Hyaluronic acid regulates heart valve interstitial cell contraction in fibrin-based scaffolds

Lei, Ying; Bortolin, Luciano; Benesch-Lee, Frank; Oguntolu, Teniola; Dong, Zhijie; Bondah, Narda; Billiar, Kristen L.

doi:10.1016/j.actbio.2021.09.046

Cited by 12 publications

(18 citation statements)

References 54 publications

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“…These results confirmed that HA did not exacerbate late-stage mineralization, but did induce significant alterations in cellular behavior (increased proliferation, α-SMA expression, and invasion rates), when compared to collagen-only controls. Lei et al found that the incorporation of HA into tissue engineered scaffolds seeded with porcine cells promoted cell-mediated tissue remodeling, increased matrix density and stiffness, and regulated tissue contraction ( 47 ). Similarly, the current study provides evidence that HA may play a role in matrix regeneration and could be a potential tool for directing tissue activity toward non-pathological matrix remodeling.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, the current study provides evidence that HA may play a role in matrix regeneration and could be a potential tool for directing tissue activity toward non-pathological matrix remodeling. Recapitulating the role of HA in valvulogenesis could yield greater insight into improved methods for scaffolding and selection of biomaterials for novel tissue engineered valves ( 47 , 48 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recapitulating the role of HA in valvulogenesis could yield greater insight into improved methods for scaffolding and selection of biomaterials for novel tissue engineered valves (47,48).…”

Section: Discussionmentioning

confidence: 99%

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Glycosaminoglycans affect endothelial to mesenchymal transformation, proliferation, and calcification in a 3D model of aortic valve disease

Bramsen

Alber

Mendoza

et al. 2022

Front. Cardiovasc. Med.

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Calcific nodules form in the fibrosa layer of the aortic valve in calcific aortic valve disease (CAVD). Glycosaminoglycans (GAGs), which are normally found in the valve spongiosa, are located local to calcific nodules. Previous work suggests that GAGs induce endothelial to mesenchymal transformation (EndMT), a phenomenon described by endothelial cells’ loss of the endothelial markers, gaining of migratory properties, and expression of mesenchymal markers such as alpha smooth muscle actin (α-SMA). EndMT is known to play roles in valvulogenesis and may provide a source of activated fibroblast with a potential role in CAVD progression. In this study, a 3D collagen hydrogel co-culture model of the aortic valve fibrosa was created to study the role of EndMT-derived activated valvular interstitial cell behavior in CAVD progression. Porcine aortic valve interstitial cells (PAVIC) and porcine aortic valve endothelial cells (PAVEC) were cultured within collagen I hydrogels containing the GAGs chondroitin sulfate (CS) or hyaluronic acid (HA). The model was used to study alkaline phosphatase (ALP) enzyme activity, cellular proliferation and matrix invasion, protein expression, and calcific nodule formation of the resident cell populations. CS and HA were found to alter ALP activity and increase cell proliferation. CS increased the formation of calcified nodules without the addition of osteogenic culture medium. This model has applications in the improvement of bioprosthetic valves by making replacements more micro-compositionally dynamic, as well as providing a platform for testing new pharmaceutical treatments of CAVD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Glycosaminoglycans affect endothelial to mesenchymal transformation, proliferation, and calcification in a 3D model of aortic valve disease

Bramsen

Alber

Mendoza

et al. 2022

Front. Cardiovasc. Med.

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“…Leaflet substrates with high mechanical properties have shown excessive myofibroblast gene expression that causes fibrosis and leaflet retraction. 13,19 Thus, the native-like mechanical properties of the PCL/PLCL constructs might have prevented excessive myofibroblast gene expression that may cause fibrosis and leaflet retraction. 74 The COLA1 expression in the PCL/PLCL constructs was more significant than in the PCL constructs (Figure 8c).…”

Section: Histologymentioning

confidence: 99%

“…These non-native characteristics of the substrates have led to prolonged VIC activation, which caused leaflet retraction and calcification in the tissue-engineered heart valves. VICs cultured on trilayer substrates with anisotropic structural and mechanical properties exhibit lower VIC activation and lower rates of calcification and retraction. − Further, our previous work has shown that trilayered cell-cultured constructs developed in vitro from a trilayer substrate show resistance to leaflet retraction. , Also, trilayered tissue constructs produced from trilayer leaflet substrates in the subcutaneous space of the rat model had a distinct native-like structure and protein quantities similar to that in a native leaflet. , Thus, developing substrates with both anisotropic structural and mechanical properties could be essential for successful heart valve tissue engineering …”

Section: Introductionmentioning

confidence: 99%

Elastomeric Trilayer Substrates with Native-like Mechanical Properties for Heart Valve Leaflet Tissue Engineering

Snyder

Jana

2023

ACS Biomater. Sci. Eng.

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Heart valve leaflets have a complex trilayered structure with layer-specific orientations, anisotropic tensile properties, and elastomeric characteristics that are difficult to mimic collectively. Previously, trilayer leaflet substrates intended for heart valve tissue engineering were developed with nonelastomeric biomaterials that cannot deliver native-like mechanical properties. In this study, by electrospinning polycaprolactone (PCL) polymer and poly(l-lactide-co-ε-caprolactone) (PLCL) copolymer, we created elastomeric trilayer PCL/PLCL leaflet substrates with native-like tensile, flexural, and anisotropic properties and compared them with trilayer PCL leaflet substrates (as control) to find their effectiveness in heart valve leaflet tissue engineering. These substrates were seeded with porcine valvular interstitial cells (PVICs) and cultured for 1 month in static conditions to produce cell-cultured constructs. The PCL/PLCL substrates had lower crystallinity and hydrophobicity but higher anisotropy and flexibility than PCL leaflet substrates. These attributes contributed to more significant cell proliferation, infiltration, extracellular matrix production, and superior gene expression in the PCL/PLCL cell-cultured constructs than in the PCL cell-cultured constructs. Further, the PCL/PLCL constructs showed better resistance to calcification than PCL constructs. Trilayer PCL/PLCL leaflet substrates with native-like mechanical and flexural properties could significantly improve heart valve tissue engineering.

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Emerging technologies for cardiac tissue engineering and artificial hearts

Sun

Wang

et al. 2023

Smart Medicine

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Heart diseases, especially cardiovascular diseases, have brought heavy burden on society for their high morbidity and mortality. In clinical, heart transplantation is recognized as an effective strategy to rescue the lives of patients, while it may suffer from lack of donors and possible immune responses. In view of this, tremendous efforts have been devoted to developing alternative strategies to recover the function and promote the regeneration of cardiac tissues. As an emerging field blending cell biology and material science, tissue engineering technique allows the construction of biomimetic living complexes as organ substitutes for heart repair. In this review, we will present the recent progress in cardiac tissue engineering and artificial hearts. After introducing the critical elements in cardiac tissue engineering, we will present advanced fabrication methods to achieve scaffolds with desired micro/nanostructure design as well as the applications of these bioinspired scaffolds. We will also discuss the current dilemma and possible development direction from a biomedical perspective.

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Hyaluronic acid regulates heart valve interstitial cell contraction in fibrin-based scaffolds

Cited by 12 publications

References 54 publications

Glycosaminoglycans affect endothelial to mesenchymal transformation, proliferation, and calcification in a 3D model of aortic valve disease

Glycosaminoglycans affect endothelial to mesenchymal transformation, proliferation, and calcification in a 3D model of aortic valve disease

Elastomeric Trilayer Substrates with Native-like Mechanical Properties for Heart Valve Leaflet Tissue Engineering

Emerging technologies for cardiac tissue engineering and artificial hearts

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