Key result
A 3D-bioprinted hydrogel model highly recapitulated the human calcific aortic valve disease cellular proteome compared to traditional 2D monoculture (94% vs. 70% of proteins).
Why the study?
No pharmacotherapeutics are available to treat CAVD due to lacking models that recapitulate its complex environment and lack of benchmarking novel engineered AV-model performance.
A 3D-bioprinted hydrogel model of calcific aortic valve disease significantly outperforms traditional 2D cultures in recapitulating the human CAVD cellular and extracellular vesicle proteome, offering a promising high-throughput platform for drug discovery.
3D-bioprinted CAVD models improve proteomic fidelity over 2D; leaves open translation to human drug screening platforms.
In calcific aortic valve disease (CAVD), mechanosensitive valvular cells respond to fibrosis- and calcification-induced tissue stiffening, further driving pathophysiology. No pharmacotherapeutics are available to treat CAVD, due to the lack of: 1) appropriate experimental models that recapitulate this complex environment; and 2) benchmarking novel engineered AV-model performance. We established a biomaterial-based CAVD model mimicking the biomechanics of the human AV disease-prone fibrosa layer, 3D-bioprinted into 96-well arrays. LC-MS/MS analyses probed the cellular proteome and vesiculome to compare the 3D-bioprinted model vs. traditional 2D monoculture, against human CAVD tissue. The 3D-bioprinted model highly recapitulated the CAVD cellular proteome (94% vs. 70% of 2D proteins). Integration of cellular/vesicular datasets identified known and novel proteins ubiquitous to AV calcification. This study explores how 2D vs. 3D-bioengineered systems recapitulate unique aspects of human disease, positions multi-omics as a novel technique for the evaluation of high throughput-based bioengineered model systems and potentiates future drug discovery.
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Clift et al. (2023) studied Calcific aortic valve disease (CAVD) (n=10). 3D-bioprinted hydrogel model vs. 2D monoculture was evaluated on Recapitulation of CAVD cellular proteome. A 3D-bioprinted hydrogel model highly recapitulated the human calcific aortic valve disease cellular proteome compared to traditional 2D monoculture (94% vs. 70% of proteins).
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