A part of the heart muscle dies each time someone has a heart attack, and the body doesn’t fix it on its own. Adult cardiomyocytes have a very limited ability to regenerate , so the body uses scar tissue to patch the damaged area. Because scar tissue is tough, it lacks the flexibility of the original heart muscle.
But flexibility isn’t the only loss. Scar tissue on the heart doesn’t contract or carry the vital electrical signals responsible for in-sync heartbeats. This can change how the rest of theheart works and force surrounding tissue to compensate. With time, that overcompensation can lead to long-term heart failure.
Biomaterials research is trying to solve this problem by stepping in early enough to limit heart-attack damage. Since there’s no way to turn scar tissue back into healthy heart muscle, scientists have turned to protecting the cells that are still alive and giving stem cells a chance to do their job. This approach is part of ongoing research into cardiac regeneration and how damaged heart tissue might be supported after an infarction.
Why Injecting Stem Cells Is Ineffective
Stem cell therapy involves injecting stem cells with regenerative potential directly into damaged tissue so they can help rebuild what was lost. However, damaged tissue after a heart attack is not an ideal environment for these cells. . Each heartbeat creates a mechanical force that can make survival challenging for transplanted stem cells. In addition, tissue damaged by a heart attack is inflamed and has a compromised oxygen supply. Stem cell injections may improve heart function, but clinical trials show those improvements are modest. That’s because most injected stem cells don’t stay where they’re put. Instead, they may leak out, enter the bloodstream, or die in the inflammatory environment.
Biomaterials offer an alternative that addresses each of these failure points. Stem cells receive something to anchor to and are shielded enough to release therapeutic molecules at the pace the tissue can use.
Exploring Injectable Hydrogels for Cardiac Revascularization
Hydrogels behave similarly to soft biological tissue, especially in cardiac applications. These hydrogels can be injected as liquids that solidify when they reach body temperature. This solid gel fills the space where tissue was lost and helps patients avoid open-chest surgery.
Injectable hydrogels create an environment to help reduce inflammation and slow the death of surviving heart cells near the damaged site. They may also encourage new blood vessels to form and draw in progenitor cells to support repair, making them a potential tool for cardiac revascularization.
These hydrogels can be loaded with stem cells before injection, allowing the stem cells to remain at the site longer and in better conditions.
The Decellularized Cardiac Extracellular Matrix
Many promising injectable hydrogels are composed of a decellularized cardiac extracellular matrix. This matrix forms a structural scaffold that remains in place even after all cells are removed from the donor heart tissue. The material also retains natural signaling molecules to help guide heart cell behavior.
One practical advantage is that these hydrogels can be delivered through a catheter. This could allow treatments to be delivered without major surgery. Temperature-responsive formulations also help the gel remain liquid during injection and solidify only once inside the body. This type of tissue engineering approach uses biomaterials to recreate some of the structural and biological conditions needed for cardiac repair.
Cardiac Patches
Rather than being injected directly into heart tissue, cardiac patches are applied to the outside of the heart. They reinforce sections of the heart wall weakened by an infarct.
Cardiac patches applied over a weakened area can help distribute stress more evenly across the surface, slowing tissue deterioration and easing pressure on the rest of the heart. Some advanced cardiac patches can provide more than mechanical support. Researchers have recently developed 3D bioprinted cardiac patches loaded with stem cells. These tissue-engineered patches are designed to provide structural support while creating an environment that can support myocardial tissue repair.
These patches reinforce the heart wall and may support tissue regeneration. . In preclinical studies, stem cell-loaded cardiac patches helped drive the formation of new heart muscle and blood vessels in infarcted areas. Over time, these patches significantly improved the heart’s pumping function and resilience.
Conductive Scaffolds
The heart muscle contracts about 100,000 times a day in unison with electrical signals traveling through the tissue in a timed sequence. But scar tissue can interrupt that sequence by forcing electrical signals to hit a fibrotic zone that slows or reroutes the message.
However, many biomaterials are electrically insulating , with collagen, alginate, and other natural polymers that help support cells without forcing an electrical signal exchange. Conductive scaffolds do this by incorporating carbon nanotubes, graphene, conductive polymers, and other biomaterials to create a customized structure.
The scaffold provides a biomaterial that can support electrical signals between cells, similar to natural heart cells. Research has shown that growing cardiomyocytes on conductive scaffolds may improve their electrical synchronization and maturation. . And since stem cells typically behave immaturely on their own, a conductive environment can accelerate development.
Stem Cell Delivery Carriers
Many molecules needed for cardiac repair don’t remain in the body long enough to do much without support or structure. The body quickly clears anti-inflammatory agents and growth factors after an injection. So the treatment produces only a brief spike that fades before the tissue can respond.
Stem cell delivery carriers, such as nanoparticles embedded in a hydrogel or conductive scaffolding, help solve this problem. They release their cargo over time, while the molecule remains active in the damaged area long enough to produce a sustained effect. Researchers have also been developing delivery carriers that combine multiple therapeutic agents to target inflammation, cell death, and blood vessel formation simultaneously.
Requirements for Biomaterials
Biomaterials must meet three strict requirements to be deemed safe and effective for heart regeneration:
- Biocompatibility – The body must not treat the material as a threat or trigger an immune response that could worsen the environment or compromise the stem cells it was designed to protect.
- Elasticity – The material must be elastic enough to flex with heart movements without transferring abnormal stress to the surrounding muscle.
- Biodegradable – Materials should degrade as new tissue forms so that the scaffolding turns into living muscle at the right time.
Getting all three right at the same time in an unpredictable environment can make bioengineering for cardiac repair difficult. The biggest hurdle is translating lab data into clinical practice. That’s what research institutions are studying now: engineered materials and stem cells in living cardiac tissue.
Where the Research Stands
Preclinical studies and research are encouraging, with demonstrated improvements in cell survival, vascularization, functional recovery, and reduced fibrosis. Combining biomaterials and stem cells appears to outperform other approaches used independently.However, translating these findings into clinical treatments remains a slow process. .
Visit the Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI) to follow the latest advances in cardiovascular research.
