title: Living nano-micro fibrous woven fabric/hydrogel composite scaffolds for heart valve engineering.
abstract: Regeneration and repair of injured or diseased heart valves remains a clinical challenge. Tissue engineering provides a promising treatment approach to facilitate living heart valve repair and regeneration. Three-dimensional (3D) biomimetic scaffolds that possess heterogeneous and anisotropic features that approximate those of native heart valve tissue are beneficial to the successful in vitro development of tissue engineered heart valves (TEHV). Here we report the development and characterization of a novel composite scaffold consisting of nano- and micro-scale fibrous woven fabrics and 3D hydrogels by using textile techniques combined with bioactive hydrogel formation. Embedded nano-micro fibrous scaffolds within hydrogel enhanced mechanical strength and physical structural anisotropy of the composite scaffold (similar to native aortic valve leaflets) and also reduced its compaction. We determined that the composite scaffolds supported the growth of human aortic valve interstitial cells (HAVIC), balanced the remodeling of heart valve ECM against shrinkage, and maintained better physiological fibroblastic phenotype in both normal and diseased HAVIC over single materials. These fabricated composite scaffolds enable the engineering of a living heart valve graft with improved anisotropic structure and tissue biomechanics important for maintaining valve cell phenotypes.
  
  
  
  Heart valve-related disease is an important clinical problem, with over 300,000 surgical repairs performed annually. Tissue engineering offers a promising strategy for heart valve repair and regeneration. In this study, we developed and tissue engineered living nano-micro fibrous woven fabric/hydrogel composite scaffolds by using textile technique combined with bioactive hydrogel formation. The novelty of our technique is that the composite scaffolds can mimic physical structure anisotropy and the mechanical strength of natural aortic valve leaflet. Moreover, the composite scaffolds prevented the matrix shrinkage, which is major problem that causes the failure of TEHV, and better maintained physiological fibroblastic phenotype in both normal and diseased HAVIC. This work marks the first report of a combination composite scaffold using 3D hydrogel enhanced by nano-micro fibrous woven fabric, and represents a promising tissue engineering strategy to treat heart valve injury.
authors.affiliation: Key Laboratory of Textile Science & Technology, Ministry of Education, College of Textiles, Donghua University, No. 2999 North Renmin Road, Songjiang, Shanghai 201620, China; Department of Biomedical Engineering, Cornell University, Ithaca, NY 14850, USA; Division of Cardiology, Department of Internal Medicine; Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY 14850, USA; Division of Cardiology, Department of Internal Medicine; Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Duan
authors.affiliation: Key Laboratory of Textile Science & Technology, Ministry of Education, College of Textiles, Donghua University, No. 2999 North Renmin Road, Songjiang, Shanghai 201620, China; Key Laboratory of Shanghai Micro & Nano Technology, Shanghai 201620, China. Electronic address: xhqin@dhu.edu.cn.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY 14850, USA. Electronic address: jtb47@cornell.edu.
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Butcher
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival; D060833:Cellular Microenvironment; D004247:DNA / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation; D006351:Heart Valves / Q000502:physiology*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D058628:Myofibroblasts / Q000166:cytology / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010012:Osteogenesis / Q000235:genetics; D010641:Phenotype; D013718:Tensile Strength; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D004247:DNA; D000469:Alkaline Phosphatase
keywords: Fibroblastic phenotype; Human aortic valve interstitial cells; Nanofiber yarns; Structure anisotropy; Textile technique