Guide: 3D Printing For Cancer Care

Cancer, what a modern-day existential threat to humanity, is a word that triggers a cringe from the most fearless. I don’t need to give you a precise mortality/morbidity number, because chances are high that you have already encountered cancer directly or indirectly if you are reading this article. Over the past decades in the field of oncology, we have made significant progress, from diagnosis, and surgical interventions, to therapeutics. According to a recent report from McKinsey, “In 1970, of those diagnosed with cancer in the United States, approximately half would have been alive five years later. For those diagnosed in 2009, the figure was closer to 70 percent.”   Despite that, cancer is still surpassing heart disease as a leading cause of death in the United States in 2020. [10] The demand for faster and more accurate diagnostics, and less invasive and personalized treatments (precision medicine) are driving researchers to technologies like 3D printing and 3D bioprinting. This guide aims to summarize ongoing developments and progress made using 3D printing and 3D Bioprinting for cancer care. We will periodically update this guide to stay up to date. Please email info@3dheals.com if you want to recommend new technologies or companies for us to be included in future versions of this guide. 

Here is an outline for this guide: 

It would be erroneous to try to apply 3D printing or 3D bioprinting without paying attention to the overall trends in cancer care. While the main therapeutic options in the field of oncology are still surgical resection, chemotherapy, radiation therapy, and hormonal therapy, newer treatment options are becoming more impactful. These include but are not limited to the following [9, 11]: 

  • Digital health – This includes telehealth, wearable devices, apps, and other digital tools to allow providers and patients to engage remotely, cutting costs, providing convenience, and preventing complications.
  • Precision medicine – Current cancer treatments often come with significant morbidities because they often kill healthy tissues along with cancer cells. There is an increasing consensus that personalized cancer care with improved early diagnosis including genetic testing (i.e. pharmacogenomics), less and more customized chemotherapy, more immunotherapy, and even gene therapy.
  •  Competitive landscape – The oncology market is extremely competitive. With more disruptors in the space (gene therapies, immunotherapies, etc), and expiring patents, drug companies are racing to control costs and decrease drug development timelines. According to our recent virtual event on the subject, only 5% of all cancer drugs eventually benefit patients after a long and expensive R&D period, with an average development timeline of 9.5 years. Even after launch, only a small number of these will have sufficiently transformative benefit-to-risk profiles to drive return on investment.
  • Market Growth – The field of oncology will continue to expand at a rapid pace due to a large aging population. In the U.S., it is estimated that more than seventy percent of cancer diagnoses with occur among adults over 65 years old. This is a 45% increase from 2010. Oncology costs will rise by 9-12% annually through 2023, with global oncology costs exceeding $240 billion [9,12]. Therefore, cost control is a priority no matter where you live. Even as new and better therapies emerge, pharma companies can expect to face mounting pressure to reduce treatment costs.
  • Accelerated Innovation –  According to the McKinsey report, ‘though it took about eight years between the first therapy for HER2-positive patients in 1999 and the next therapy, the gap between the first-to-market PARP inhibitor in 2013 and the next was less than two years.” This is not only manifested in scientific advances but also in an uptick in venture capital investments and acquisition premiums.  

With these trends in mind, let’s see how 3D printing and bioprinting can transform future cancer care.

What benefits does 3D printing (biologic and nonbiologic) bring to the table for cancer care? 

3d bioprinting for cancer: 3DHEALS2018 3D Printed Anatomical Models by AnatomicsRx
3D Print Credit: 3DHEALS2018 3D Printed Anatomical Models by AnatomicsRx

While they are very different, a 3D printed anatomical model for presurgical planning using polymer shares several common concepts with a 3D-bioprinted model for cancer drug development. These features directly stem from several fundamentally new, unique, and powerful characteristics additive manufacturing offers.

1. Digital manufacturing:

Complete control over the manufacturing process, starting from design to the end product. Digitalization enables automation, and automation enables scaling that no existing conventional manufacturers or laboratories can provide.

