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Interview with Dr. Vahid Serpooshan, Who Created a ‘Heart Attack Patch’ With the Help of 3D Printing

According to the World Health Organization, cardiovascular disease is the number one cause of death globally. An estimated 17.9 million people died from cardiovascular disease in 2016, representing 31% of all global deaths. Treatments for all manner of cardiovascular impairments are therefore a high priority. A very prevalent ailment in that category is a heart attack which happens to over 735,000 Americans a year. 

A team of researchers led by Dr. Vahid Serpooshan, an assistant professor of Biomedical Engineering and Pediatrics at Georgia Institute of Technology and Emory University School of Medicine, have created a patch with a regenerative protein to treat the infarcted myocardium (cardiac muscle, a part of the heart that gets damaged during a heart attack). According to Georgia Institute of Technology the patch will cover the infarcted tissue with a collagen patch infused with a  protein called FSTL1, which is tailored to fit an area a little larger than the dead tissue. Dr. Serpooshan used bioprinters to develop the patch using a collagen gel. The patch is about to start its pre-clinical trial phase at Emory University’s School of Medicine in Atlanta, and a clinical trial is already ongoing in Europe for a version of this patch device. So it could be a couple more years before they are available for patient treatment. Dr. Serpooshan’s Lab (which has two locations at both Emory University and Georgia Tech) uses a multidisciplinary approach to design and develop micro/nano-scale tissue engineering technologies with the ultimate goal of generating functional tissues and organs. 3DPrint.com reached out to talk to Dr. Serpooshan about his team’s groundbreaking work. 

Professor Vahid Serpooshan sets up the medical 3D printer that will print a patch engineered to strengthen heart muscle damaged in a heart attack. (Photo by Rob Felt, Georgia Institute of Technology)

How has 3D printing helped to engineer the patch?

3D printing has been a huge help in manufacturing the patch in so many ways. It enabled us to incorporate vasculature inside the patch, something that would not have been available with traditional tissue engineering techniques, since they offer really limited potential to create complex, functional vasculature in thick, 3D tissue constructs. Additionally, it allowed us to have a controlled deposition of different cells, biomaterials, and molecules to form heterogenous, complex 3D structures that closely mimic native tissue structure. Also it provided us with patient -and disease- specificity: we utilize MR or CT imaging data obtained from patients to create 3D printed tissue constructs that precisely match the patient’s diseased or damaged tissue. Finally, bioprinting technologies have enabled tissue engineers to markedly enhance resolution and precision in various tissue manufacturing endeavors, making precision medicine even more promising.

What 3D printer do you use to create the patch?

We are mainly using two types of 3D bioprinters for this project. A BioAssemblyBot bioprinting system, made by Advanced Solutions Inc. (an American company in Louisville, Kentucky). This is the ONLY six-axis robotic arm printer in the market, with a resolution down to approximately 20 to 50 μm (microns). The second bioprinter is a BIO-X from Swedish biotech company Cellink, a pioneer in bioprinting.

An illustration of the heart with the cardiac patch already in place (Serpooshan Lab)

How long will it take to manufacture the patch?

Biomanufacturing of a cardiac patch at a clinically-relevant scale would take about 15 to 30 minutes, depending on the number of cell types involved, the vasculature design, and other factors. This enables the clinics, hopefully in the near future, to have heart attack patients come to the clinic, conduct CT or MR imaging, prepare 3D digital model of the damaged tissue, and sending it to the bioprinter to manufacture a patch device customized for that patient.

Vahid Serpooshan designing the myocardial infarct patch (Photo by Rob Felt, Georgia Institute of Technology)

Is there already a procedure in place to apply the patch?

Actually, there already is a procedure to apply the patch. We use a left thoracotomy approach to get access to the surface of the heart and suture the patch onto the epicardial layer of the heart, covering the myocardial infarction (also called a heart attack) area. There are currently some ongoing works trying to minimize the aggressiveness of this surgical procedure, potentially using catheter-based techniques.

What are the benefits of using collagen in the patch?

Collagen is the most abundant protein of the human body. This protein highly supports cell viability, proliferation, and function. It is a biodegradable protein which is a major advantage for in vivo applications, facilitating timely integration of the implant with the host tissue and avoiding long-term immunogenic complications. For our 3D bioprinting works, we use gelatin methacrylate (gelMA). Gelatin is derived from collagen (a hydrolyzed collagen) and offers similar advantages. The main advantages of gelMA for bioprinting of cardiac patches include: acceptable compatibility with cardiac cells (cardiomyocytes), tunable biomimetic mechanical properties (stiffness), controllable degradation rate, and of course, great printability (rheology properties).   

The collagen gel used to develop the 3D printed patch. (Photo by Rob Felt, Georgia Institute of Technology)

What percentage of heart disease patients will benefit from this device?

This therapy is designed for a specific group of heart attack patients, approximately one third of patients who either arrive too late to the clinics or are resistant to current catheter-based reperfusion methods and pharmacologic therapies.

If approved, Dr. Serpooshan’s patch could help over 200,000 patients per year.

