Making of a 3D-printed heart patch with iPSC-derived cardiomyocytes in the RMCU.

The Cardiology and the Orthopedics department of the RMCU (UMC) jointly succeeded in the making of a functional, 3D-printed cardiac patch: the original research article “Melt electrowriting allows tailored microstructural and mechanical design of scaffolds to advance functional human myocardial tissue formation” can now be found in Advanced Functional Materials. But how do different departments come together? We talked with Miguel Castilho and Alain van Mil, first shared authors from the two different research groups, to find out more about their work and how it came together in this project.

Miguel

Where do you come from?

I finished my MSc in Portugal, then moved to Germany for my PhD and arrived in Utrecht in 2015 for my post-doctoral fellowship. And was nominated Assistant Professor in Biofabrication this year.
 

What did you study?

I am a mechanical engineer with a PhD in Biomedical engineering.
What was the aim of this project?
To engineer a heart patch that would be functional and clinically relevant in size. To do this, we aimed to manufacture fibre networks with biomimetic designs and superior mechanical properties, that could be then applied in various soft tissues like heart muscle, ligaments or skin.
 

What did you bring to this project?

Being a mechanical engineer I am most interested in the fabrication process & biomaterials. I brought the knowledge of the melt writing technique, biomaterials and mechanical characterization.

Alain

Where do you come from?

I graduated from Utrecht University in 2008 and then stayed for my PhD. After my PhD I did a postdoctoral fellowship in San Diego, USA, and returned to Utrecht in 2013, where I obtained an Assistant Professor position in 2017
 

What did you study?

I did a MSc in Biomedical sciences.
 

What was the aim of this project?

To create a functional, mechanically fit, clinically relevant cardiac patch to be used for cardiac repair. And to advance our iPSC-cardiomyocyte technologies for tissue engineering purposes.
What did you bring to this project?
My role was focused on the biological aspect: iPSC-cardiomyocytes, the cells that make up the functional part of the patch. And the knowledge for translation towards the clinic.

Courtesy of Advanced Functional Materials
Courtesy of Advanced Functional Materials
 

What was the innovation in this study you just published?

The technology that we used to print the structure of the cardiac patch is called Melt –Electrowriting (MEW). It is a 3D printing technique that allows us to print with incredibly high precision fibre networks, so that we can tailor the structural and mechanical properties. This technology allowed us to print  a biomimetic fibre design that had unique flexibility and shape-recovery properties, meaning that the patch can be highly deformed without sustaining damage to its structure or cells. This mechanical behaviour enabled us to compress the patch through a catheter for example, for potential delivery in vivo with minimally invasive surgery. This is a key point for clinical relevance, as many cardiac patients often cannot undergo invasive surgery.
 

What were the main hurdles to overcome during this project?

Obtaining a functional patch that matches the adult heart was one of the main challenges: obtaining a large number of pure iPSC-cardiomyocytes with a mature phenotype is very difficult. The development of the methodology is the result of several years of research in the regenerative medicine cardiology group.
From the biofabrication point of view we also had our share of trouble: melt electro writing is a promising technology, but limited to certain materials like thermoplastics. We were the first to advance to fabricating non-linear networks, but moving away from straight fibre patterns proved to be particularly hard.
 

In your article you also described the successful delivery of the heart patch in a large in vivo animal model through minimally invasive surgery, bringing this concept closer to clinical application. What’s next?

Our final aim is to develop these cardiac patches first as support for cardiac function in patients with end-stage heart failure, and eventually to prevent progression to heart failure in myocardial infarction patients. 
For the immediate future, we want to concentrate our efforts in conducting more extensive large animal studies to assess feasibility and show functional effects, such as improved cardiac function. We also intend to make the patches more complex, by integrating other cell types in the patch.
 

What do you think will be the challenges in translating this heart patch closer to the clinic?

Ensuring integration of the patch with the native tissue may be our most difficult task to come. It will be very interesting to analyze the integration with surrounding tissue: for example, currently the patches can contract autonomously, but we don’t know if they will sync with the beating of the heart once implanted.

 To find out more about the science behind the cardiac patch, you can read the full article here.