Kidney tubulointerstitium: a microfluidic bioprinting approach

by Gabriele Addario, MERLN Institute

It is estimated that 10% of the worldwide population suffers from chronic kidney disease (CKD) with a rising tendency. Patients with CKD have limited treatment options and novel therapies that could halt or even reverse the progression of CKD are urgently needed. Bioprinting is considered one of the most promising approaches to generate novel 3D in vitro models and organ-like constructs to investigate underlying pathomechanisms of kidney diseases.

This study aimed at establishing a method to isolate primary renal cells in an easy and reproducible way. These cells were used in a new bioprinting platform laying the foundation for the development of a 3D renal tubulointerstitium model for in vitro studies. Primary murine tubular (pmTECs), endothelial and fibroblast cells were successfully isolated, but further optimization is required for the culture and expansion of primary endothelial cells.

Therefore, an endothelial cell line (HUVECs) and pmTECs were combined with polysaccharide biomaterial ink solutions and processed with a microfluidic 3D bioprinter, leading to high cell viability and metabolic activity. Core-shell bioprinted constructs with HUVECs and pmTECs were manufactured mimicking tubules.

In conclusion, microfluidic bioprinting strategy could be used to build a novel 3D kidney in vitro model.



What drives you?

As a biomedical engineer I like to constantly challenge me to develop novel solutions to a problem. Within the field of biofabrication, summing up the new developments and the exponential scientific progress to build tissue and organ-like units in the lab we are still far from creating an impact in clinics and in the patient. To contribute, I`m creating functional in vitro models to study renal disease and to create relevant platforms to develop in the future novel therapies for patients with chronic kidney disease. Together, we can really make a difference on the long term, leading to better solutions for the healthcare.

Why should the delegate attend your presentation?

In the field of biofabrication, the term bioprinting is more often misused. Many studies report bioprinting approaches, but in most cases cells are not included in the process and the outcome of these studies fails short on the true potential of these approaches.
With my presentation, I would like to give a brief overview about our first work on microfluidic bioprinting at MERLN. Our goal is to create an in vitro model of the kidney tubulointerstitium, which will be used to investigate renal fibrosis progression in the future. The reduced dimensions of our model and the cell types used make our model of great interest for the screening or future development of therapies.

What emerging technologies/trends do you see as having the greatest potential in the short and long run?

Bioprinting has quickly moved forward in the last years. In the past, researchers were interested in proving the viability of bioprinted cells throughout the processes, while now complex in vitro bioprinted models have been proposed. These models may allow a better understanding of certain diseases, tackling pathomechanisms from a different prospective, compared to the traditional approaches. Microfluidic bioprinting may have a relevant role in this, as the increasing number of publications is suggesting.

What kind of impact do you expect them to have?

Microfluidic bioprinting allows to produce better results in terms of resolution (filaments from 50 µm in diameter) and cell viability, reducing the shear stresses, if compared to the classical types of extrusion-based bioprinters. Furthermore, this technology allows the inclusion of multiple cell populations which will gradually allow to mimicking more closely the complex architecture of human tissues or organs.

What are the barriers that might stand in the way?

There are many challenges within the field of biofabrication, and in particular bioprinting. Examples of the bioprinting challenges are the need of suitable biomaterial inks and cells, the formulation of bioinks, the maturation post-printing and the level of functionality of the bioprinted constructs.

In the last years, the field has produced encouraging results, which will ultimately allow us to study more closely what happens in vivo, allowing us to better understanding disease progression in vitro.

“Special Quote”

First steps towards kidney fibrosis model, a long journey towards novel therapies

Gabriele Addario received his Bachelor’s degree and Master’s degree in Biomedical Engineering, with a specialization in biomechanics and biomaterials at Politecnico of Milano, Italy. Pursuing his passion for biofabrication and in particular bioprinting, in June 2019 he started his Master Internship in the Complex Tissue Regeneration (CTR) department of MERLN on kidney bioprinting.

In February 2020, Gabriele started working as a PhD candidate in CTR. The main goal of his project is the implementation of bioprinting techniques to produce an in vitro model, allowing the investigation of kidney fibrosis. Kidney fibrosis is considered the best predictor of the development of all chronic kidney diseases, considering 10% of the worldwide population suffers from impaired renal functions.

The MERLN Institute for Technology-Inspired Regenerative Medicine strives to maintain a leading position in the field of biomedical engineering by combining creative research with training a generation of interdisciplinary scientists. MERLN’s activities operate at the interface of biology, engineering and medicine to maximise impact at the level of public involvement and the commercialisation of research. MERLN’s vision is based on sharing knowledge, infrastructure, and ambition!

3D Bioprinting Conference focuses on 3D bioprinting, the most disruptive application of 3D printing in the medical world, and latest developments and applications in the field. The conference is addressed to health care innovators, from tissue engineers to biomedical researchers and from hardware manufacturers to bio medical material suppliers. It is not a purely academic conference, but an innovative event bringing together brilliant minds and discoveries. It is part of 3D Medical Series, which includes other conferences dedicated to 3D medtech printing, 3D dental printing and 3D pharmaceutical printing.

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