculature being biocompatible and mechanically versatile, the use of tropoelastin coatings could enable small vessels to remain open.
A slide from Prof. Kavallaris presentation.
A slide from Prof. Tony Weiss
Before the
networking lunch and showcase for bioprinters, Dr. Carmine Gentile from UTS
gave a fantastic presentation on mending broken hearts with 3D bioprinted stem
cells. Carmine has extensive research experience in the field and was involved
in one of the first research groups even to conceptualize the notion of organ
printing thereby delivering an in depth talk on the interface between
developmental biology, engineering and biomaterials involved in bioprinting for
the heart with a focusing on tissue spheroids as building blocks.
Dr. Carmine Gentile
After the break, Prof. Gordon Wallace from The University of Wollongong needs no introduction, with a wealth of research experience, Gordon talked about the convergence of the why? When? And where? of printing with living cells. The key takeaway being the complexity and lengthy considerations required at each stage of the developmental process before reaching the fabrication stage. Dr. Khoon Lim from the University of Otago put forward the potentials of light-activated bioinks for 3D biofabrication using digital light processing techniques. Whilst, Prof. Joanne Tipper from UTS talked about 3D in vitro models for spinal cord injury. A Prof. Majid Warkiani having recently been awarded the young tall poppy science award by the Australian Institute of Policy and Science for his work on non-invasive cancer diagnostics discussed how his group implements 3D micro-engineered systems for cancer drug screening.
Prof. Gordon Wallace
Bioprinter from Inventia Life Sciences
About the Author:
William Harley graduated with honors in medical biotechnology from the University of New South Wales. Currently, he is undertaking a Ph.D. at the University of Melbourne in acoustophoretic bioprinting. Stemming from his research experience in biomaterials, stem cells, and nanofabrication, he is driven by the clinical translation of personalized regenerative medicine. He is passionate about the innovation of 3D printing in healthcare and is determined to orchestrate a series of 3D HEALS events to engage in the Australian community.
3D printing is a spectacular technology, there’s no doubt about this.
The amount of new applications and solutions in various industries is impressive, but perhaps the new applications in healthcare are the ones that most impact and give us light on how the future of medicine could be.
In Santiago of Chile, two innovative companies have developed a unique project in the world.
3D Printed toys made with Copper3D anti-bacterial materials
Copper3D Inc., the company that develops new antimicrobial materials for 3D printing, has partnered with the company Toylisto, uses its platform to turn 2D images of drawing into 3D printable designs called “Art Toys”.
Combining these two technologies, Copper3D and ToyListo have developed a project to create “Antimicrobial Art Toys”, a beautiful project that seeks to collaborate with the emotional well-being and recovery of children with complex illnesses and immunosuppression who are in clinical isolation and for this reason have no access to play with conventional toys, which by their characteristics (porous polymers and complex geometries) harbor a high bacterial burden that can be very dangerous for these children.
The pediatric Hospital Dr. Luis Calvo Mackenna was chosen by these companies to pilot this innovative project, initially in the Oncology Unit with children in clinical isolation, who from now on can create their own drawings and see them turned into real toys for them to play safely within the isolation units.
Immunosuppressed children can create their own drawings and see them turned into real toys for them to play safely within the isolation units.
Regarding this project, Esteban Ruiz-Tagle, founder of the company Toylisto, mentions the following:
“This project was born with the objective that we have as a company to do something really different and of social impact. Hence, in some conversations with Daniel Martínez from Copper3D about combining the technologies of both companies, the idea made sense immediately. We did some tests and went to Dr. Luis Calvo Mackenna Children’s Hospital to offer our services with the antibacterial material of Copper3D. After several meetings, we obtained the approval to become suppliers in an unprecedented service all over the world: to turn children’s drawings into collection figures, safe for children with complex diseases that have them with immunosuppression. But none of this would have been possible without the antibacterial characteristics of the PLACTIVE® material and the security provided by all the studies, certifications and approvals that have.
Finally, what we are most happy about is that for the first time, children who have had to abandon pets, teddies and toys because of their health risk, will now be able to dream, play and have fun safely with the “Art Toys” by Toylisto”
This project, in addition to having the unique component of the creativity of these children transformed into a 3D printed collection figure, has another very innovative element. The figure that each of these children receives is made with the new antimicrobial materials developed by the company Copper3D.
These new antimicrobial materials (or “active nanocomposites” as they are called in Copper3D) are revolutionizing the biomedical 3D printing industry and have even come to be tested by NASA for the 3D printing of medical devices on the International Space Station (ISS).
