Tri-Layered and Gel-Like Nanofibrous Scaffolds with Anisotropic Features for Engineering Heart Valve Leaflets

Shaohua Wu, Yiran Li, Caidan Zhang, Litao Tao, Mitchell Kuss, Jung Yul Lim, Jonathan Butcher, Bin Duan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

3D heterogeneous and anisotropic scaffolds that approximate native heart valve tissues are indispensable for the successful construction of tissue engineered heart valves (TEHVs). In this study, novel tri-layered and gel-like nanofibrous scaffolds, consisting of poly(lactic-co-glycolic) acid (PLGA) and poly(aspartic acid) (PASP), are fabricated by a combination of positive/negative conjugate electrospinning and bioactive hydrogel post-processing. The nanofibrous PLGA-PASP scaffolds present tri-layered structures, resulting in anisotropic mechanical properties that are comparable with native heart valve leaflets. Biological tests show that nanofibrous PLGA-PASP scaffolds with high PASP ratios significantly promote the proliferation and collagen and glycosaminoglycans (GAGs) secretions of human aortic valvular interstitial cells (HAVICs), compared to PLGA scaffolds. Importantly, the nanofibrous PLGA-PASP scaffolds are found to effectively inhibit the osteogenic differentiation of HAVICs. Two types of porcine VICs, from young and adult age groups, are further seeded onto the PLGA-PASP scaffolds. The adult VICs secrete higher amounts of collagens and GAGs and undergo a significantly higher level of osteogenic differentiation than young VICs. RNA sequencing analysis indicates that age has a pivotal effect on the VIC behaviors. This study provides important guidance and a reference for the design and development of 3D tri-layered, gel-like nanofibrous PLGA-PASP scaffolds for TEHV applications.

Original languageEnglish (US)
Article number2200053
JournalAdvanced Healthcare Materials
Volume11
Issue number10
DOIs
StatePublished - May 18 2022

Keywords

  • electrospinning
  • hydrogels
  • structural anisotropy
  • valve calcification
  • valve interstitial cells

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

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