A Vascularized Three-dimensional Scaffold for Myocardial Infarct Repair
S. Kawamoto1, R. B. Vernon1, Q. Shi1, M. D. Gooden1, J. P. Flynn1, Y. Tabata2, M. D. Allen1.
1The Hope Heart Institute, Seattle, WA, 2Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
BACKGROUND: Cellular repair of myocardial infarcts requires that seeded cells survive in the ischemic infarct bed. A tissue engineering scaffold that provides angiogenic growth factors might accelerate host vascularization. We have developed a novel three-dimensional collagen gel incorporating microspheres that continuously release basic fibroblast growth factor (bFGF) over 7 days as a platform to support engineered cardiac replacement tissues.
METHODS: Gels constructed with 70 μm diameter hydrogel microspheres containing either bFGF (20 μg) or phosphate buffered saline (PBS controls) were cast into lenticular type I collagen gels. Gels were implanted subcutaneously in normal mice and excised 3, 7, or 14 days later. Vascular space was quantified as the area within CD31 (PECAM-1)-positive vascular profiles per high-powered field using image analysis software. Statistical analysis was by two-tailed t tests.
RESULTS: Accelerated neovascularization in the bFGF group was evident on both gross and histologic specimens by 7 and 14 days after implantation (Fig 1A,B) while no reaction was seen in PBS controls (C,D). At 7 days, vascular space in tissue surrounding the bFGF-containing collagen gels (11.8±0.62 %, n=7) was significantly greater than in the PBS-containing controls (0.89±0.39 %, n=7, p <0.0001).
CONCLUSIONS: Incorporating microspheres with timed release of bFGF into collagen gels resulted in a novel scaffold with significantly enhanced host neovascularization. Such a scaffold might improve the survival of seeded cardiac or skeletal myocytes in myocardial infarct areas.
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