Some of the Details Involved in Creating Heart Tissue That Beats

In recent years a number of research groups have made progress towards building heart tissue that is capable of beating. This is obviously quite necessary if the end goal is a completely functional heart, produced from a patient's stem cells alone, but even if considering the production of small tissue patches for an injured heart researchers must be able to produce muscle fibers that behave in the right way, otherwise it is just as likely that a treatment would prove to be harmful rather than helpful.

Decellularization is still well ahead of other approaches in terms of the ability to produce large amounts of tissue for transplant or testing, as well as in the production of tissue that accurately reproduces the complex structure of an organ. Creating the blood vessel network needed to support larger tissue sections is perhaps the greatest present challenge facing tissue engineers, though once past that a whole range of other issues related to organ structure will be next in line. The structural challenges are precisely why decellularization is out in front in terms of technical outcomes: a donor organ scaffold with all its cells stripped neatly provides the guiding structure and chemical cues needed to reconstruct the blood vessels and other details required for full function. At some point it will be necessary to break free from the need for donor organs, however. Decellularization is only a stepping stone between today and a world in which organs can be printed to order from a simple skin sample.

Here is news of recent work on the details of heart tissue engineering, with a focus on improving the electrical aspect associated with the beating of a living heart. The fine details of muscle structure are absolutely vital here, and hard to get right. There is a still a great deal of experimentation between here and a functional heart grown from cells or bioprinted, and there is a need for flexible, reliable technology platforms to enable that experimentation:

Building heart tissue that beats

When a heart gets damaged, such as during a major heart attack, there's no easy fix. But scientists working on a way to repair the vital organ have now engineered tissue that closely mimics natural heart muscle that beats, not only in a lab dish but also when implanted into animals. To tackle the challenge of engineering heart muscle, Khademhosseini and Annabi have been working with natural proteins that form gelatin-like materials called hydrogels. "The reason we like these materials is because in many ways they mimic aspects of our own body's matrix," Khademhosseini said. They're soft and contain a lot of water, like many human tissues.

His group has found that they can tune these hydrogels to have the chemical, biological, mechanical and electrical properties they want for the regeneration of various tissues in the body. But there was one way in which the materials didn't resemble human tissue. Like gelatin, early versions of the hydrogels would fall apart, whereas human hearts are elastic. The elasticity of the heart tissue plays a key role for the proper function of heart muscles such as contractile activity during beating. So, the researchers developed a new family of gels using a stretchy human protein aptly called tropoelastin. That did the trick, giving the materials much needed resilience and strength.

But building tissue is not just about developing the right materials. Making the right hydrogels is only the first step. They serve as the tissue scaffold. On it, the researchers grow actual heart cells. To make sure the cells form the right structure, Khademhosseini's lab uses 3-D printing and microengineering techniques to create patterns in the gels. These patterns coax the cells to grow the way the researchers want them to. The result: small patches of heart muscle cells neatly lined up that beat in synchrony within the grooves formed on these elastic substrates. These micropatterned elastic hydrogels can one day be used as cardiac patches. Khademhosseini's group is now moving into tests with large animals. They are also using these elastic natural hydrogels for the regeneration of other tissues such as blood vessels, skeletal muscle, heart valves and vascularized skin.

Hybrid hydrogels containing vertically aligned carbon nanotubes with anisotropic electrical conductivity for muscle myofiber fabrication

Biological scaffolds with tunable electrical and mechanical properties are of great interest in many different fields, such as regenerative medicine, biorobotics, and biosensing. In this study, dielectrophoresis (DEP) was used to vertically align carbon nanotubes (CNTs) within methacrylated gelatin (GelMA) hydrogels in a robust, simple, and rapid manner.

Skeletal muscle cells grown on vertically aligned CNTs in GelMA hydrogels yielded a higher number of functional myofibers than cells that were cultured on hydrogels with randomly distributed CNTs and horizontally aligned CNTs, as confirmed by the expression of myogenic genes and proteins. In addition, the myogenic gene and protein expression increased more profoundly after applying electrical stimulation along the direction of the aligned CNTs. We believe that platform could attract great attention in other biomedical applications, such as biosensing, bioelectronics, and creating functional biomedical devices.

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