3D Printing and Bioprinting For Cancer Care – Guide

Cancer, what a modern-day existential threat to humanity, a word that triggers a cringe from the most fearless. Over the past decades in modern medicine, we have made much progress in cancer care, ranging from diagnosis, surgical advancements, to therapeutics. Despite that, cancer is surpassing heart diseases as a leading cause of death in the United States in 2020. [Ref] The demand for faster diagnostics and better treatment is 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.

What Non-bio 3D printing and 3D Bioprinting Share

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

While this blog could be split into two parts, i.e. non-bio 3D printing and 3D bioprinting, it was not. A 3D printed anatomical model for presurgical planning using polymer share several common features with 3D bioprinting a tumor model for cancer drug development. These features directly stem from several fundamentally new, unique, and powerful characteristics additive manufacturing offers.

Digital manufacturing:

(Ideally) 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.

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.

Rapid prototyping:

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

Complexity for free:

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

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

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

Oncological Care using Non-Bio 3D printing  

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-specific treatment guides for surgery and for radiation therapy to achieve improved surgical outcomes.  As the technology matures, there are more and more published creative uses of this type of 3D printing. Some of the main applications include [4]:

Pre-surgical planning.

With a copy of the patient’s disease in hand, the surgeon can more effectively strategize 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.  

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.

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.

Post-resection patient-specific implants.

Space-filling patient-specific prosthetics are increasingly in demand in post-resection patients.

Simulation models for radiation therapy planning.

A key treatment option in cancer patients is radiation therapy. 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]

Oncological Care using 3D-Bioprinting  

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.

Disease modeling.  

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 win 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, as well as animal models, have been developed for cancer treatment research. While animal models are often more superior to cell cultures, they are expensive in cost and time, and results from the 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 principals 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 over animal models.

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

Tumor microenvironment simulation.

It’s been long recognized that the proliferation of cancer depends not just on cancerous cells alone, but 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]  

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]

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 for 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. Bioprinted 3D tumor models have been shown to be more effective in modeling treatment response than 2D models. [2]

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 combination and dosage of cancer treatments will maximize effectiveness while minimizing side effects.

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, was made as to 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 cost. 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 when 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]

3d bioprinting for cancer--Microfluidic chip designed for detecting sepsis. Photo Credit: Janet Sinn-Hanlon and Technologynetworks.com [Ref: 8]
Microfluidic chip designed for detecting sepsis. Photo Credit:  Janet Sinn-Hanlon and Technologynetworks.com [Ref: 8]

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.

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

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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.

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