Exploring nano-scale scaffolds for mending damaged hearts



EU-funded researchers have used advanced nanomaterials to engineer heart tissue, and have explored the development of innovative stem cell-based therapies that could greatly improve the recovery rates of people who have suffered heart attacks. The researchers have made some preliminary tests on rats, the basis for further study. An automated microscope and software developed in the project are currently being commercialised.

Across Europe, thousands of people suffer heart attacks every day. The majority survive but many experience ongoing symptoms for years or even the rest of their lives, and many suffer subsequent attacks. Their chances of making a full recovery could be greatly improved by emerging cell therapy and tissue engineering techniques for repairing damaged heart muscle that was investigated by European and Israeli researchers in the EU-funded NANOCARD project.

“After a heart attack, the damaged heart tissue will stiffen and myocardial scarring will occur. But this tissue cannot contract, thereby reducing the heart’s ability to pump blood and the patients’ ability to make a full recovery,” says project coordinator Joachim Spatz of the Max Planck Institute for Intelligent Systems in Stuttgart, Germany. “Our goal was to stimulate the regeneration of heart muscle with active cardiac tissue.”

Spatz coordinated the team of researchers from universities, research institutes and private companies in advancing techniques for heart muscle repair through the use of stem and progenitor cells – cells that have yet to differentiate into specific cell types.

For repairing damaged heart tissue, an increase in functional heart cells, called cardiomyocytes, are needed. The difficulty is ensuring that stem and progenitor cells stay in place and start to generate cardiomyocytes after they are implanted.

Rather than directly injecting the stem and progenitor cells near the damaged tissue – a trial and error approach that has produced inconsistent results – the NANOCARD team designed a microscopic implant by stacking nanometre-scale sheets of biodegradable polymers to create a 3D structure, or scaffold. The scaffold, which features a specifically-tailored micro-porous surface, enables the selective adhesion of stem and progenitor cells and helps direct their differentiation.

Synthetic matrix to stimulate cell differentiation
“Stem cells differentiate based on a matrix of parameters in their physical and chemical environment. We sought to replace the natural matrix with a synthetic matrix to control these parameters in a very systematic and precise way,” Spatz explains.

To determine the precise parameters needed on the scaffold to stimulate cardiac cell generation, the project team developed advanced biochips onto which cardiac progenitor cells could be placed.

An automated microscope and software, developed by Israeli project partner Idea Bio Medical, was then used to analyse the response of the cells to different environmental parameters and determine the optimum matrix to stimulate cardiomyocyte generation. Idea Bio Medical is currently commercialising the tools, which also have applications in other areas of stem cell research.

“The idea is that this nanometre-scale scaffold can then be implanted near the damaged heart tissue to stimulate the regeneration of functional cardiac cells in a much more precise and localised manner,” Spatz says.

The NANOCARD team tested their approach during in vivo trials on the hearts of rats. No indication of cardiac or systemic toxicity of the implanted scaffolds was found, but neither did the researchers demonstrate any positive effect on cardiac function – a factor Spatz puts down to the limited duration and scale of the trial.

However, in vitro tests successfully showed that the technique is effective at directing the differentiation of cardiac progenitor cells into cardiac tissue – a key achievement that will serve as the basis for further study.
With that goal in mind, several of the NANOCARD partners are continuing to work together and are seeking funding to follow up research that is likely to include more extensive in vivo trials.

This innovation was made possible by Israel’s continued participation in the official Horizon 2020 fund, managed in Israel by ISERD part of The Israel Innovation Authority (Formerly the Office of the Chief Scientist and MATIMOP). The initiative has taken Israeli R&D to the next level with the help of ground-breaking collaboration between scientists in Israel and Europe, as well as essential funding and support.

Project details
Project acronym: NANOCARD
Participants: Germany (Coordinator), Switzerland, Sweden, Italy, Israel, France, Austria
Proj. N° 229294
Total costs: € 5 263 512,4
EU contribution: € 3 806 600
Duration: January 2010 – December 2013