2. Mass customization:

No two patients are identical, and the call for personalized medicine in oncological care simply cannot be met using conventional manufacturing processes to the degree 3D printing can achieve.

3. Rapid prototyping:

While there is a general trend toward promoting “mass production” using AM technologies, “rapid prototyping” remains to be a dominant reason for adaption in healthcare.

4. Complexity for “free”:

3D Printing and bioprinting offer complexity in end-product simply cannot be found elsewhere in the manufacturing world. Whether a one-off 3D-printed anatomical model for complex life-saving surgery or a uniquely designed complex microfluidic chip, both pose some of the most economic applications using 3D printing.

Additionally, significant overlap exists between non-organic 3D printing and bioprinting:

  • Many different 3D printing technologies can be used for both, including extrusion-based 3D printing (e.g. FDM, SLA, inkjet-based, etc.)
  • Materials and Bio-ink play a critical role in the final product.

How are people using non-biologic 3D printing in cancer care? 

3d bioprinting for cancer: 3DHEALS2018. 3D Printed presurgical planning model of a mandibular tumor. 3D printed by WhiteCloud
Photo: 3DHEALS2018. 3D Printed presurgical planning model of a mandibular tumor. 3D printed by WhiteCloud

Many applications using 3D printing for oncological surgical intervention are similar to applications in non-oncological surgeries. Being the “digital twin” of the tumor before the patient undergoes surgery, these applications leverage the visual and haptic advantages of a 3D-printed model and create patient-

Many applications of 3D printing for oncological surgical intervention are similar to applications in non-oncological surgeries. Being the “digital twin” of the tumor before the patient undergoes surgery, these applications leverage the visual and haptic advantages of a 3D-printed patient-specific model. Complimentary devices also include surgical guides for preoperative planning, testing, intraoperative precision cutting, device placements, and postoperative radiation therapy planning devices to achieve improved clinical outcomes. As technology matures, there are more and more published creative uses of this type of 3D printing. For those who are interested in more details on how to implement additive manufacturing from an operational management perspective, we have put together a very in-depth regularly updated guide.

We also have quite a few on-demand videos on 3D printing in hospitals. 

Some of the main applications include [4]:

1. Pre-surgical planning.

With a patient-specific 3D model in hand, the surgeon can more effectively strategize the surgical approach, and even practice on the 3D-printed model, reducing intra-operative decision-making and complications. This is especially important for high-stake, complex procedures, where the tumor involves critical structures, such as important vessels and nerves. It is foreseeable that three-dimensional printing will be more widely incorporated into virtual surgical planning in less complex surgeries as the technologies are more affordable and user-friendly. 

2. Patient and physician communication tool.

A picture is worth a thousand words. A 3D-printed model is worth likely more. The combination of spatial-visual and haptic information conveyed through a 3D-printed model not only helps physician-physician communication, but also physician-patient communication, removing information barriers that often waste time and effort in trying to reach consensus. This is particularly helpful in pediatric cases and uncommon pathologies. The communication benefits were cited in a number of publications but also well-discussed in our webinars focusing on point-of-care 3D printing. [13] 

3. Intra-operative surgical guides.

3D printed patient-specific surgical guides are becoming more and more popular in surgery in general, as it reduces intra-operative decision making, provides consistent surgical outcomes, and reduce operating time. Many ongoing clinical trials currently focus on the immediate and long-term outcomes using these surgical guides. 

4. Patient-specific prosthetics and implants.

Space-filling patient-specific prosthetics and implants are increasingly in demand in post-resection cancer surgery patients. This is, in particular, relevant for breast cancer surgery, reconstructive surgery, and orthopedic surgery in a variety of disfiguring procedures. There are still many technical challenges. These include highly heterogenous cancer types (For example, there are many different types of breast cancers involving different cell types and having different molecular/genetic profiles),  a lack of 3D printing material options, labor intensive and expensive printing process, a general lack of clinical trials outcome data, and invalidated implant mechanical properties.

