Structural and Injectable Hydrogels
Hydrogels are 3D hydrophilic polymer networks capable of absorbing, swelling, and releasing biofluids, making them resemble natural living tissues and extracellular matrices. Hydrogels can be administered as a solution, then rapidly and controllably form a gel at infarcted cardiac regions63. More specifically, they can be applied through a minimally invasive procedure, typically involving a syringe or catheter. The many benefits of biomaterials, such as their inexhaustible supply, capacity for stabilization, distinctive biological activities, and compatibility with the body, have sparked significant enthusiasm for exploring their potential for mending and rejuvenating the heart (Figure 1)62.
Injectable Hydrogels
Injectable hydrogels are liquid systems in vitro, but once they arrive in the myocardium, they convert into semisolid gels under specific physiological conditions62. Some examples of hydrogels that respond to such physiological conditions are temperature-responsive hydrogels, pH-responsive hydrogels, ion-sensitive hydrogels, hypoxia-responsive hydrogels, and ROS-responsive hydrogels (reactive oxygen species). In this way, bioactive compounds and cells can be delivered in situ, promoting in situ repair and regeneration.
Despite their profound ability to prevent ventricular dilatation, enlargement or expansion of the ventricles, and enhance myocardial repair, significant limitations for injectable hydrogels persist. Injectable hydrogels have poor mechanical properties, potential immunogenicity, and the potential to be washed away rapidly from the beating heart63.
Hydrogel-Based Cardiac Patches
The limitations of injectable hydrogels can be overcome by hydrogel-based cardiac patches, which have received attention from various medical fields. Hydrogel-based cardiac patches enable drug retention with enhanced loading capability, bioavailability, biodistribution, stimulation responsiveness, controlled on-demand drug release, and multifunctional therapeutic demands63. These attributes improve efficacy and reduce systemic toxicity. Additionally, hydrogel-based cardiac patches provide mechanical support and can act as a scaffold for cells to grow and organize themselves. This added stability can facilitate the alignment and organization of cardiomyocytes, potentially improving electrical coupling and contractile function.
PEGylated Fibrin Gels
Polyethylene glycol (PEG), a biocompatible synthetic polymer, has found widespread application in tissue engineering strategies due to its remarkable attributes. It has achieved notable success owing to its water and organic solvent solubility, minimal protein adhesion, and overall non-toxic nature64.
The combination of PEG with mesenchymal stem cells, a type of adult stem cell with the potential to differentiate into various cell types, and their injection into the myocardium has demonstrated a substantial increase in cell retention and a reduction in scar tissue following myocardial infarction65. These attributes have made injectable PEG hydrogels a widely adopted approach in cardiac regeneration strategies.
Conclusion
In addressing the question of cardiac repair and regeneration, hydrogels serve as a groundbreaking solution, particularly when incorporating synthetic biopolymers. These biopolymers, like polyethylene glycol (PEG), play a crucial role in mimicking the extracellular matrix (ECM), the complex network of molecules that provides structural and biochemical support to surrounding cells. By using synthetic biopolymers within hydrogels, researchers can create a therapeutic environment that closely resembles the biological conditions of the heart. Other organically compatible compounds, such as those based on natural polymers like hyaluronic acid, collagen, or alginate, are also being investigated. These alternative materials have the potential to offer advantages in terms of biocompatibility and can provide a supportive environment for cells.
December 8, 2023 at 4:33 pm
It’s really interesting to see hydrogels being used as part of a cardiac therapy. In one of my classes, hydrogels were mainly used to deliver drugs, so seeing it deliver complete cells is an approach that I hadn’t considered. One thing that slightly concerns me is that while PEG is deemed to be quite safe, it actually doesn’t breakdown in the body very quickly. As a result, it may build up. I was curious if other more organically compatible hydrogels would also be permissible for this therapy.
December 8, 2023 at 7:30 pm
I found this section very interesting to read about! I had never previously heard about hydrogels and their applications in cardiac repair. In figure 1, I was a little confused by the right part of the picture and how the “normal heart” connects to things. Maybe some more arrows or a more detailed explanation in the caption could help with this. Also, you mention a lot of acronyms/abbreviations in this figure (like PCI, CABG) that are not included in the text. Maybe consider offering an explanation somewhere in your text or even the figure caption as to what these are.
December 8, 2023 at 7:46 pm
Can you expand further on the specific physiological conditions that encourage semisolidification of the hydrogels.
Also I was wondering if there were other applications beyond cardiology where hydrogels are used? This would be helpful for answering your first question, adding an aspect of adaptation of non-cardiac techniques to address cardiac concerns.
December 8, 2023 at 9:05 pm
Another very interesting therapy! I appreciate the concise language and how well-explained this page is. Couple of points: in the first paragraph you talk about how hydrogels are “administered as a solution”. Although you clarify how later, ‘administer’ is very broad and so defining the method/location of delivery from the outset can ensure there’s no confusion. I also agree with Kat about the abbreviations in figure 1, especially since they’re not previously defined, so this was quite confusing. Finally, I’d just add a quick point that there’s a small typo in figure 2, where you say ‘norma’ heart instead of normal.
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