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Exclusive: 3D Printed Cardiac Patch Shows Promise for Healing Damaged Hearts

Hexagonal scaffolds induce iPSC-CM contractile properties and maturation. iPSC-CM characterization before combination with scaffold, showing A) proliferating cells, B) sarcomeric structures, C) Connexin 43 (Cx43), and D) mitochondrial localization. iPSC-CMs localize to both E) hexagonal and F) rectangular fiber scaffolds, and confocal microscopy shows G,H) Cx43 expression, and increased sarcomere density, I,J) alignment, and K) length in hexagonal scaffolds compared to rectangular scaffolds. L) Beating rate at days 2, 7, 10, 11, and 14. M) Cardiac marker and maturation-related gene expression in hexagonal and rectangular scaffolds at day 7 and day 14.

After a person suffers a heart attack, they lose about half the cells in their heart, greatly weakening the organ and increasing the odds that further attacks will occur. Doctors have begun injecting cells into the heart to grow into muscle and help contractions, but 99% of those cells get washed away. But there are alternative approaches – like 3D printing. Scientists have developed 3D printed cardiac patches that can be used to repair hearts damaged by heart attacks, but only about five have been produced worldwide.

Injectability and in vivo placement of cardiac patch with hexagonal geometry. A) In vitro culture of cardiac patch consisting of iPSC-CMs in cardiac-like ECM on large hexagonal scaffolds. B) In vitro injectability, shape recovery, and C) macro image of cardiac patch after injection. D) Application and shape recovery of cardiac patch on beating porcine heart. E) Cell viability of in vitro F,G) noninjected and H,I) injected cardiac patches. J) Spontaneous beating rate of in vitro noninjected and injected cardiac patches 30 min and 2 d after injection.

In a new study entitled “Melt Electrowriting Allows Tailored Microstructural and Mechanical Design of Scaffolds to Advance Functional Human Myocardial Tissue Formation,” a group of researchers 3D printed a world-first stretchable microfiber scaffold with a hexagonal design. They then added specialized stem cells called iPS-Cardiomyocytes, which began to contract unstimulated on the scaffold. The work was then demonstrated on the actual hearts of pigs.

We spoke with the authors of the paper to learn more about the technology used by the scientists and its implications for the future.

What are the advantages of MEW relative to other technologies? 

“Melt Electrospin Writing (MEW) has distinct advantages over other 3D Printing technologies for tissue engineering applications. MEW utilises common thermoplastics used in biomedical engineering, including Polycaprolactone (PCL). The advantage of this approach is that we are able to create microfibres with diameters often in the 10 micron range, but nano-fibres also also achievable. To put this into perspective, a single strand of hair is about 50-100 microns. Printing at such resolutions allows us to mimic the native extracellular matrix (ECM) components, and allows cells to bind onto the small fibres that at similar to collagen fibrils. Additionally, MEW allows for the control over scaffold architecture, creating scaffolds with aligned fibres and controlled fibre diameters. This specific control over architecture, allows us to tailor the mechanical properties, direct cells growth and  control the movement of nutrients. Because we can modify the scaffolds properties so well, they are often used to reinforce hydrogels (as a backbone), which are typically much weaker and less tailorable.”

What is the significance of your paper?

Representation of the workflow and fabricated microfiber scaffolds. A) Schematic illustration of the in house-built MEW device used. B) Designed hexagonal microstructure. C) 3D fiber scaffold combined with iPSC-CMs and further application in vivo through minimally invasive delivery. D) Optical images of the fabricated scaffolds: detail of microstructure with hexagonal cells (with a side length of 400 µm) composed of multiple stacked aligned microfibers. Images acquired from top and lateral perspective.

“We developed patches with controlled hexagonal micro-fibre structures that had unique flexibility and shape-recovery properties, meaning that the patch can be highly deformed without sustaining damage to its structure or cells. Moreover, such novel paths allowed the maturation of contractile human iPSC-derived cardiomyocytes, which is a breakthrough in creating a functional patch that could match an adult heart. Finally, due to the patch’s flexibility, it can be compressed and pushed through a catheter for delivery in vivo with minimally invasive laparoscopic surgery.”

Why are collagen-based hydrogels so important?

“Collagen is the most abundant protein in the human myocardial tissue and for that reason an ideal biomaterial for use in myocardial tissue engineering.”

How close are we to using 3D printing in a clinical setting?

“There are already reports of 3D printed implants used in clinics, mostly metallic or ceramic based for bone repair. However, in what concerns to our heart patch’s that include biological derived components (new cell therapies, iPSC) we believe a few more years will be required. We need first to demonstrate the efficacy and safety of such approach in animal models, which we are currently planning. Also, important challenges like integration with surrounding tissue will need to be solved: 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.”

What work will you be doing next?

“We want to concentrate our efforts in conducting more extensive 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.”

Authors of the paper include Miguel Castilho, Alain van Mil, Malachy Maher, Corina H.G. Metz, Gernot Hochleitner, Jürgen Groll, Pieter A. Doevendans, Keita Ito, Joost P.G. Sluijter, and Jos Malda.

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[Images: Castilho et al, “Melt Electrowriting Allows Tailored Microstructural and Mechanical Design of Scaffolds to Advance Functional Human Myocardial Tissue Formation,” Advanced Functional Materials, 2018. Copyright Wiley – VCH Verlag GmbH & Co. KGaA. Reproduced with permission.]