TY - JOUR
T1 - Integration of multiple cell-matrix interactions into alginate scaffolds for promoting cardiac tissue regeneration
AU - Sapir, Yulia
AU - Kryukov, Olga
AU - Cohen, Smadar
N1 - Funding Information: The research was supported by grants from the Israel Science Foundation ( 1368/08 ), the European Union FWP7 (INELPY) , and the Israel Ministry of Science, Culture and Sport . Yulia Sapir gratefully acknowledges the generous fellowship from Mr. Daniel Falkner (zl) and his daughter Ms. Ann Berger. Prof. Cohen holds the Claire and Harold Oshry Professor Chair in Biotechnology.
PY - 2011/3/1
Y1 - 2011/3/1
N2 - Cardiac tissue engineering aims to repair damaged myocardial tissues by applying heart patches created in vitro. Herein, we explored the possible role of a combination of two matrix-attached peptides, the adhesion peptide G4RGDY and heparin-binding peptide G4SPPRRARVTY (HBP) in cardiac tissue regeneration. Neonatal rat cardiac cells were seeded into unmodified, single peptide or double peptide-attached alginate scaffolds, all having the same physical features of porosity, hydrogel forming and matrix stiffness. The cardiac tissue developed in the HBP/RGD-attached scaffolds revealed the best features of a functional muscle tissue, as judged by all studied parameters, i.e., immunostaining of cardiac cell markers, histology, western blot of protein expressions and metabolic activity. By day 7, well-developed myocardial fibers were observed in these cell constructs. At 14 days the HBP/RGD-attached constructs presented an isotropic myofiber arrangement, while no such arrangement was seen in the other constructs. The expression levels of α-actinin, N-cadherin and Connexin-43, showing preservation and an increase in Connexin-43 expression (Cx-43) with time, further supported the formation a contractile muscle tissue in the HBP/RGD-attached scaffolds. Collectively, the attachment of combinatorial peptides representing different signaling in ECM-cell interactions proved to play a key role, contributing to the formation of a functional cardiac muscle tissue, in vitro.
AB - Cardiac tissue engineering aims to repair damaged myocardial tissues by applying heart patches created in vitro. Herein, we explored the possible role of a combination of two matrix-attached peptides, the adhesion peptide G4RGDY and heparin-binding peptide G4SPPRRARVTY (HBP) in cardiac tissue regeneration. Neonatal rat cardiac cells were seeded into unmodified, single peptide or double peptide-attached alginate scaffolds, all having the same physical features of porosity, hydrogel forming and matrix stiffness. The cardiac tissue developed in the HBP/RGD-attached scaffolds revealed the best features of a functional muscle tissue, as judged by all studied parameters, i.e., immunostaining of cardiac cell markers, histology, western blot of protein expressions and metabolic activity. By day 7, well-developed myocardial fibers were observed in these cell constructs. At 14 days the HBP/RGD-attached constructs presented an isotropic myofiber arrangement, while no such arrangement was seen in the other constructs. The expression levels of α-actinin, N-cadherin and Connexin-43, showing preservation and an increase in Connexin-43 expression (Cx-43) with time, further supported the formation a contractile muscle tissue in the HBP/RGD-attached scaffolds. Collectively, the attachment of combinatorial peptides representing different signaling in ECM-cell interactions proved to play a key role, contributing to the formation of a functional cardiac muscle tissue, in vitro.
KW - Cardiac tissue engineering
KW - ECM signaling
KW - Heparin-binding peptide
KW - RGD peptide
KW - Scaffold
KW - Syndecan
UR - http://www.scopus.com/inward/record.url?scp=78650996713&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2010.11.008
DO - 10.1016/j.biomaterials.2010.11.008
M3 - Article
SN - 0142-9612
VL - 32
SP - 1838
EP - 1847
JO - Biomaterials
JF - Biomaterials
IS - 7
ER -
