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(Circulation. 2002;106:I-176.)
© 2002 American Heart Association, Inc.

Thoracic Transplantation and Mechanical Support for Congestive Heart Failure

Optimal Biomaterial for Creation of Autologous Cardiac Grafts

Tsukasa Ozawa, MD, PhD; Donald A. G. Mickle, MD, MSc; Richard D. Weisel, MD; Nobuya Koyama, MD, PhD; Sumiko Ozawa, MD; Ren-Ke Li, MD, PhD

From the Department of Surgery, Division of Cardiovascular Surgery, Toronto General Research Institute, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.

Correspondence to Ren-Ke Li, MD, PhD, Toronto General Hospital, CCRW 1-815, 200 Elizabeth Street, Toronto, Ontario M5G 2C4 Canada. E-mail RenKeLi{at}uhnres.utoronto.ca

Abstract

Background The optimal cardiac graft for the repair of congenital heart defects will be composed of autologous cells and will grow with the child. The biodegradable material should permit rapid cellular growth and delayed degradation with minimal inflammation. We compared a new material, -caprolactone-co-L-lactide sponge reinforced with knitted poly-L-lactide fabric (PCLA), to gelatin (GEL) and polyglycolic acid (PGA), which are previously evaluated materials.

Methods Syngenic rat aortic smooth muscle cells (SMCs, 2x10⁶) were seeded onto GEL, PGA, and PCLA patches and cultured (n=11 per group). The DNA content in each patch was measured at 1, 2, and 3 weeks after seeding. Histological examination was performed 2 weeks after seeding. Cell-seeded patches were employed to replace a surgically created defect in the right ventricular outflow tract (RVOT) of rats (n=5 per group). Histology was studied at 8 weeks following implantation.

Results In vitro studies showed that the DNA content increased significantly (P<0.05) in all patches between 1 and 3 weeks after seeding. Histology and staining SMCs for anti--smooth muscle actin (SMA) revealed better growth of cells in the interstices of the grafts with GEL and PCLA than the PGA graft. In vivo studies demonstrated that seeded SMCs survived at least 8 weeks after the patch implantation in all groups. PCLA scaffolds were replaced by more cells with larger SMA-positive areas and by more extracellular matrix with larger elastin-positive areas than with GEL and PGA. The patch did not thin and expanded significantly. The GEL and PGA patches thinned and expanded. All grafts had complete endothelialization on the endocardial surface.

Conclusions SMC-seeded biodegradable materials can be employed to repair the RVOT. The novel PCLA patches permitted better cellular penetration in vitro and did not thin or dilate in vivo and did not produce an inflammatory response. The cell-seeded PCLA patch may permit the construction of an autologous patch to repair congenital heart defects.

Key Words: congenital cardiac defect • myocardium • tissue engineering • smooth muscle cells • biomaterials