Heterogeneous multi-laminar tissue constructs as a platform to evaluate aortic valve matrix-dependent pathogenicity

The present review provides a comprehensive outlook toward the possibilities of developing a functional in vitro liver tissue model on a paper platform. To this end, we first addressed the suitability of using a cellulose-based paper matrix as a substrate for cell culture applications. Then, we highlighted various patterning and substrate modification strategies that have been exploited to make the paper matrix cell-friendly. Finally, we provide an overview of the current advancements made toward developing paper-based liver tissue models and the challenges and opportunities the field has encountered.

show abstract

Section: Paper-based Liver Model: Addressing Current Challenges and A...mentioning

confidence: 99%

Paper-Based Cell Culture: Paving the Pathway for Liver Tissue Model Development on a Cellulose Paper Chip

Agarwal

Borrelli

Makvandi

et al. 2020

ACS Appl. Bio Mater.

View full text Add to dashboard Cite

show abstract

“…Aikawa and colleagues developed a 3D system using a hydrogel made from photo-crosslinked HA and gelatin and found that VICs encapsulated into the 3D hydrogels only activate into myofibroblasts when exposed to exogenous environmental cues, and they did not observe apoptotic-driven calcification [ 13 ]. Grande-Allen and colleagues used a layered filter paper-based cell culture system to determine the relative amount of fibrillar collagen within a 3D construct that regulates the osteogenic capacity of VICs [ 14 ]. As the osteogenic medium is utilized in these 3D models, they provide little insight into the dystrophic pathway.…”

Section: Introductionmentioning

confidence: 99%

The Role of Apoptosis and Oxidative Stress in a Cell Spheroid Model of Calcific Aortic Valve Disease

Coutts,

Baldwin,

Jebeli

et al. 2023

Cells

View full text Add to dashboard Cite

Calcific aortic valve disease (CAVD) is the most common heart valve disease among aging populations. There are two reported pathways of CAVD: osteogenic and dystrophic, the latter being more prevalent. Current two-dimensional (2D) in vitro CAVD models have shed light on the disease but lack three-dimensional (3D) cell–ECM interactions, and current 3D models require osteogenic media to induce calcification. The goal of this work is to develop a 3D dystrophic calcification model. We hypothesize that, as with 2D cell-based CAVD models, programmed cell death (apoptosis) is integral to calcification. We model the cell aggregation observed in CAVD by creating porcine valvular interstitial cell spheroids in agarose microwells. Upon culture in complete growth media (DMEM with serum), calcium nodules form in the spheroids within a few days. Inhibiting apoptosis with Z-VAD significantly reduced calcification, indicating that the calcification observed in this model is dystrophic rather than osteogenic. To determine the relative roles of oxidative stress and extracellular matrix (ECM) production in the induction of apoptosis and subsequent calcification, the media was supplemented with antioxidants with differing effects on ECM formation (ascorbic acid (AA), Trolox, or Methionine). All three antioxidants significantly reduced calcification as measured by Von Kossa staining, with the percentages of calcification per area of AA, Trolox, Methionine, and the non-antioxidant-treated control on day 7 equaling 0.17%, 2.5%, 6.0%, and 7.7%, respectively. As ZVAD and AA almost entirely inhibit calcification, apoptosis does not appear to be caused by a lack of diffusion of oxygen and metabolites within the small spheroids. Further, the observation that AA treatment reduces calcification significantly more than the other antioxidants indicates that the ECM stimulatory effect of AA plays a role inhibiting apoptosis and calcification in the spheroids. We conclude that, in this 3D in vitro model, both oxidative stress and ECM production play crucial roles in dystrophic calcification and may be viable therapeutic targets for preventing CAVD.

show abstract

“…Both TGF-β1 and BMP-2 are believed to play a role in VIC nodule formation [25][26][27][28] . However, these signaling pathways are complex [29] and are further convoluted by mechanical stimuli [30] . In order to further elucidate the role of these proteins on VIC activation, there is an increased desire for in vitro models that allow for the controlled presentation of matrix signals in a biologically relevant context [31] .…”

Section: Introductionmentioning

confidence: 99%

Bioorthogonal click chemistries enable simultaneous spatial patterning of multiple proteins to probe synergistic protein effects on fibroblast function

Caldwell

Azagarsamy

et al. 2020

Biomaterials

View full text Add to dashboard Cite

Heterogeneous multi-laminar tissue constructs as a platform to evaluate aortic valve matrix-dependent pathogenicity

Cited by 6 publications

References 37 publications

Paper-Based Cell Culture: Paving the Pathway for Liver Tissue Model Development on a Cellulose Paper Chip

Paper-Based Cell Culture: Paving the Pathway for Liver Tissue Model Development on a Cellulose Paper Chip

The Role of Apoptosis and Oxidative Stress in a Cell Spheroid Model of Calcific Aortic Valve Disease

Bioorthogonal click chemistries enable simultaneous spatial patterning of multiple proteins to probe synergistic protein effects on fibroblast function

Contact Info

Product

Resources

About