Fibrin Glue and the Cardiac Patch
A cardiac patch is a form of regenerative medicine consisting of engineered cardiomyocytes, endothelial cells and smooth muscle cells applied to the heart either in sheets or suspended in a biomaterial52. There are three stages that are employed in creating a cardiac patch: Therapy, Fabrication, and Delivery53.
Therapy
The therapy stage includes the use of stem cells in order to create the cardiomyocytes (CMs), smooth muscle cells (SMCs) and endothelial cells (ECs)14. The most common stem cells used in today’s research are human induced pluripotent stem cells (hiPSCs) due to their self replicating ability and capacity to form any cell type54. HiPSCs are human blood or skin cells that have been manipulated back into a pluripotent stem cell, similar to those seen in vitro54. More information on stem cells can be found here.
Fabrication
Once cells are created, the fabrication stage of the cardiac patch begins53. Cardiac patches can either be assembled as sheets of cells or cells suspended within a biological medium52. The first method entails cell culture on a temperature sensitive medium. Some methods use microgrooves within the medium to perfectly position the cells for maximum function55. When the temperature is higher, the medium possesses hydrophobic character, allowing adhesion of cultured cells55. The temperature of the medium is then lowered as enough cells are created, promoting a change to hydrophilic nature. This causes swelling in the cells and detachment from the medium. The mechanical forces from the swelling cause the cells to form a sheet as seen below in Figure 1. The sheet is then removed and stacked upon other sheets56. Electrical signals can travel between sheets in as little as one hour56. More details on electrical signaling and the cardiomyocyte conductive system can be found here.
The second method involves suspending the CMs, SMCs and ECs along with fibroblasts in a biomaterial such as collagen or fibrin57. This can be done via technologies such as 3D bioprinting or electrospinning57. 3D Bioprinting is a technique where cells and bioinks are used to 3D print biomaterials layer by layer. In this case, the patch design is programmed into the machine, which prints it58. Electrospinning uses electric force to create nanofibers from molecules or polymers, which can be assembled into a patch59.
Delivery
The final stage of cardiac patch application includes the delivery of the patch itself53. Patches are applied surgically and attached via fibrin glue and photocurable polymers53. Fibrin glue is especially important in securing of the patch, as it is made of biomaterials and hardens within one minute57. Fibrin glue is created by incubating the glycoprotein complex fibrogenin with serine protease thrombin, a cleaving enzyme. Thrombin cleaves fibrinogen at the carbonyl backbone of internal arginine residues, forming fibrinopeptides A and B. These molecules can then polymerize to form the fibrin polymer, displaying cohesive properties that makes it an excellent tool for cardiac patch implantation60. The mechanism of enzyme thrombin is shown in Figure 2 below cleaving a fibrinopeptide from fibrinogen, resulting in a fibrin monomer which quickly polymerizes, a restored thrombin active site, and a fibrinopeptide. This mechanism happens twice to produce fibrinopeptides A and B both shown below respectively in Figure 3 and Figure 4.
In weeks following application of the cardiac patch, native cells are observed in the synthetic tissue and cardiac function is typically improved57.
Cardiac patches are a commonly used form of regenerative medicine for cardiac repair. Making a cardiac patch includes creation of cardiomyocytes from stem cells, followed by creation and application of the patch to the body. Cardiac patches can used to treat cardiac damage that results from heart failure or an acute myocardial infarction62. More information regarding positive findings of cardiac patch implantation using neonatal rat cells can be found here.
December 8, 2023 at 4:25 pm
The fibrin patch is cool! It’s just skin graft but not from yourself and also not skin. It also interesting that the adhesive is light-cured. One consideration I would be a little worried about is that photosensitive agents, particularly adhesives, tend to leech out when not properly cured. I’m also curious if the adhesive is permanent or will breakdown over time. That being said a remarkably smart and simple (in concept, not execution) solution. A potential improvement to the page would be to box out important sections instead of just drawing a circle, as well as keeping the colors for diagrams consistent.
December 8, 2023 at 7:42 pm
I was wondering this too, after further research it appears that the patch scaffold encourages remodelling pathways with the adhered cultured cells.
December 8, 2023 at 6:23 pm
More of a minor comment: make sure capitalization on your acronyms is consistent throughout sections (you used hiPSC in “Cardiomyocyte Differentiation from Stem Cells and Fibroblasts” and HiPSC here)
December 8, 2023 at 6:30 pm
Another minor comment: Figure 2 felt a little crowded when I was going through it. I would suggest re-organizing it a little so that there is more space in-between mechanism steps; that way, it will also be clearer what label applies to what structure. I also think that, instead of putting the following statements in the figure (“His/Ser residue in Thrombin active site), you can move them to the figure caption. That way, you will clear up your figure a bit more (improves the crowding)
December 8, 2023 at 7:43 pm
Are the cultured cells that compose the cardiac patches sampled from the patient themselves individually or are companies creating general patches that require immunosuppressant medication?
December 8, 2023 at 8:56 pm
Super cool therapy and great explanation! I appreciate how you’ve broken down the sections for readability. In the fabrication section, I found myself wondering about the microgrooves and the hydrophilic techniques; I think a quick explanation of those would help with the bigger picture. Also, in the same section, you seem to have in-text citations, which are not consistent with the rest of the project.
I’d also love to see something more about the outcomes of the therapy. I appreciate linking the paper, but summarizing it quickly for the reader would be great!
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