Blood vessel regeneration is a very important process in our body, which is essential for formation and repair (or regeneration) of tissues. However, the current techniques and biomaterials lack the necessary attributes to promote angiogenesis (formation of new blood vessels) artificially, for two reasons -
1) Natural or derived biomaterials have an inherent risk of eliciting an immune response, or can cause transmission of disease causing elements;
2) Synthetic materials lack biocompatibility, i.e, the host response produced is weak, and therefore need functionalization before use. In addition to this, the traditional top-down fabrication methods do not mimic the extracellular architecture needed for regeneration to occur.
However, ongoing research by scientists at the King Abdullah University of Science and Technology (KAUST) suggests a way to combat these problems. The team had been exploring the fabrication of microgels using self-assembling peptides. These peptides are only four amino acids long, which self-assemble together in a specific fashion when in an aqueous solution to ultimately form 3D nanofibrous hydrogels resembling the extracellular matrix (ECM); these peptides are called self-assembling ultrashort peptides (SUPs). They do not elicit an immune response and can be easily made, modified and can be mass produced.
One of the peptides produced was very promising, and was made by linking together four amino acids - isoleucine, valine, phenylalanine and lysine. These peptides form a fibrous network in aqueous solution; which is put through a microfluidic device containing oil, salt and detergent. The solution becomes a gel and is broken into droplets as it passes through the device. The droplets are mechanically strong, stiff and elastic; retain their shape and size under stress; and can withstand exposure to trigger angiogenesis, the team embedded human umbilical vein endothelial cells (HUVECs) into SUP microgels, and then loading these gel droplets into a 3D SUP hydrogel containing human dermal fibroblast neonatal (HDFn) cells. These SUPs were about 300–350μm diameter in size and had a rounded structure.
To trigger angiogenesis, the team embedded human umbilical vein endothelial cells (HUVECs) into SUP microgels, and then loading these gel droplets into a 3D SUP hydrogel containing human dermal fibroblast neonatal (HDFn) cells. These SUPs were about 300–350μm diameter in size and had a rounded structure.
The team successfully grew HUVECs and HDFn cells on these SUP microgels. Features of growth, such as cell attachment, stretching, and proliferation were observed. The endothelial cells so impregnated into the microgel structure were able to migrate from the microgel to the surrounding areas. These cells then showed features such as sprouting, branching, coalescence, and lumen formation, indicative of angiogenesis.
These results demonstrated that these cell-laden microgels have great potential as a cell delivery system, to promote angiogenesis, and stimulate tissue regeneration in general. However, their use in medicine will require further research. The team has already started looking into methods to make the microgels even softer so that the cells can be delivered via the inside of the microgels, instead of only on the surface, which would make the apparent treatment even more effective. Applications of the microgels to treat ischemia in mice are underway.
Reference:
Ramirez-Calderon G, Susapto HH, Hauser CAE. Delivery of Endothelial Cell-Laden Microgel Elicits Angiogenesis in Self-Assembling Ultrashort Peptide Hydrogels In Vitro. ACS Appl Mater Interfaces. 2021 Jun 30;13(25):29281-29292. doi: 10.1021/acsami.1c03787. Epub 2021 Jun 18. PMID: 34142544. | ACS Publications
Blog by - Sohum Mohare
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