However, what is encouraging is that there are a number of non-biologic 3D printing implant startups are already tackling cancer surgeries facing millions of patients each year. These include and are not limited to Onkons Surgical (musculoskeletal cancer), Prayasta (breast cancer), Lattice Medical (breast cancer), BellaSeno (breast cancer, chest wall defect, musculoskeletal defects). 

5. Patient-specific radiation oncology.

A main adjuvant treatment in cancer care is radiotherapy, aiming to stop the spread of metastasis because oftentimes, surgery alone cannot effectively remove all the cancer cells. The residual tumor can invade adjacent tissues, but also spread quickly to the rest of the human body via a process called metastasis.  This is an active area of research because radiation comes with many side effects.

Patient-specific 3D-printed simulation models can potentially reduce the side effects of radiation therapy, preserving the function of normal tissue adjacent to the tumor. [6] There are already quite a lot of innovations in creating patient-specific brachytherapy for a variety of cancers, and we have several Expert Corner blogs on this subject:

3D Printing of Customizable Phantoms in Radiation Oncology

3D Printing for Cancer Treatment – Radiation Therapy Liver Phantom

Some of the notable development include 3D Systems announcing VSP® Bolus to optimize radiotherapy targeting in April 2022. 

Quite a few startups are also moving into the space, including 3DLifePrint and Adaptiiv

How are people using 3D bioprinting in cancer care? 

3d bioprinting for cancer--Modular Design of Microfluid Chips. Photo Credit: Reza Amin et al. 3D-printed microfluidic devices. 2016 Biofabrication 8 022001
Modular Design of Microfluid Chips. Photo Credit: Reza Amin et al. 3D-printed microfluidic devices. 2016 Biofabrication 8 022001

Bioprinting is tackling three main aspects of cancer treatment: disease modeling, diagnosis, and drug delivery. Microfluidics, some considered a subcategory of bioprinting, play a growing and instrumental role in cancer management. While not all microfluidics are 3D printed, many latest innovations use 3D printing as an alternative manufacturing method or use 3D printing in conjunction with end applications. Therefore, microfluidics is included in this part of the discussion. Microfluidics currently has a much larger market than bioprinting, and maybe even tissue engineering. For those who are interested, we have a dedicated on-demand course on microfluidics and also an upcoming live event.

Disease modeling.  

breast cancer bioprinting modeling
Raphael Lichtnecker from Puredyne ViscoTec presenting his perspective on bioprinting breast cancer model

In Sun Tzu’s famous “The Art of War”, he wrote “If you know the enemy and know yourself, you need not fear the result of a hundred battles. If you know yourself but not the enemy, for every victory gained you will also suffer a defeat. If you know neither the enemy nor yourself, you will succumb in every battle.”

Effective disease modeling is the key to winning the war against cancer. The creation of a high-fidelity cancer model enables more effective personalized treatment strategies and the discovery of new oncological medicine. In the past, planar (2D) and 3D cell cultures and animal models, have been developed for cancer treatment research. While animal models are often superior to cell cultures, they are expensive in cost and time, and perhaps more importantly, increasingly ethically unaccepted by several major regulatory entities.

It is also important to mention that a major drive toward non-animal disease models including 3D cell culture, bioprinted 3D tissue models, and microfluidics-based technology comes from the governments.

Recent regulatory milestones need your attention

2013: EU bans cosmetic animal testing [14]

After two-decade-long efforts in the EU, in 2013, EU Directive 76/768/EEC (Cosmetics Directive) established “a testing ban i.e. it is prohibited to test a finished cosmetic product and its ingredients on animals in the EU; and a marketing ban i.e. it is prohibited to market a finished cosmetic product or its ingredients in the EU if they are tested on animals.” 

