Dec 29, 2019 Time flies.
We have had a great 2019, with increasingly more innovations, merger and acquisition activities, partnerships, new startups, and regulatory breakthroughs in the past 12 months. In 2019, 3DHEALS has shared at least 560 pieces of external news and publications through our social media channels in addition to our own 50+ Expert Corner and Community Activities articles. Of these, I have picked what I believe to be 9 game-changing news and trends, that deserve everyone’s attention for the near future.
Here they are:
1. Artificial Intelligence and 3D printing
What happens when two powerful technologies work together? This year, we devoted two Expert Corner blogs focusing on how AI/ML can accelerate 3D printing applications. “When artificial intelligence meets 3D printing” is a general overview of the problems and solutions. A few weeks later, a second blog dives deeper into how can AI/ML optimize the SLA printing process. Many companies are working on leveraging AI/ML technology to gain an upper hand, either in terms of workflow or products, including but not limited to Autodesk, Sculpteo, GE Additive, Align Technology, MedicalIP, and Axial3D.
2. Mixed Reality and 3D Printing
In 2018, when Dr. Jessie Courtier presented Sira Medical (Previously known as HoloSurg3D), an AR/VR startup he co-founded during 3DHEALS2018, a 3D printing conference, the direct connection between AR/VR/mixed reality is clearly demonstrated. At the beginning of 2019, he made the technical connection between the two technologies from advanced visualization perspective in an Expert Corner blog. However, surgeons and interventionists (rather than diagnostic radiologists) perhaps are the most avid supporter and innovators of advanced visualization technologies, as they are in a much greater need of real-time imaging guidance, either with a mixed reality product or a 3D printed model. They are often the driving force behind innovations using both, and a growing number of publications and startups are appearing in this space, using mixed reality and 3D printing in a complementary fashion for a variety of applications.
3. Point of Care (POC) Additive Manufacturing
Two models have emerged. In a model adapted by Lima Corporate and Hospital for Special Surgery, the device manufacturer creates a close-by the facility to produce on-demand complex implants needed by the hospital. In a similar fashion, Stryker teamed up with multiple organizations in Australia for a project called “Just in time implants”, where on-demand patient-specific implants can be produced for the patient after bone tumor resection. In the second model, hospitals or healthcare providers act as device manufacturers and create facilities within the premise of the hospitals or clinics. For example, popular software and hardware companies like Materialise, Formlabs, Ultimaker, Stratasys, and HP have worked together in creating a workflow for POC 3D printed anatomical models (Mimics InPrint Certification Program). On the implant side, POC manufacturing solution is also available through startups such as Kumovis and Apium, both manufacturing POC 3D printers that can manufacture PEEK implants. The regulatory landscape of the second model is yet to be defined.
4. Reimbursement for 3D Printed Anatomical Models
Imagine that your doctor has fewer surprises when he/she looks into your body during surgery.
Few people have doubts that 3D printing for surgical planning, either 3D printed anatomical models or surgical guides, is beneficial to the patients. Many institutions and individuals have invested millions in creating a 3D printing service in the hospital or clinic, yet the work is currently largely unpaid. The journey to reimbursement for 3D printing for anatomical models and surgical guides has proven to be a challenging one. However, On November 1st, 2018, it was announced that “the American Medical Association (AMA) CPT® Editorial Panel accepted at its September meeting a Category III code proposal led by the American College of Radiology (ACR) for 3D anatomic modeling. The new Category III codes will be effective on July 1, 2019.” 3DHEALS devoted two blogs, one by Robert Wesley, and the other myself focusing on what getting CPT Category III code means. In short, Category III is considered temporary and does not guarantee reimbursement (nor does Category I, but it moves closer to Medicare reimbursement). The Radiological Society of North America (RSNA) and the American College of Radiology (ACR) plan to establish a new medical 3D printing clinical data registry to collect 3D printing data by the end of this year, aiming to eventually achieve Category I status. Again, CPT Category I code does not mean reimbursement is for sure, but a lot more certain than Category III code. Getting paid in a complex healthcare system depends not only on codes but also on other overlapping existing codes, the overall payment environment, and pricing strategy.