Daniel Martínez, CINO, and co-founder of Copper3D mentions in this regard:
“For us, this project has been a path full of learning and has allowed us to fully comply with the main purpose of our company: Utilize innovation and cutting-edge technology to improve the quality of life of people. This is exactly what we have done in this project with Toylisto, to use cutting edge technology in 3D design and new antimicrobial materials to allow these children in clinical isolation to play with unique figures, designed by themselves and manufactured with a clean, safe and certified material.
This is just one more example of the impact that Antimicrobial 3D Printing can have and it poses a very promising future in the use of this technology for other applications and solutions in the Biomedical world, but also in other industries such as Aerospace, Food, Animal Care, and Mass Consumption products.
We are also proud that the prestigious Luis Calvo Mackenna Children’s Hospital has trusted our companies to pilot this project, that we plan to extend to other hospitals in Chile and, through our international networks, to other pediatric hospitals in the USA, Europe, South Africa, South East Asia, and the Middle East.”
Related to this project, Dr. Jorge Lastra, Director of the Dr. Luis Calvo Mackenna Hospital comments the following:
“For our hospital, it is a pride to be a benchmark in innovation and to be able to incorporate these new technologies that have already been tested and validated internationally, in the treatment and well-being of our children, especially in those that are in more complex conditions such as immunosuppression and clinical isolation.
We hope with this initiative to mark an important milestone and to be able to show the world that from Chile, with creativity and technology, great projects of global impact can be made and that they also have a positive impact on the quality of life of our children.”
Toylisto and Copper3D wanted to produce and donate 100 #AntimicrobialArtToys this year for the children of this hospital.
Claudo Soto MD (Medical Director Copper3D), Esteban Ruiz-Tagle (Founder Toylisto), Daniel Martínez (CINO Copper3D) and Javier, 8-year-old patient on Oncology Unit Hospital Calvo Mackenna.
About the Author:
Daniel Martínezis a Chilean Healthcare professional passionate about innovation and the impact it can have on the quality of life of people. His professional career has been linked to management and marketing in healthcare organizations. In 2008 he obtained an MBA in Chile.
Then, in 2016 he started an MSc. of Innovation, which led to a profound change in his way of seeing the world.
He began to see global problems as big challenges and opportunities to generate a huge impact with creative, innovative, and disruptive solutions. A typical day of Daniel consists of a mix between academia (he is professor of innovation in several universities in Chile) and his activities as Chief Innovation Officer at Copper3D, where he is responsible for the short term (commercial and marketing strategy) and the long term of the company working on brand positioning, new products for the portfolio, innovation architecture, new business models and strategic alliances.
There’s no question that computer modeling, simulation, and additive manufacturing have transformed clinical medicine around the world. What’s always fascinated me, though, is the variety of ways these technologies have been implemented in different hospitals and even different departments within the same hospital. As a prototyping fellow at Sinai BioDesign, a design and prototyping group within the Mount Sinai Hospital in New York, I’ve seen firsthand almost all of the ways both 3D printing and scanning can be leveraged within a health system. Like many other tools and data streams, there’s no single way 3D medical data is acquired or used within the health system. In each case, though, these printing, scanning, and rendering applications are crucial to clinical care and research. Last week, in part 1 of this Expert Corner blog, I focused on use cases for 3D modeling and printing. For part 2 this I’ll be discussing clinical applications of 3D scanning technologies, the other side of the medical 3D coin.
Unlike medical modeling – the 3D rendering of
anatomy (oftentimes patient-specific anatomy) – 3D scanning always resides in
the digital domain. Nevertheless, there are numerous different technologies
employed to capture 3D scan data, each with its own set of pros and cons that,
much like the various life cycles of anatomical data covered in last week’s
Expert Corner, have utility to different clinical practices. To begin with, it
is worth noting the three major groups of 3D scanning technologies: LIDAR,
textured light, and photogrammetry.
LIDAR
Figure 1. An example of LIDAR scanning from Faro, a manufacturer of scanners, showing Jay Leno getting his face scanned by a hand-operated laser scanner, as well as the resulting 3D surface (inset)
LIDAR stands for Light Detection And Ranging
and is essentially radar or sonar but with infrared light as the signal source
instead of radio waves or sound waves. A scan is acquired by rastering an
infrared laser light source over an object, capturing its contours and
textures. Either the scanning source or the object being scanned must be
spatially fixed, though, in order to establish a fiducial reference and
coordinate system by which the cloud of 3D points can be plotted as the scan is
taken. Together, these points are interpolated to form the surfaces of the
scanned object. Depending on the scanning hardware being used, the resolution
of LIDAR scanning ranges from several millimeters to a few microns. It’s also
worth noting that LIDAR scanning is line-of-sight (LoS), meaning anything the
light source can’t reach can’t be scanned. Sometimes a workaround can be
achieved by changing the positioning of the scanner or the subject. The highest
resolution LIDAR scanners are often employed during the quality assurance
portion of the medical device development process to ensure manufacturing is
within required tolerances. At lower resolutions, LIDAR scanning is sometimes
used to capture complex surfaces of the human body, such as the face.
