Speaker
Description
Diabetes mellitus (DM) is a complex metabolic disease characterized by impaired glucose metabolism (hyperglycemia), leading to severe and long-term complications, such as kidney failure, stroke, peripheral neuropathy, nephropathy and, above all, foot ulcers.
In the last years, 2D in-vitro cell culture systems and 3D in-vivo animal models have been particularly useful in understanding the pathophysiology of diabetic skin. However, these cannot fully represent the disease because of (i) the oversimplification of human physiology and the lack of typical cell-to-cell interactions occurring in an in vivo microenvironment (2D cell culture systems), and (ii) critical differences between species, including metabolic processes, enzymes, and membrane proteins (3D animal models). Trying to overcome these limitations, the use of cell-laden hydrogels, consisting of either extracellular matrix-derived materials or biocompatible natural polymers that provide a microenvironment similar to that of natural tissues, has emerged as a promising alternative for the biofabrication of 3D in vitro models.
In this framework, the research work in the network of D34H project (Digital Driven Diagnostics, pronostics and therapeutics for Sustainable Health care) focuses on the light-assisted bioprinting of a novel 3D in vitro model of diabetic skin useful for drug and therapy screening, using Type-B bovine gelatin methacryloyl (GelMA) derivatives as hydrogel precursors.
In particular, two different strategies are being followed. The first approach involves the biofabrication of cell-laden GelMA-based hydrogels and their subsequent immersion in high glucose culture media in order to evaluate both the cellular behavior and wound-healing mechanisms in hyperglycemic environments resembling those typically associated with DM.
The second strategy aims to further modify the structure of the hydrogel precursor trying to reproduce at the synthesis stage, those structural changes normally affecting the native extracellular-matrix as a result of non-enzymatic glycation of proteins, lipids, and nucleic acids, occurring in diabetic hyperglycemic environments. Accordingly, GelMA is glycosilated with ribose by following the path of Maillard reactions. The so-obtained glycated biopolymer (GLY-GelMA) will be used as innovative biopolymer for the bioprinting of cell-laden hydrogels to be tested in hyperglycemic environments, following the same procedure as described above.
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