5. Bioprinting Vasculature
Bioprinting made it to the cover of Science twice this year. One is by a group at Rice University (Houston, Texas), led by Bagrat Grigoryan, PhD and Professor Jordan Miller, now co-founders of Volumetric Biotechnologies (Reference: Science 03 May 2019: Vol. 364, Issue 6439, pp. 458-464 DOI: 10.1126/science.aav9750) and the other by a group at Carnegie Mellon University, led by Professor Adam Feinberg, now a co-founder of Fluidform (which we will discuss next) (Reference: Science 02 Aug 2019: Vol. 365, Issue 6452, pp. 482-487 DOI: 10.1126/science.aav9051) (Disclaimer: Both startups were invited to Pitch3D earlier this year and I am an investor in Volumetric Bio.)
The study from Rice University demonstrated that “that projection stereolithography can be utilized with water-based photoactive bio-inks containing live cells to result in intricate perusable 3D architectures unprecedented within hydrogels.”
In the abstract of the article, the scientists wrote, “Solid organs transport fluids through distinct vascular networks that are biophysically and biochemically entangled, creating complex three-dimensional (3D) transport regimes that have remained difficult to produce and study. We establish intravascular and multivascular design freedoms with photopolymerizable hydrogels by using food dye additives as biocompatible yet potent photoabsorbers for projection stereolithography. We demonstrate monolithic transparent hydrogels, produced in minutes, comprising efficient intravascular 3D fluid mixers and functional bicuspid valves. We further elaborate entangled vascular networks from space-filling mathematical topologies and explore the oxygenation and flow of human red blood cells during tidal ventilation and distension of a proximate airway. In addition, we deploy structured biodegradable hydrogel carriers in a rodent model of chronic liver injury to highlight the potential translational utility of this materials innovation.”
The results of this study could mean a giant step forward in producing implantable vascularized human tissue, and also at a speed that was not possible previously in the bio-fabrication world.
6. FRESH Technique Makes A Debut to the Public
Only a few months later, Science published another article (see reference above) focusing on bio fabrication using collagen to create heart components at various scales (from valve to capillaries) using the FRESH technique (a.k.a. freeform reversible embedding of suspended hydrogels) from a group at Carnegie Mellon University.
In the abstract of the published article, the scientists wrote, “ Control of pH-driven gelation provides 20-micrometer filament resolution, a porous microstructure that enables rapid cellular infiltration and micro vascularization, and mechanical strength for fabrication and perfusion of multiscale vasculature and tri-leaflet valves. We found that FRESH 3D-bioprinted hearts accurately reproduce the patient-specific anatomical structure as determined by micro-computed tomography. Cardiac ventricles printed with human cardiomyocytes showed synchronized contractions, directional action potential propagation, and wall thickening up to 14% during peak systole.”
The resolution, mechanical property, and the end applications represent a milestone of biofabrication and that bioprinting is finally one step closer to dreams of many, including personalized implants using soft materials previously not possible.
7. Generative Design and Topology Optimization
For many decades, many healthcare applications using 3D printing aim to reproduce what we know about our anatomies because nature’s design has proven to be the most effective in healing. However, with the advancement of computer sciences, more design software innovations are now showing us that perhaps that’s not the case. That is, when it comes to bioengineering, a complete replica may not be necessary and maybe even inferior to what we can design using tools with features of generative design and topology optimization. In fact, the publication from Rice University mentioned above collaborated with a design group, Nervous System, and used a generative design method to create a bioprinted lung alveolar. 3DHEALS has been fascinated with the subject lately and published two blogs on the subject, one by our Boston 3DHEALS community manager Jordan Pelovitz, also a designer himself, and myself. Personally, I would invest in the next generative design software startup for healthcare in a heartbeat.
8. FDA On Regulating 3D-Printed Medical Products
(Reference: Science Translational Medicine 03 Oct 2018: Vol. 10, Issue 461, eaan6521 DOI: 10.1126/scitranslmed.aan6521)
Although it was published in October 2018, this paper is such a rare and important publication by the core 3D printing team at FDA. If you have not read it, read it today before the year ends! This paper, however, does not include discussions focusing on class I devices, anatomical modeling, and 3D printing drugs.