Textured
Light
Figure 2. An example of textured light scanning, showing a pattern projected onto an object and the resulting 3D cloud of points reproduced through the algorithmic analysis of the distortion of the pattern (courtesy 3ders.org)
Textured light scanning works by projecting a
series of different sized grids, either in the visible or infrared spectrum,
onto the surface of an object. A camera linked to the projection system detects
the projected grid and the distortions to the pattern made by the object being
scanned are recorded. Based on how the pattern is distorted, an algorithm
extrapolates the surface of the object, rendering it in 3D. Like LIDAR
scanning, either the scanning unit or the object can be rotated to capture all
angles since this scanning approach is also LoS. Textured light is typically
regarded as the second-highest resolution 3D scanning technology, after LIDAR.
The ultimate determinant of textured light scanning resolution is the
combination of the resolution of the projected grid and the resolution of the
camera detecting the grid – usually on the order of a millimeter.
It’s also worth pointing out that, for both LIDAR and textured light scanning, there are many materials that are “un-scannable” because of their interaction with the visible or infrared light being employed in the scanning process. Many metallic objects are extremely difficult to scan with LIDAR or textured light because of the way their surface reflects the incident scanning light. In these cases, a temporary matte coating can be applied to improve the optical properties of the material.
Photogrammetry
I often tell people that if there’s a method
of 3D scanning that they’ve seen before, it’s photogrammetry. This approach
captures a 3D rendering of an object by taking 2D pictures from multiple
positions, either by using one camera and capturing one angle at a time, or
more commonly through the use of large camera arrays. Photogrammetry is
particularly appealing in many fields because (at least in the case of
multi-camera arrays) it is an extremely quick method of 3D scanning. In a
360-degree photogrammetry array – on the order of 80 cameras oriented around a
platform at many different angles – it takes only as long as it takes to snap a
picture to capture a 3D scan. Compare this to LIDAR and textured light, which
can take several minutes at their fastest.
Figure 4. An example of a photogrammetry scan with (left) and without (right) the 2D texture mapped to the 3D surface. While some features, such as the eyebrow are still relatively easy to distinguish, details around the eye become much harder to pinpoint.
As is often the case, though, the advantages
of photogrammetry come with tradeoffs. Chief among them is the poor resolution
of the technique. This often comes as a surprise to many because, at first
glance, the 3D models rendered appear very detailed. This detail, though, does
not reflect the geometry of the 3D object produced through the scanning
technique but rather reflects the 2D texture of the scanned object mapped
to a low-resolution. It is this 2D texture – comprised of the individual images
of several dozen cameras, often DSLRs – that creates the illusion of a 2D
model. Remove that texture (as would be the case for any single-color method of
3D printing) and all your left with is a blob generally shaped like the object
you were scanning. Don’t get me wrong, there are certainly times where the geometry
captured by photogrammetry is sufficient for the end application of the 3D
model, and some geometries capture better than others (think about what a
person with their arms raised might look like, versus someone with their arms
crossed), but on the whole, this method has a resolution on the order of
centimeters, or worse.
Clinical
Applications
Figure 5. The Fit3D scanner and an example of the resulting scan (source: Fit3D)
So why did I go to all that effort to explain
these three major groups of scanning technologies? Because different ones are
employed by different clinical fields, and for different reasons. At Mount
Sinai alone, two or more of these 3D scanning technologies are being used
almost daily.
The first example I’d light to highlight is the Fit3D scanner used by Sinai’s Institute for Next Generation Healthcare. This device is part scanner, part scale, and uses a LIDAR scanner and rotating platform to measure a patient’s weight, body fat percentage, and water content, among other metrics (similar to any other high-tech digital scale today) while also capturing a full-body 3D scan. The end result, on the scanning side, is a marble statue-like rendering of the subject, which can subsequently be measured according to metrics like waist-to-hip ratio, height/waist circumference, and other emerging metrics that look at physiological health beyond BMI. For these measurements, a reasonably high-fidelity 3D reproduction of the patient is important, in order to derive accurate measurements from the 3D scan. The texture of the subject (e.g., the color/pattern of their shirt) has no bearing on these metrics. As such, the LIDAR scanning approach is far superior to photogrammetry for the data it provides, even though the scanning process takes about a minute to complete, versus a few seconds.
