Use of arginine-glycine-aspartic acid adhesion peptides coupled with a new collagen scaffold to engineer a myocardium-like tissue graft.
BACKGROUND
Cardiac tissue engineering might be useful in treatment of diseased myocardium or cardiac malformations. The creation of functional, biocompatible contractile tissues, however, remains challenging. We hypothesized that coupling of arginine-glycine-aspartic acid-serine (RGD+) adhesion peptides would improve cardiomyocyte viability and differentiation and contractile performance of collagen-cell scaffolds.


METHODS
Clinically approved collagen scaffolds were functionalized with RGD+ cells and seeded with cardiomyocytes. Contractile performance, cardiomyocyte viability and differentiation were analyzed at days 1 and 8 and/or after culture for 1 month.


RESULTS
The method used for the RGD+ cell-collagen scaffold coupling enabled the following features: high coupling yields and complete washout of excess reagent and by-products with no need for chromatography; spectroscopic quantification of RGD+ coupling; a spacer arm of 36 A, a length reported as optimal for RGD+-peptide presentation and favorable for integrin-receptor clustering and subsequent activation. Isotonic and isometric mechanical parameters, either spontaneous or electrostimulated, exhibited good performance in RGD+ constructs. Cell number and viability was increased in RGD+ scaffolds, and we saw good organization of cell contractile apparatus with occurrence of cross-striation.


CONCLUSIONS
We report a novel method of engineering a highly effective collagen-cell scaffold based on RGD+ peptides cross-linked to a clinically approved collagen matrix. The main advantages were cell contractile performance, cardiomyocyte viability and differentiation.
Schussler
O
O
Biosurgical Research Laboratory, Georges Pompidou European Hospital, Paris V University, Paris, France. oschussler@ottawaheart.ca
Coirault
C
C
Louis-Tisserand
M
M
Al-Chare
W
W
Oliviero
P
P
Menard
C
C
Michelot
R
R
Bochet
P
P
Salomon
D R
DR
Chachques
J C
JC
Carpentier
A
A
Lecarpentier
Y
Y
D001672:Biocompatible Materials; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D003094:Collagen; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects*; D009842:Oligopeptides / Q000737:chemistry*; D023822:Tissue Engineering
D001672:Biocompatible Materials; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D003094:Collagen