“Between 2007 and 2011 the EU spent €238 million on funding non-animal replacement tests – a testament to its concern about animal welfare, the 3Rs, and the quest to find alternative methods.”

Needless to say, this explains why some of the earliest commercialized bioprinting products focuses on the skin. We have a guide focusing on bioprinting skin for those who are interested. 

2021: EMA implements new measures to minimize animal testing during drug development. [15]

In 2021, European Medicine Agency pushes forward continuous efforts against animal testing in the pharmaceutical industry. “The Agency promotes three principles — replace, reduce and refine; commonly referred to as 3Rs — through EMA’s Innovation Task Force (ITF). This action will facilitate the development and implementation of New Approach Methodologies (NAMs) that are in line with the European Union legislation on the protection of animals used for scientific purposes.” Alternative approaches to animal models mentioned included tests based on human and animal cells, organoids, organ-on-chips, and in silico modeling.

2021: The congress passes FDA Modernization Act of 2021. [16]

Introduced in House (04/15/2021), this bill amends the Federal Food, Drug, and Cosmetic Act to allow manufacturers and sponsors of a drug to use alternative testing methods to animal testing to investigate the safety and effectiveness of a drug, and for other purposes. The regulatory landscape is clarifying

More arguments against animal testing

Additionally, results from animal models often cannot be translated into human subjects.

This likely explains why 95% of all cancer drugs in development cannot reach the market. [1] Recently, 3D bioprinting-based cancer models using human cells are gaining popularity over traditional 2D and 3D cancer cell cultures made using other tissue engineering techniques. The main reasons are again related to the main principles behind additive manufacturing mentioned at the beginning of the article. The reduced cost and increased complexity in the bio-printed cancer models can be a more cost-effective (and ethical) solution than animal models.

The Big Question: Is Bioprinted 3D Tissue Model Better than Existing Models? 

The answer is Maybe. 

More importantly, will the 3D model behave more like real cancer?

The verdict is out there according to our panel on this subject lately. However, we are likely to see a lot of data on this comparison in the next six to twelve months. So stay tuned for our next update. 

While emerging technologies tell a great story, many disappoint in reality. While grifters always exist in every industry, the majority of the scientists and entrepreneurs are honest and truly believed in what they are working on. However, scientific and technological advancements take both time and luck, and often, it depends on the state of understanding of the disease process. The process may not always be linear, either. Many discoveries started with an observation, then decades of the unraveling of the science behind it, followed by hypothesis, testing, and eventually the creation of useful therapeutics for the patients.

During our recent virtual event focusing on 3D bioprinting cancer,  Dr. Antti Arjonen, Chief Science Officer at Brinter, presented how he is translating our observation and understanding of breast cancer pathogenesis into creating useful bioprinted cancer models. One simple reason why 3D bioprinted cancer models are superior to 2D models can be extracted from the fact that cancer occurs often first in the breast ducts than lobules. Having a disease model that can recreate more accurate cell-cell interaction, cell-extracellular matrix (ECM) interaction, and tumor micro-environment (high pressure, hypoxia) in a consistent high-throughput/low-cost manner will be more useful. 

That said, just like a simple imitation of a bird’s wings cannot allow one to fly, it is only when we understood Bernoulli’s principal and fundamental physics behind aviation, could the Wright brothers invented the first motor-operated airplanes and the giant industry today after a century of evolution. Maybe the bioprinted ear cannot actually hear, but using regenerative medicine to replace or repair our body parts that no longer work is what the world wants. 

