Electrospun PGS:PCL microfibers align human valvular interstitial cells and provide tunable scaffold anisotropy.
Tissue engineered heart valves (TEHV) can be useful in the repair of congenital or acquired valvular diseases due to their potential for growth and remodeling. The development of biomimetic scaffolds is a major challenge in heart valve tissue engineering. One of the most important structural characteristics of mature heart valve leaflets is their intrinsic anisotropy, which is derived from the microstructure of aligned collagen fibers in the extracellular matrix (ECM). In the present study, a directional electrospinning technique is used to fabricate fibrous poly(glycerol sebacate):poly(caprolactone) (PGS:PCL) scaffolds containing aligned fibers, which resemble native heart valve leaflet ECM networks. In addition, the anisotropic mechanical characteristics of fabricated scaffolds are tuned by changing the ratio of PGS:PCL to mimic the native heart valve's mechanical properties. Primary human valvular interstitial cells (VICs) attach and align along the anisotropic axes of all PGS:PCL scaffolds with various mechanical properties. The cells are also biochemically active in producing heart-valve-associated collagen, vimentin, and smooth muscle actin as determined by gene expression. The fibrous PGS:PCL scaffolds seeded with human VICs mimick the structure and mechanical properties of native valve leaflet tissues and would potentially be suitable for the replacement of heart valves in diverse patient populations.
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 65 Landsdowne Street, Cambridge, MA, 02139, USA; Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, MA, 02115, USA; Department of Cardiac, Surgery Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA; Department of Bioengineering, The Pennsylvania State University, 205 Hallowell Building, State College, PA, 16801, USA.
Nafiseh
N
Masoumi
Benjamin L
BL
Larson
Nasim
N
Annabi
Mahshid
M
Kharaziha
Behnam
B
Zamanian
Kayle S
KS
Shapero
Alexander T
AT
Cubberley
Gulden
G
Camci-Unal
Keefe B
KB
Manning
John E
JE
Mayer
Ali
A
Khademhosseini
D000199:Actins / Q000378:metabolism; D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003651:Decanoates / Q000737:chemistry*; D055119:Elastic Modulus; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005990:Glycerol / Q000031:analogs & derivatives* / Q000737:chemistry; D006351:Heart Valves / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D011091:Polyesters / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D013552:Swine; D013718:Tensile Strength; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014746:Vimentin / Q000378:metabolism
C541116:ACTA2 protein, human; D000199:Actins; D003651:Decanoates; D011091:Polyesters; D011108:Polymers; D014746:Vimentin; C469892:poly(glycerol-sebacate); C016240:polycaprolactone; D003094:Collagen; D005990:Glycerol
aortic valve; electrospinning; human valvular interstitial cells; mechanical properties; tissue engineered heart valve