Surgical ventricular restoration with a cell- and cytokine-seeded biodegradable scaffold.
Late after a myocardial infarction (MI), surgical ventricular restoration (SVR) can reduce left ventricular volumes, but an enhanced cardiac patch may be required to restore function. We developed a new, biodegradable patch (modified gelfoam, MGF) consisting of a spongy inner core (gelfoam) to encourage cell engraftment and an outer coating (poly epsilon-caprolactone) to provide sufficient strength to permit ventricular repair. Two weeks after coronary ligation in rats, SVR was performed using one of the following: gelfoam, MGF, MGF patches with hydrogel alone, or with hydrogel and cytokines (stem cell factor, stromal cell-derived factor-1alpha), bone marrow mesenchymal stem cells, or both. Cardiac function and morphology were evaluated by echocardiography, conduction catheterization, magnetic resonance imaging, and histology. Animals whose hearts were repaired with untreated gelfoam died of ventricular rupture. The MGF groups had significantly improved myocardial systolic function vs. MI controls. Enhancement with cytokines and/or cells promoted more alpha-smooth muscle actin-positive cells, more capillaries, greater wall thickness, a more ellipsoid shape, greater fractional shortening, and better-preserved systolic elastance than MGF alone. This combination of the new, reinforced, biodegradable biomaterial and cytokine/cell treatment created a viable tissue after SVR and produced better functional outcomes than un-reinforced gelfoam or MGF alone.
Miyagi
Yasuo
Y
Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network and the University of Toronto, Toronto, Ontario, Canada.
Zeng
Faquan
F
Huang
Xi-Ping
XP
Foltz
Warren D
WD
Wu
Jun
J
Mihic
Anton
A
Yau
Terrence M
TM
Weisel
Richard D
RD
Li
Ren-Ke
RK
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D016207:Cytokines / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D005781:Gelatin Sponge, Absorbable / Q000737:chemistry / Q000378:metabolism; D006352:Heart Ventricles / Q000473:pathology / Q000601:surgery; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000378:metabolism; D008422:Materials Testing; D015394:Molecular Structure; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery; D011091:Polyesters / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D016277:Ventricular Function, Left
D001672:Biocompatible Materials; D016207:Cytokines; D020100:Hydrogels; D011091:Polyesters; C016240:polycaprolactone