Some key developments in bio-printed cancer models include the following [1-3]:

Cancer Disease Model:

1. Tumor microenvironment simulation.

It’s been long recognized that the proliferation of cancer depends not just on cancerous cells alone, but on interactions between cancer cells and many other players in the “microenvironment”, which is a combination of the extracellular matrix, immune cells, vascular cells, chemical cues (growth factors and cytokines), and biophysical cues (interstitial pressure and matrix mechanics), and more. [1,3] 3D Bioprinting can more precisely. create a scaffold of this microenvironment. While most bioprinted cancer models are created using the extrusion-based technique, which typically is of lower resolution, higher resolution structures using two-photon laser bioprinting technology can be as high as less than 500 nanometers according to CEO of VoxCell BioInnovation Karolina Valente. Even for more conventional extrusion-based bioprinting , innovations are improving the technology. For example, very recently, Raphael Lichtnecker from Puredyne ViscoTec presented a new tool using a progressive cavity pump for better-controlled extrusion type bioprinting. 

2. Tumor angiogenesis.  

Both sacrificial and direct bioprinting can create cancer models with vascularization. [1] A 3D printed microfluidic chip, which is a small chip with complex channels and valves, can be produced to mimic complex tumor vascularization. [3,5] To date, there has been no effective anti-metastasis medication. Understanding the disease process will be a key step. Bio-printed models have been shown to illuminate the process of breast cancer. [1]

During our recent virtual event focusing on cancer, Dr. Karolina Valente from VoxCell has showcased ways her company is tackling cancer vascularization challenge from several angles, using innovative software simulation, bioinks, and laser based printing technology. 

VoxCell
Dr. Karolina Valente from VoxCell BioInnovation presents her version of the vascularization model for cancer research

3. Metastasis model.

To date, there has been no effective anti-metastasis medication. Understanding the disease process will be a key step. Bio-printed models have been shown to illuminate the process of breast cancer. [1]

Drug discovery.

Effective disease modeling results in a better understanding of cancer pathogenesis, which results in the discovery of new anti-cancer drugs. Some experts have indicated that bioprinted 3D tumor models are more effective in modeling treatment response than 2D models. [2] While the verdict is still out there, a drug discovery platform that is highly reproducible, more accurate, and more capable of automation will likely generate better outcomes than the incumbent process. This will not only translate into more money saved but more importantly, more new and effective therapeutics for an evolving world. 

Drug screening for patient-specific care.

Parallel to drug discovery is drug screening for drug resistance and toxicity, often using patient-derived cancer cells. [2] Since cancer drugs are often toxic, patient-specific combinations and dosages of cancer treatments will maximize effectiveness while minimizing side effects. Given the current trends in oncological treatments stated earlier, a patient specific cancer model will be congruent with the overarching reference of pharmacogenetic approach in future cancer care.   

Diagnosis and Drug Delivery. [5,7,8]

Also, parallel to the development of bioprinting technologies is the advancement of manufacturing microfluidic chips, often called “organ-on-a-chip”, or “lab-on-a-chip”. Compared to traditional manufacturing techniques, bioprinting offers a cheaper solution with all the added value of 3D printing as described above. [5]

Diagnostic tool.

Microfluidic chips acting as a point-of-care diagnostic tool are not new, in fact, were made as the core technology in the infamous biotechnology startup Theranos. As a diagnostic tool, the microfluid chip offers a solution that requires less sample volume, faster turnaround time, and potentially lower test costs. Leveraging nanotechnologies/nanomedicine. There is a growing ecosystem surrounding this application, focusing on diagnosing cancer cells from early metastasis to sepsis. [7,8]

Drug delivery system.  

In the author’s opinion, there is no accident around any major breakthrough or discovery in medicine. With the concurrent advancements in immunology, genetics, nanotechnologies, and nanomedicine, it is only a matter of time before a more personalized targeted drug delivery system will appear. In fact, researchers are already proposing targeted treatment using microfluidic chips designed to destroy metastatic tumor cells. [7]

Which Non-biologic 3D printing companies are focusing on cancer care? 

Like any emerging technology, it is often a trial and error process in finding the best market product fit. We actively curate a list of companies, private and public, that use 3D printing as a core technology in their products and services. You can find the latest companies using our Company Directory, under the search term “cancer”.  Here is an infographic we recently shared including these companies, excluding bioprinting companies (see the following section): 


Which bioprinting companies are focusing on cancer care? 