There are several reasons why this paper is important:
- It did the research for the industry based on hard-to-obtain past 510(k) cleared AM medical devices based on FDA’s internal database between Jan 2000 to April 2016. The data was presented in a clear fashion, with a well-defined methodology.
- Knowing the past trends can help with the future, either from risk or opportunity perspectives. This is especially important to entrepreneurs and investors.
- The agency provides many resources to directly engage with its constituents. We are posting these resources below as well for easy access. For companies based on emerging technologies such as AM, it is crucial to start the conversations early and in an intelligent fashion (we will have a post on this later), and consistently. It is a relationship worth building.
- Finally, there are clearly a lot more uncertainties in terms of regulation biologic 3D printing (or biofabrication, bioprinting). However, this is on FDA’s radar now, and it is foreseeable something more substantial will materialize in the coming year 2020.
Reposting: Resources available to stakeholders regarding 3D printing and interacting with the FDA.
- 3D Printing of Medical Devices: https://www.fda.gov/3dprinting
- Technical Considerations for Additive Manufactured Devices: Guidance for Industry and FDA Staff: https://www.fda.gov/downloads/medicaldevices/deviceregulationsandguidance/guidancedocuments/UCM499809.pdf
- Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products: Guidance for Industry: https://www.fda.gov/downloads/Drugs/
- GuidanceComplianceRegulatoryInformation/Guidances/UCM590547.pdf
- Types of Communication During the Review of Medical Device Submissions: Guidance for Industry and FDA Staff: https://www.fda.gov/downloads/medicaldevices/deviceregulationsandguidance/guidancedocuments/UCM341948.pdf
- Center for Devices and Radiological Health (CDRH) Learn: https://www.fda.gov/training/cdrhlearn/
- Office of Tissues and Advanced Therapies (OTAT) Learn: https://www.fda.gov/biologicsbloodvaccines/newsevents/ucm232821.htm
- CDRH’s Division of Industry and Consumer Education (DICE): email: DICE@fda.hhs.gov
- Center for Biologics Evaluation and Research (CBER)’s Manufacturer’s Assistance and Technical Training Branch (MATTB): email: industry.biologics@fda.gov
- Manufacturer and User Facility Device Experience (MAUDE): https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/search.cfm
9. Volumetric 3D printing
We are hearing more and more about this new 3D printing technique, which is actually redefining the term “3D printing” and “additive manufacturing”, as it is no longer an additive process of layer-by-layer manufacturing but an additive process that occurs in three dimensions simultaneously. Volumetric 3D printing is pretty precise. An analogy of this printing advancement is equivalent to the adaption of (three dimensional) computed tomography from traditional (two dimensional) x-ray in medical imaging. In fact, the researchers at UC Berkeley and Lawrence Livermore National Laboratory were inspired by how CT scanners work and reverse-engineered the process of digital design to the precise light patterns that will cause gelation of specific photosensitive resin. Although the technology is still rudimentary, it does appear to have the potential of 100x the manufacturing speed, reducing material waste, and even improve resolution to achieve many needs in generating complex elastomer structures and structures conducible to biofabrication processes, both very valuable to the medical community. The year 2020 will surely be an exciting one.
Conclusion:
There were so many exciting happenings in 2019 in this what we call “niche” territory, from technological advancements to business arrangements. We are surely appreciative to all the experts who have contributed to the Expert Corner blog and looking forward to more in 2020. The future is bright, but it will continue to take a village (or “Tribe”) to stay up to date and continue to engage and learn from each other in the 3DHEALS community. Feel free to always contact me directly on news and tips worth sharing with our Tribe.
Happy New Year!
Related Articles:
Cancer: What 3D Printing (Bioprinting) Can do For Oncological Care
Bioprint Heart Components: Fluidform3D CEO Mike Graffeo
Engineering Vasculatures: Interview w/ Dr. Jordan Miller
Interview: Jon Rowley, Founder & Chief Product Officer, RoosterBio
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