We hypothesize that a combinatorial approach of ventricle constraint and stem cell therapy would offer a greater benefit for the treatment of heart failure than either strategy alone. A heart patch would serve two therapeutic purposes: biomechanical support and cell delivery. In this study, we describe a hybrid heart patch engineered from a synthetic elastomer, poly(glycerol sebacate) (PGS), supplemented with cardiomyocytes differentiated from human embryonic stem cells (hESCs). In line with two therapeutically relevant considerations, i.e. biocompatibility and cell delivery efficiency, the PGS was (a) pre-conditioned in culture medium for 6 days, and (b) prepared without gelatin coatings to facilitate detachment and delivery of cardiomyocytes following patch implantation. Following pre-conditioning under physiological conditions, the PGS patch material without gelatin coating was found to satisfactorily support cardiomyocyte viability and attachment, with active cell beating for periods of longer than 3 months until interrupted. Dynamic culture studies revealed that cells detached more efficiently from the uncoated surface of PGS than from gelatin-coated PGS. No significant differences were detected between the beating rates of human embryonic stem cell-derived cardiomyocytes on tissue culture plate and the pre-conditioned and gelatin-uncoated PGS. PGS patches sutured over the left ventricle of rats in vivo remained intact over a 2 week period without any deleterious effects on ventricular function. We conclude that PGS is a suitable biomaterial for stem cell-based regeneration strategies to restore cardiomyocyte function, and the hybrid heart patch engineered under optimal conditions would be a promising support device for the cardiac repair.
An elastomeric patch derived from poly(glycerol sebacate) for delivery of embryonic stem cells to the heart
Year: 2010
Journal: Biomaterials, Volume 31, Issue 14, May 2010, Pages 3885-3893, 20111221
Authors: Qi-Zhi Chen a, Hikaru Ishii b , George A. Thouas c , Alexander R. Lyon b , Jamie S. Wright b , Jonny J. Blaker d , Wojciech Chrzanowski e , Aldo R. Boccaccini f , Nadire N. Ali b , Jonathan C. Knowles e , Siaˆn E. Harding b
Organizations: a Department of Materials Engineering, Monash University, Clayton, VIC 3800, Australia, b National Heart and Lung Institute, Imperial College London, Flowers Building, 4th Floor, Armstrong Road, London SW7 2AZ, UK, c Division of Biological Engineering, Monash University, Clayton, VIC 3800, Australia, d Department of Chemical Engineering, Polymer & Composite Engineering (PaCE) Group, Imperial College London, London, SW7 2AZ, UK,e Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, University College London, 256 Gray’s Inn Road, London WC1X 8LD, UK, f Department of Materials, Imperial College London, Prince Consort Road, London SW7 2AZ, UK