Engineering the Future of Medicine: New Applications of 3D Tissue Bioprinting

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As a species, we are master engineers who have created machines that have completely changed our way of life. We build skyscrapers that peak through the clouds, computers that fit in our pockets and electric cars that go from zero to sixty at a ludicrous speed. And yet, the most precise and well-articulated systems remain those built by nature. The human body is an example of a perfect organic machine that does, from time to time, require replacement parts.

The quest for artificial tissues and organs remains a slow and uphill battle that can be boiled down to the fact that tissues and organs are incredibly complex. Possessing many different compartments that communicate with each other, intricate microarchitecture, and multiple cell types with the need of a continuous nutrient supply. Though master mechanics we may be, we’ve yet to discover the methods to engineer our own bodies.

3D bioprinting has arose as a possible solution to this problem by making it easy to design and engineer life. 3D bioprinters and bioinks are used by researchers worldwide to ensure that we humans master the field of biological engineering to eradicate diseases and replace broken parts.

This technology is laying the groundwork to aide in our search for the holy grail of the artificial, personalized organ.

So what is bioprinting?

It involves recreating the 3D structure of a tissue using a fabrication technique wherein a computer program builds a structure layer-by-layer using biocompatible materials (or bioinks) and cells. These bioinks are designed to mimic the architecture of the extracellular matrix in which cells are suspended to aid in their specific differentiation. Additionally, cells themselves can be incorporated into these constructs.

It should come as no surprise that geometry matters within biology. Signaling pathways activated in 2D are very different from 3D and cells on a petri dish do not accurately represent features and functionality of the human body. It’s time we added another dimension to the study of biology.

You can start imagining building a complex organ step-by-step using the 3D images, such as those from MRI and CT scans, native cells from a patient, and biologically compatible materials. This technology is still in its nascense and is currently only used in research settings but we are beginning to see the exciting early developments that will lead to life changing clinical applications.

How is bioprinting technology used today?

Create Custom Bone and Cartilage Grafts

How many of us have titanium hips and screws in our joints? By understanding the specific defect size, through either MRI or CT, and combining 3D bioprinting with the correct, advanced biomaterial, a surgeon will one day make a 3D printed structure in the shape of the patient’s bone void and implant that structure, resulting in repaired and regenerated, natural bone personalized to each patient. This will prove to have tremendous therapeutic benefit over traditional methods that either don’t provide regeneration or can’t be personalized.

Dr. Rajapakse’s Lab University of Pennsylvania used the Allevi 2 bioprinter to print a nasal septal cartilage scaffold that precisely matched patient’s nasal defect, in both size and shape. Dr. Rajapakse stated in his publication, “Nasal septal perforations (NSPs) are relatively common. They can be problematic for both patients and head and neck reconstructive surgeons who attempt to repair them. Often, this repair is made using an interpositional graft sandwiched between bilateral mucoperichondrial advancement flaps. The ideal graft is nasal septal cartilage. However, many patients with NSP lack sufficient septal cartilage to harvest. Harvesting other sources of autologous cartilage grafts, such as auricular cartilage, adds morbidity to the surgical case and results in a graft that lacks the ideal qualities required to repair the nasal septum. Tissue engineering has allowed for new reconstructive protocols to be developed.”

Dr. Rajapakse uses a patients’ CT scans and converts them into a file that the Allevi 2 bioprinter could read and reconstruct. This allows him to customize the construct to match the patient’s nasal septal defect exactly. This is an amazing first step in the goal to create patient-specific tissue grafts that could be deployed for myriad tissue types.

Regenerate Cardiac, Nerve and Muscle Tissue

The Nervous System, a highway of electrical communications, regulates all aspects of our physiology, from movement to thoughts by having electricity chemically run across conductive tissue. That is why conductivity is a key integration in the materials used for engineering tissues.

We look to our community of material scientists to help develop the new standards in bioinks. One such example is our partnership with Dimension Inx LLC to offer a cutting edge new bioink on our platform – 3D Graphene 3D-Paint. This novel material provides users the ability to integrate conductivity into electroactive tissues, such as skeletal and cardiac muscle, peripheral and central nerve, and biomedical devices. This electrically conductive material is one of a kind and a breakthrough in tissue engineering. While it is conductive, it also is cytocompatibile and integrates with ease into living tissue.

Nearly all tissues operate via electrical signaling to some degree; but the biggest one, in addition to both peripheral and central nerves, is muscle (including cardiac muscle). Electrical conductivity as a biomaterial property is highly desirable and necessary in tissue engineering… The problem is that traditional electrically conductive materials, like metals, do not integrate well with soft tissues in the body. Bioprinted 3D-Graphene is different and its ability to be customized within the specific tissue opens up a world of clinical applications.

Test Drugs Outside the Body

In 2012 Dr. Dongeun Huh and Dr. Donal Ingber’s paper in Science Translational Medicine successfully created a diseased lung-on-a-chip. Their findings demonstrated the ability to identify a drug’s life-threatening toxicity that went unnoticed through traditional experimental methods, such as animal testing models. It was a milestone achievement, but since then organ-on-a-chip manufacturing has mostly remained unchanged. Conventional methods gave you little freedom to easily customize and create inner-chip architectures for your experimental models until now. Allevi bioprinters allow researchers to create custom architectures within organ-on-a-chip devices for disease modeling and drug testing.

Dr. Yu Shrike Zhang of MIT uses an Allevi Bioprinter to model thrombosis in his lab. Thrombosis (or blood-clotting) constitutes a major reason for morbidity and mortality in cardiovascular diseases and its complications. Dr. Zhang uses his Allevi bioprinter to create in-vitro thrombosis models. By printing a 3D hydrogel with microchannels running through the chip, he was able to perfuse the microchannels with endothelial cells to render them biologically active. After creating the vein, he was able to infused the channel with coagulated blood to form biomimetic thrombosis models that reproduce the physiology of thrombosis in vivo.

This remarkable application means that Dr. Zhang is now able to study thrombosis in his lab on repeatable and customizable human models. By being able to model and study the body outside the body, researchers are speeding up the rate of discovery and are able to create novel therapies and drugs faster and cheaper than ever before.

Customized organ-on-a-chip designs will play a major role in the innovation of tissue engineering and pharmaceutical development. This unique high impact application for biofabrication will not only change the field today, but the healthcare industry tomorrow.

What is the future of bioprinting?

With over a 120,000 people in the US alone on waiting lists for organs and others experiencing chronic problems due to the long-term damaging effects of post-transplant immunosuppression, we are throwing everything we can at this problem.

As a community of scientists, we’ve already succeeded in bringing together multidisciplinary teams of researchers, physicians, and engineers to take on the biggest challenges to human health such as cancer, AIDS, and now organ regeneration. Here at Allevi, we empower you to build with life to fundamentally change the way science and patient care is performed.

We imagine a future of truly personalized medicine where we can eliminate the organ waiting list, create custom grafts and cure disease. There is no question that bioprinting will change the course of medicine forever and finally turn biology into an engineering discipline that we can master. We invite you to join the revolution.

About The Author

Madeline Winter
COO | Allevi
(formerly BioBots)

Madeline Winter is the chief operating officer for Allevi and is responsible for sales, marketing, and daily business operations. Her background in mechanical engineering provides her with a data-driven and detailed approach to problem-solving. She is responsible for ensuring strategic vision translates into profitable operations. Ms. Winter’s efforts have helped grow Allevi from a company of a few users to a leader in biofabrication worldwide.