TY - JOUR
T1 - Living nano-micro fibrous woven fabric/hydrogel composite scaffolds for heart valve engineering
AU - Wu, Shaohua
AU - Duan, Bin
AU - Qin, Xiaohong
AU - Butcher, Jonathan T.
N1 - Funding Information:
This work was funded by the American Heart Association Postdoctoral Fellowship (13POST17220071), The Hartwell Foundation, the National Science Foundation (CBET-0955172), Felton Family Endowment for Human Heart Valve Research at Seattle Children's Hospital, and the National Institutes of Health (HL118672, HL128745). This work was partly supported by Chang Jiang Youth Scholars Program of China and grants (51373033 and 11172064) from the National Natural Science Foundation of China, the Fundamental Research Funds for the Central Universities, DHU Distinguished Young Professor Program, and Key grant Project of Chinese Ministry of Education (No. 113027A) to Prof. X. Qin. This work was also supported by Chinese Universities Scientific Fund (CUSF-DH-D-2013021) and China Scholarship Council (CSC) to Dr. S. Wu. The authors thank Dr. Jonathan Chen in Seattle Children's Hospital and Sanjay Samy in Guthrie Clinic for providing human aortic valves. This work made use of the Cornell Center for Materials Research Facilities supported by the National Science Foundation under Award Number DMR-1120296. We would like to thank Cornell University Biotechnology Resource Center which is supported by National Institutes of Health (NIH 1S10RR025502-01) for the assistance with CLSM imaging.
Publisher Copyright:
© 2017 Acta Materialia Inc.
PY - 2017/3/15
Y1 - 2017/3/15
N2 - 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. Statement of Significance 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.
AB - 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. Statement of Significance 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.
KW - Fibroblastic phenotype
KW - Human aortic valve interstitial cells
KW - Nanofiber yarns
KW - Structure anisotropy
KW - Textile technique
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U2 - 10.1016/j.actbio.2017.01.051
DO - 10.1016/j.actbio.2017.01.051
M3 - Article
C2 - 28110071
AN - SCOPUS:85010495334
VL - 51
SP - 89
EP - 100
JO - Acta Biomaterialia
JF - Acta Biomaterialia
SN - 1742-7061
ER -