On the other hand, the lab of Dr. Ethylin
Jabs, in Mount Siai’s Genetics Department, uses a scanning system called 3dMD,
which uses photogrammetry techniques to capture the faces of patients. Many
genetic conditions manifest in the form of facial asymmetries and
malformations, which can be captured by the scanning system and subsequently
detected by clinicians reading the scans.
Figure 6. The 3dMD photogrammetry scanner (courtesy: 3dMD)
Given what I’ve just explained about the
various scanning technologies, though, you might be wondering why the Jabs lab
uses photogrammetry when this is the lowest resolution form of scanning. The
situation only becomes more perplexing when you see that the 3dMD system is a
fairly large, elaborate system that’s not very easy to move. Couldn’t a LIDAR
or textured light technique capture a better rendering of the face? While the
answer to that question is “yes”, it doesn’t fully capture the method in which
these scans are being used. It turns out, as I found out several years ago when
I showed some different LIDAR and texture light scanners to Dr. Jabs, that
there are some very good reasons why her lab uses photogrammetry to capture
these 3D scans. First and foremost, many of her patients are infants – a group
of people infamous for their inability to hold still. While it might
technically be possible to use LIDAR or textured light to capture a scan of an
infant, it’s certainly a much longer process than the 1-2 seconds it takes to
snap a photo. Photogrammetry lets Dr. Jabs’ team see and process the data for
many more patients than any other scanning technique would. Second, the facial
metrics being extracted from these scans rely on the accurate identification of
facial features (e.g., the outside corners of the eyes), which are rendered
much more clearly through the 3D-mapped textured captured by photogrammetry.
Thus, even if there is some inaccuracy incurred due to the lower spatial
resolution, it’s more than made up for by the precision with which clinicians
can identify facial features when extracting anatomical measurements to
correlate with genetic data.
Conclusions
Be it 3D printing or 3D scanning, the adoption
of 3D visualization and fabrication techniques in hospitals has been
transformative in the delivery of patient care and the expansion of
personalized medicine. By digitizing and systematizing this information, it has
become possible to better prepare for surgery, improve the detection of genetic
defects, and even improve the accuracy of measurements as basic as height and
weight. We’re still a little ways off from everyone getting a full 3D scan
workup as part of their yearly physical, but I think these examples and the
spread of scanning technology overall show that we’re well on our way.
About the Author:
Joseph Borrello is currently a biomedical engineer and Ph.D. Candidate at Mount Sinai, working in the labs of Drs. Kevin Costa and Junqian Xu, in addition to managing digital fabrication operations within the Sinai BioDesign innovation team. Previously, he worked at 3D Systems on technical development in the consumer marketing department and as a liaison with engineering project management teams.
He received his bachelors in Biomedical Engineering from Macaulay Honors College at The City
College of New York, where I remain active in the Zahn Innovation
Center, an on-campus tech startup incubator.
Joseph is also an active member of the New York City startup ecosystem. He is the founder of Proto-Sauce, which is developing new materials for resin-based 3D printing, as well as the CTO of Biosapien, leveraging 3D printing to produce personalized therapeutics. He also tries to summarize as many of the local happenings as he can in his newsletter Magnitude and Direction.
Finally, Joseph is also the editorial assistant for 3DHEALS Lattice newsletter, where he tirelessly curate the best content for healthcare 3D printing and bioprinting community with the 3DHEALS team.
The standard process for cellular agriculture, also known as lab-grown meat or clean meat, is to sample some cells from the desired animal, culture them, assemble them on a scaffold, and grow the cells in industrial volumes. Similar processes have been developed to produce artificial insulin and rennet with the aid of engineered microbes.
The sampling and culturing of cells have been standard practice in research and biopharma for years. Previous conferences discussed the steps to take when the original cells are cows and pigs rather than human and cancer. This year those considerations were understood to be feasible. The next hurdle, as many hopeful start-up unicorns know, is scaling up. That is where bioreactors come in. The big question at this point in the industry is: how can we grow enough of these cells to make a difference in the market, at a price that is competitive, with sustainable and ethical materials?
