Innovations in 3D Bioprinting

Summarized from the article: Recent advances in personalized 3D bioprinted tissue models by Jonathan P. Walters‑Shumka et. al.

By: Lili Hostetler

Introduction

Drug development is key factor for progressing the field of medicine. While animal models are commonly used for drug development, they do not have the same biology as a human patient, are plagued by high failure rates when transitioning to human studies, and harbor many ethical concerns.

3D bioprinting can be used to create new models for drug testing and regenerative medicine. In 3D bioprinting living cells are deposited layer-by-layer, allowing for the creation of 3D models that can mimic human tissue more accurately than existing 2D models. 3D models allow more complex cell-cell interactions than typical 2D models, in turn, allowing for better transport of nutrients, oxygen, and drugs through the structure.

3D bioprinting utilizes specialized 3D bioprinters and bioink. Bioinks are composed of hydrogels, that, like a typical 3D printer, can be used to print desired structures according to a computer-aided design (CAD) file.

A schematic of a 3D bioprinter

Another important component to creating better biological models using 3D bioprinting are stem cells. Stem cells are cells that can be differentiated into any type of cell in the human body. This means they have a lot of potential for applications such as drug discovery, disease research, and regenerative medicine.

Innovations - Cancer

1.9 million new cases and 600,000 deaths due to cancer occur every year in the United StatesIt is the result of mutations in DNA that cause uncontrolled cell replication and growth. The development of cancer is dependent on both genetic and environmental factors.

While there are a wide variety of treatments available for cancer, it is difficult to determine a one-size-fits-all treatment for different cases, as each patient may react differently depending on their genetics. 3D bioprinting can create a personalized model of cancer, based on the patient’s own cells. For example, various studies have created 3D bioprinted models of an individual patient’s cancer (such as bile duct cancer or skin cancer) to determine how well that specific patient may response to anticancer drugs. Doctors can then use this information to prescribe new treatments to their patients.

Innovations - Heart Disease

523 million people are affected by heart disease which causes 19 million deaths per year worldwide. Accurate models of the heart are essential for cardiovascular drug development. This includes the ability of heart tissue to conduct electricity to allow for the rhythmic pumping of the heart. One research group used stem cells to print cardiac microtissues that could beat spontaneously and rhythmically.

Additionally, 3D printed heart tissue could be implanted into patients, reducing the demand for already limited donor hearts. One such condition this could be used for is myocardial infarctions which can result in scar tissue forming within the heart. 3D bioprinted cardiac tissue could be implanted at this site, giving healthy heart cells a scaffold to grow on and reducing the risk of scar tissue formation. This approach could also eliminate the need for immunosuppressants, as the printed heart tissue would be composed of the patient’s own cells, reducing the risk of rejection.

Innovations - Skin

Skin is the largest organ of the human body and is responsible for protecting the body from disease and injury. The skin has multiple layers, each with a slightly different composition and structure that help to fulfill its function. Despite its remarkable regenerative capabilities, large-scale injuries such as extensive burns and deep lesions remain a major challenge for regenerative medicine. Most methods for repairing these injuries rely on skin grafts from the patient, or transplants from deceased donors, which may be difficult to obtain depending on the extent of the injury.

3D bioprinting can create a multi-layered skin graft, capable of reproducing the various differentiated layers of the skin. This could be further enhanced by incorporating stem cells, as stem cells have demonstrated the ability to differentiate into various skin types including important structures such as hair follicles and sweat glands.

One study by Albouy et. al used a 3D bioprinted robot on a pig to directly deposit skin-based bioink on the surface of a lesion layer by layer, demonstrating how 3D bioprinted skin could be deposited onto a patient.

Pig Surgery

Innovations - Nervous Tissue

Nervous tissue such as that found in the spinal cord or brain is extremely difficult to model due to its complex architecture. Bioprinted nervous tissue with the soft, flexible mechanical properties of brain tissue often fail under their own weight. One solution to this limitation is the use of sacrificial materials. These are peeled away from the main structure and disposed of after printing, similar to scaffold structures used in typical 3D printing.

An example of supports generated for a typical 3D Printer

One model, which used a scaffold to support the neural tissue throughout printing, was able to print a white matter model that mimics the site of a spinal cord injury.

Limitations and Conclusion

The biggest hurdle to overcome for 3D bioprinted structures is the ability to integrate with the vascular and nervous systems, to allow for adequate blood flow and sensation through these implanted tissues. However, there is great need for personalized 3D tissue models that can mimic an individual patient’s genetics and specific disease phenotype both in the fields of drug development and regenerative medicine. With further research and development, 3D bioprinting could hold the key to better understanding of complex disease structures, thus advancing drug development and tissue engineering leading to better treatments and better health outcomes.

For more information: https://link.springer.com/article/10.1557/s43577-023-00551-2