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A multilayered valve leaflet promotes cell-laden collagen type I production and aortic valve hemodynamics.

ABSTRACT: Patients with aortic heart valve disease are limited to valve replacements that lack the ability to grow and remodel. This presents a major challenge for pediatric patients who require a valve capable of somatic growth and at a smaller size. A patient-specific heart valve capable of growth and remodeling while maintaining proper valve function would address this major issue. Here, we recreate the native valve leaflet structure composed of poly-ε-caprolactone (PCL) and cell-laden gelatin-methacrylate/poly (ethylene glycol) diacrylate (GelMA/PEGDA) hydrogels using 3D printing and molding, and then evaluate the ability of the multilayered scaffold to produce collagen matrix under physiological shear stress conditions. We also characterized the valve hemodynamics under aortic physiological flow conditions. The valve's fibrosa layer was replicated by 3D printing PCL in a circumferential direction similar to collagen alignment in the native leaflet, and GelMA/PEGDA sustained and promoted cell viability in the spongiosa/ventricularis layers. We found that collagen type I production can be increased in the multilayered scaffold when it is exposed to pulsatile shear stress conditions over static conditions. When the PCL component was mounted onto a valve ring and tested under physiological aortic valve conditions, the hemodynamics were comparable to commercially available valves. Our results demonstrate that a structurally representative valve leaflet can be generated using 3D printing and that the PCL layer of the leaflet can sustain proper valve function under physiological aortic valve conditions.

SUBMITTER: Nachlas ALY

PROVIDER: S-EPMC7190389 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe effect of different expressions of aortic valve disease on 3D aortic hemodynamics is unclear.PurposeTo investigate changes in aortic hemodynamics in patients with dilated ascending aorta (AAo) but different severity of aortic valve stenosis (AS) and/or regurgitation (AR).Study typeRetrospective.PopulationA total of 111 subjects (86 patients with AAo diameter ≥ 40 mm and 25 healthy controls, all with trileaflet aortic valve [TAV]). Patients were further stratified by TAV dysfunction: n = 9 with combined moderate or severe AS and AR (ASR, 56 ± 13 years), n = 14 with moderate or severe AS (AS, 64 ± 14 years), n = 33 with moderate or severe AR (AR, 62 ± 14 years), n = 30 with neither AS nor AR (no AS/AR, 63 ± 9 years).Field strength/sequence4D flow MRI on 1.5/3T systems for the in vivo analysis of aortic blood flow dynamics.AssessmentData analysis included grading of 3D AAo vortex/helix flow and AAo flow eccentricity as well as quantification of systolic peak velocities and wall shear stress (WSS).Statistical testsContinuous variables were compared by one-way analysis of variance or Kruskal-Wallis, followed by a pairwise Tukey or Dunn test if there was a significant difference.ResultsAll patients demonstrated markedly elevated vortex and helix flow compared with controls (P < 0.05). Peak velocities were significantly elevated in ASR, AS, and AR patients compared with controls (P < 0.05). Increased flow eccentricity was observed in entire AAo for AR, at the mid and distal AAo for ASR and AS, and at the proximal AAo for no AS/AR. Compared with controls, WSS in the AAo was significantly elevated in ASR and AS patients (P < 0.05) and reduced in no AS/AR patients (P < 0.05).Data conclusionThe presence of TAV dysfunction is associated with aberrant hemodynamics and altered WSS, which may play a role in the development of aortopathy.Level of evidence3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:481-491.

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A multilayered valve leaflet promotes cell-laden collagen type I production and aortic valve hemodynamics.

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