An Injected Tissue Engineered Heart Patch

Tissue engineers are still limited in the size of tissues they can produce, as there remains no reliable solution for the generation of capillary networks. The thickness of tissue that can be constructed is thus limited to the distance that nutrients can perfuse in the absence of capillaries. The production of thin sheets is viable under these constraints, and a number of research groups are investigating methods of spurring heart regeneration by applying a sheet - a patch - of suitable cells onto the exterior of this organ. The research noted here is an example of the type, merging this line of work with efforts to produce tissue scaffolds that can be injected, rather than requiring surgery to implant.

Repairing heart tissue destroyed by a heart attack or medical condition with regenerative cells or tissues usually requires invasive open-heart surgery. But now researchers have developed a technique that lets them use a small needle to inject a repair patch a little smaller than a postage stamp, without the need to open up the chest cavity. The team are experts in using polymer scaffolds to grow realistic 3D slices of human tissue in the lab. One of their creations, AngioChip, is a tiny patch of heart tissue with its own blood vessels - the heart cells even beat with a regular rhythm.

Such lab-grown tissues are already being used to test potential drug candidates for side effects, but the long-term goal is to implant them back into the body to repair damage. "If an implant requires open-heart surgery, it's not going to be widely available to patients. It's just too dangerous." After a heart attack the heart's function is reduced so much that invasive procedures like open-heart surgery usually pose more risks than potential benefits.

The researchers spent nearly three years developing a patch that could be injected, rather than implanted. After dozens of attempts, they found a design that matched the mechanical properties of the target tissue, and had the required shape-memory behaviour: as it emerges from the needle, the patch unfolds itself into a bandage-like shape. The shape-memory effect is based on physical properties, not chemical ones. This means that the unfolding process doesn't require additional injections, and won't be affected by the local conditions within the body. Over time, the scaffold will naturally break down, leaving behind the new tissue.

The next step was to seed the patch with real heart cells. After letting them grow for a few days, the team injected the patch into rats and pigs. Not only does the injected patch unfold to nearly the same size as a patch implanted by more invasive methods, the heart cells survive the procedure well. "When we saw that the lab-grown cardiac tissue was functional and not affected by the injection process, that was very exciting. Heart cells are extremely sensitive, so if we can do it with them, we can likely do it with other tissues as well." The team also showed that injecting the patch into rat hearts can improve cardiac function after a heart attack: damaged ventricles pumped more blood than they did without the patch.


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