Every New Harvest conference starts with the New Harvest Fellows presenting their research for the community. Santiago Campuzano from the University of Ottawa showed how his lab has been decellularizing celery to use as scaffolding for cell growth. Next Scott Allan of the University of Bath went over different types of bioreactors their pros and cons. Tufts researcher
Natalie Rubio brought a different perspective by discussing the potential of invertebrate cells for bio fabricated food.
Would people be willing to eat protein derived from bugs?
Additional sponsored research was displayed in the poster area.
After a coffee break, the presentations turned from the lab to the marketplace. Geraldine Paulus gave an overview of the history and mission of the Engine, a venture fund started by MIT to address tough problems with long solution timelines. While the Engine doesn’t currently have any cellular agriculture companies in their portfolio, the industry’s location at the intersection of medicine and agriculture makes it a natural fit for the Engine’s approach to investing. Deb Arceolo presented about her experiences creating transparency at the Hershey Company and what those lessons could mean for getting the public comfortable with lab-grown meat. Last year’s New Harvest Conference had similar presentations about lessons that could be learned from the roll-out of GMO foods, showing that the story is as important to success as the science.
After lunch, the next series of speakers focused on the engineering hurdles of cellular agriculture. Will Patrick, Culture Biosciences, brought the power of cloud computing to the next generation of automated, high-throughput bioreactors as service. Continuing the theme of automation,
Nick Legendre from New Age Meats presented an eye-opening talk on the parameters required for cultured meat production and how they can only truly be optimized in combination, not isolation. Automation and machine learning allow researchers to test many protocol variations in a short period of time. Nina Buffi from OSPIN shared an analysis of bioreactors from an economic perspective, comparing types of bioreactors and the business model associated with each one.
After another coffee break, it was time to turn the conversation to the particulars of culturing seafood. Lou Cooperhouse of BlueNalu gave an overview of the why and how of cellular aquaculture, followed by local Tim Sullivan from the Gloucester Marine Genomics Institute talking about how his organization is bringing biotechnology to fisheries and Marlin Keith Cox of Seafood Analytics did a deep dive into the data that can be measured in muscle tissue.
That was a long day, so the conference turned more informal with an open mic, group photo, and happy hour.
The second day of the conference started bright and early with Meera Zassenhaus speaking briefly about Community Engagement at New Harvest. Since cellular agriculture is a new industry, laws are having a hard time keeping up with the science. Brian Sylvester, Special Counsel at Foley & Lardner LLP, Rohini Bansksota, Director Of Policy At Finless Foods, and Eric Schulze, VP of Product and Regulation at Memphis Meats, shared the stage to discuss the regulatory landscape, which has been especially active over the last year.
Another panel followed after coffee with speakers sharing their experiences with cellular agriculture around the globe. Podcast host Alex Shirazi presented an overview of cellular agriculture hotspots. Singapore was represented by Ka Yi Ling of Shiok Meats, which was in the news recently for their public tasting of dumplings with lab-grown shrimp meat. The Netherlands was represented by Jonathan Breemhaar, Lead Automation Engineer at Mosa Meats, creator of the famous hamburger that started the second wave of cellular agriculture (more on that later). Nick Beaumont from Heuros spoke about the cellular agriculture-related opportunities in Australia, and Shir Friedman, Head Of Communications At SuperMeat, shared that Israel is a particularly beneficial location in which to launch an alternative food company, of which it has more per capita than any other country in the world. Lisa Feria, CEO at Stray Dog Capital, moderated.
Another break, this time for lunch, brought together a third panel discussing careers in cellular agriculture. David Bowman from Mission Barns, Jun Axup from IndieBio, Justin Kolbeck from Wild Type, Kate Krueger from New Harvest and moderator Meera Zassenhaus shared their individual circuitous paths to their current roles and explained what types of skills and experiences cellular agriculture companies are hiring for. Surprisingly, it’s not all science and research. As cellular agriculture grows as an industry and gets closer to interacting with the public the way traditional food companies do, there is a growing need to people who can bridge the conversation between the lab, the production floor, and the business world.
The day ended with a turn to the social sciences. Garrett Broad of Fordham University shared lessons from the academic world of communications studies on how to build trust with the public. Step one: assume the relationship will be a dialogue, not just a one-way flow of information from the expert to the uninformed. Step two: take people’s concerns seriously.
The final presentation was with Neil Stephens from Brunel University London, who has been studying the cultured meat community since 2008. He has tracked the fascinating change in narrative from academic to start-ups, from in vitro meat to lab meat to clean meat to cellular agriculture. He shared that the unveiling of the Mosa Meat burger in 2013 was a game-changer in the community, solidifying the narrative around cellular agriculture as a sustainable, ethical technology aimed at meat-eaters.
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