You can find the latest companies using our Company Directory, under the search term “cancer”. Here is an infographic we recently shared including bioprinting companies and microfluidics companies that use 3D printing as a core technology.

Conclusion:

Like many other emerging technologies, 3D printing is a powerful tool that can transform healthcare and provide solutions that we could not imagine yesterday. It is important to understand the fundamental advantages of the technology to best utilize them in solving problems, and it is also important to always keep an open mind to learn and leverage technological advancements from adjacent fields. One step at a time, the battle against cancer will be won with these exciting technological advancements.

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Raphael Lichtnecker from Puredyne ViscoTec presents new tool for better controlled extrusion type bioprinting.

References:

  1. Tingting Liu, Clement Delavaux, Yu Shrike Zhang, 3D bioprinting for oncology applications, J. 3D Print.Med. (2019) 3(2), 55–58
  2. Aishwarya Satpathy, Pallab Datta, Yang Wu, Bugra Ayan, Ertugrul Bayram & Ibrahim T. Ozbolat (2018). Developments with 3D bioprinting for novel drug discovery, Expert Opinion on Drug Discovery, 13:12, 1115-1129,DOI: 10.1080/17460441.2018.1542427
  3. Yu Shrike Zhang, Margaux Duchamp, Rahmi Oklu, Leif W. Ellisen, Robert Langer, and Ali Khademhosseini. Bioprinting the Cancer Microenvironment. ACS Biomaterials Science & Engineering 2016 2 (10), 1710-1721. DOI: 10.1021/acsbiomaterials.6b00246
  4. Georgia Makin, The current landscape of 3D printing in oncological surgical interventions Future Oncol. (2019) 15(26), 2999–3002
  5.  Reza Amin et al. 3D-printed microfluidic devices. 2016 Biofabrication 8 022001
  6. 3D Printing for Cancer Treatment – Radiation Therapy Liver Phantom
  7. Alena Gribko, et al.  Is small smarter? Nanomaterial-based detection and elimination of circulating tumor cells: current knowledge and perspectives. Int J Nanomedicine. 2019; 14: 4187–4209.
  8. The Growing Role of Microfluidics in Point-of-Care Diagnostics
  9. Emerging Oncology Trends: 2021 And Beyond
  10. Cancer to surpass heart disease as leading cause of death in US by 2020
  11. Delivering innovation: 2020 oncology market outlook
  12. Age and Cancer Risk
  13. The use of 3D-printed models in patient communication: a scoping review

Want to write a piece for 3DHEALS Expert Corner? Email us: info@3dheals.com

About The Author:

jenny chen

Jenny Chen, MD, is currently the Founder and CEO of 3DHEALS, a company focusing on education and investing in the space of bioprinting, regenerative medicine, healthcare applications using 3D printing. She is trained as a neuroradiologist. With a focus on health technology, Dr. Chen also serves as a startup Mentor to IndieBio EU and French Tech Hub, tech accelerators that help IT and life science companies launch and expand their product offerings, identify customers, and manage operations. Her interests lie in the applications of emerging technologies (especially in the field of 3D printing and bioprinting), automated biology, and has a vision of a decentralized and personalized healthcare delivery system for our near future.

3D Bioprinting Cancer (On-Demand, 5/5/22)

Bioprinting Vasculatures (On-Demand, 3/24/22)

3D Printing for Cancer Treatment – Radiation Therapy Liver Phantom

Manufacturing of Functional Tissues In Vitro Using Bioprinting and Bioreactors

Vahid Serpooshan: Repairing Heart with Tissue Engineering

Enabling Futuristic Bioelectronics With Bioprinting: Beyond the Obvious

3D Printing for the Human Organ Shortage: Putting Bio back into Bioprinting

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