3D Printed Cells Could Mend A Broken Heart

Khalifa University of Science and Technology Researchers Developing 3D Printing Technologies to Create Optimized Soft Tissues for Implantation into Human Hearts

human heart
MSc student Maryam Aljassim loads commercial bioinks into a commercial 3D bioprinter.

Soft tissues created with advanced 3D printers in the UAE may soon help mend heart valves, heart vessels, and heart muscles in patients suffering from cardiovascular disease. Researchers from the Khalifa University of Science and Technology’s Department of Biomedical Engineering are developing a range of innovative 3D printing and tissue engineering technologies to create functional, patient-specific soft tissue implants that replace native tissues.

Their aim is to optimize conditions in 3D printed tissues to ensure that the chemical, mechanical and electrical communications that normally take place between cells within tissues, a process known as ‘cross-talk,’ is functioning as in healthy human bodies.

“We do not regard the cells as mysterious ‘black boxes’, as others in the field of 3D bioprinting tend to do. We are making an effort to understand the basic science behind the cell types we are interested in, and then leveraging 3D printing to provide the final product,” explained Dr. Jeremy Choon Meng Teo, Assistant Professor.

Dr. Teo is part of the University’s 3D bioprint team, which includes Biomedical Engineering Department Chair and Professor Dr. Tim McGloughlin and Associate Professor Dr. Cesare Stefanini. The team has been leading the University’s tissue engineering research since 2012 in an attempt to create living, functional, 3D printed vascular and muscle tissues that can be customized and implanted in patients suffering from cardiovascular disease — the leading cause of death in the UAE.

To achieve this, they are conducting a series of research projects that span across a wide range of fields in biomedical engineering, from in-depth studies on how to reprogram cells called fibroblasts into vascular tissue cells, to the development of 3D bioprinters and optimized cell-specific ‘bio-inks’.

3D Bioprinters: Printing Living Tissues

Humans have been trying to replace diseased and damaged tissues using man-made materials for centuries, but these materials have limitations and are often not physiologically similar to native tissues. Now, thanks to rapid technological advances in the field of tissue engineering and personalized regenerative medicine, coupled with the advent of 3D bioprinting, scientists are getting much closer to growing functional, customized tissues and organs in an economically feasible way.

A 3D bioprinter leverages the versatility of 3D printing – which is an additive manufacturing process – to build customized living tissues and organs by carefully layering patterns of cell-containing bio-inks into a desired shape, like a heart valve or blood vessels. According to a recent report by business intelligence provider Visiongain, the 3D printing market for healthcare applications is predicted to surpass US$4 billion by 2018.

As part of the University’s biomedical engineering research, a team of Emirati students developed a custom 3D bioprinter, which earned them an Innovation Award earlier this year. The printer is capable of 3D printing with the team’s customized bio-inks and forming tissue structures without the need of stiff support structures, and thereby reducing time and cost.

Getting Soft Tissues Right with Optimized Bio-ink

Engineers have become very capable at bioprinting bone tissues in the lab, as the ink used to print a functional bone tissue is made of hard, polymer materials that have properties ideal for bone cells.

But soft tissues continue to pose challenges for biomedical engineers, in particular due to their lack of regenerative capacity and commonly soft jelly-like structures; a texture that is difficult to achieve through bioprinting.

“Bones have an excellent regeneration capacity, and fusion between lab-built bone tissues and natural bone tissues has been successful. On the other hand, soft tissues are more complex. They do not regenerate easily and are more sensitive to their surrounding environments. Thus, in order for lab-built soft tissues to fuse with the body’s natural soft tissues and perform the necessary physiological functions, conditions have to be just right,” explained Dr. Teo. To meet these “just right” conditions, Dr. Teo and graduate students Sara Timraz and Alia Alameri have been working to optimize the ‘bio-ink.’

Bio-ink utilizes a porous polymer material called hydrogel, which sourced from either algae or collagen, and has soft tissue-like properties and are 60%-90% water. These characteristics mimic the human body’s native soft tissues, that hold roughly 70% water, and thus provide an ideal environment for the cells to carry out their critical cross-talk and vascularization, enabling blood transport critical to maintaining organ health. However, until now, no research group had met the “just right” conditions needed to successfully fuse lab-built soft tissues made from hydrogels into the human body.

Dr. Teo’s team is working to overcome this problem through the optimization of the hydrogel by identifying parameters to further enhance its properties and make it even more biocompatible. They have published two papers on their hydrogel research, includingone in the Procedia Engineering and one in Experimental Cell Research.

“A key challenge for soft tissue engineering is that soft tissues are not just made up of one cell type – they are made from multiple cell types, and each cell requires a specific environment. For example, a vascular tissue consists of smooth muscle cells and endothelial cells. 3D printing is a great tool for this purpose because it can be leveraged to print complex tissue structures with multiple cell types. But we need to make sure that these cells are able to secrete the chemical signals between them that are required for the tissue to function effectively This is why we have to make sure the environment in the hydrogel is just right,” Dr. Teo explained.

Reprogramming Fibroblasts

To further ensure that the bioprinted soft tissue implants are functional and patient-specific, former Assistant Professor Dr. Nicolas Christoforou and graduate student Selwa Boularaoui led a research study exploring how to reprogram fibroblast cells, which are the body’s most common connective tissues cells, into a type of stem cell – known as induced pluripotent stem cells – for differentiation into various soft tissue cells. The team has already successfully demonstrated the ability to reprogram fibroblast derived pluripotent stem cells into skeletal muscle cells through a process they revealed in a paper published earlier this year in the Journal of Tissue Engineering and Regenerative Medicine. Now, the team is using the same technique to reprogram other cell types.

“Reprogramming fibroblast into other cell types is similar to the idea of differentiating embryonic stem cells, but with a lot less controversy,” Dr. Teo remarked.

In order for the tissues being implanted into a patient to be biocompatible and accepted by the patient’s body, the best option is to use the patient’s own cells. Abundant fibroblast cells from the patient can be taken and reprogrammed into the required cells, such as a smooth muscle or endothelial cells. This is an important step in the development of functional, patient-specific soft tissue replacement implants.

Conclusion

Through these projects, the University’s tissue engineering team is addressing all aspects required to grow functional, living tissues. From studying the vital communication between individual cells and learning how to develop the perfect cell environments, to developing optimized 3D bioprinters and bio-inks, the researchers are getting closer to developing tissue implants that could save hearts and lives.

Source : Masdar Institute