March 15, 2022 by admin 0 Comments

Dr. INVIVO 4D2 User Story : Dr. Carmine Gentile

“Nowadays, 3D bioprinting systems are more user-friendly than in the past and fairly intuitive, allowing less experts to successfully work with cells, hydrogels and 3D bioprinters”

I am Dr Carmine Gentile, I am a Senior Lecturer (Assistant Professor), Group Leader of Cardiovascular Regeneration and Director of the Advanced Biofabrication Facility at the University of Technology Sydney. I lead a multidisciplinary team focusing on the biofabrication of living and functional heart tissues for in vitro and in vivo applications by combining stem cells and 3D bioprinting technology.

3D Bioprinter, a Potential Problem Solver

Every ten minutes one Australian suffers from a heart attack. On average, the damage will progressively develop as cardiac fibrosis (stiffening of the heart) and heart failure. Current gold-standard treatment for heart failure patients is a heart transplant. However, it is not suitable for everyone due to limitations in donor-receiver match. At the same time, even if a patient can receive a heart transplant, there is a high mortality rate within few years.

Our research aims at providing evidence that cells from the same patient can be used to create viable and functional heart patches to repair the damaged heart tissue in a patient. Currently we are testing how to do this by using patient-derived stem cells together with 3D bioprinting technology, by creating layer-by-layer a personalized treatment to improve how a failing heart can gain function and provide a better quality of life for patients and their families.

Dr. Carmine and his Ph.D student Niina Matthews

The “mini-hearts” I have developed are built on the natural aggregation of cardiac cells, which have been either isolated by heart biopsies or with patient-derived stem cells. In the human heart, blood vessels are critical for the proper development of the muscle wall, and by replicating this proper in the test tube we have successfully prevented the cell death in the center of the bioengineered heart. We use mini-hearts as building blocks, similar to a Lego approach, where the deposition of multiple mini-hearts through the 3D bioprinter in a 3D structure allows the generation of complex vascularized heart tissue that better mimic the native human heart. We were able to compare this process with one similar that is used by our body by creating smaller parts that are assembled to create bigger ones. Single cells are not able to directly form complex 3D tissues in one step, and we wanted to replicate this process by bringing together small pieces of heart tissues that can assemble together thanks to a 3D bioprinter.

My Experience with Dr. INVIVO 4D2

The unique features of the INVIVO bioprinter consist of the ability to fully control the temperature of the chamber, allowing precise control over the nozzle (a critical requirement especially in case of temperature sensitive hydrogels). The ability to work simultaneously with two printheads that may integrate either two hydrogels or a hydrogel with a plastic filament has allowed us to explore new venues for our research.

In particular, we are currently testing how to create personalized 3D bioprinted heart patches that better suit the needs of the surgeons and the patients. We will be sharing our latest results once they will be available to be published, as we are currently working on the early phases of the project with the help of clinicians.

10㎟ AlgGel patches 3D bioprinted using Dr. INVIVO 4D2 (“Printability, Durability, Contractility and Vascular Network Formation in 3D Bioprinted Cardiac Endothelial Cells Using Alginate–Gelatin Hydrogels,” Roche et al., 2021, https://doi.org/10.3389/fbioe.2021.636257)

Recommending You To Be a 3D Bio Printer Pioneer

I always start by explaining students that they, as bioengineers, become the “masterchefs” of science in their research. They need to look for the right ingredients (cells and hydrogels) and use specific tools (including the 3D bioprinter) to generate a tissue, in a similar fashion to what a chef does while cooking or baking. Finding the right “recipe” based on numerous tests is critical before a tissue can be used in a patient, which requires also understanding on how to better replicate the native tissue with the ingredients and tools we have access to. Once the recipe has been defined, the combination of cells and hydrogels create the “biological ink” or “bio-ink”, which is then used by the 3D bioprinter to create the tissue using a layer-by-layer approach. The generation of a 3D bioprinted tissue aims at providing a three-dimensional, complex environment for cells to live in, similar to the type of complex scenario they are exposed to in our body. Cells have been used in the past as monolayer culture, and we know the limitations of this approach, especially in translating from the bench to the bedside. 3D bioprinting of tissues using optimal conditions for cells to live during and after the printing process is critical for the success of this approach and a better understanding of the technology would be preferred for someone starting to work in this field. However, nowadays 3D bioprinting systems have been developed that are user-friendly and fairly intuitive, allowing “less experts” to successfully work with cells, hydrogels and 3D bioprinters.

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