Abstract
Host remodeling is important for the success of medical implants, including vascular substitutes. Synthetic and tissue-engineered grafts have yet to show clinical effectiveness in arteries smaller than 5 mm in diameter. We designed cell-free biodegradable elastomeric grafts that degrade rapidly to yield neoarteries nearly free of foreign materials 3 months after interposition grafting in rat abdominal aorta. This design focuses on enabling rapid host remodeling. Three months after implantation, the neoarteries resembled native arteries in the following aspects: regular, strong and synchronous pulsation; a confluent endothelium and contractile smooth muscle layers; expression of elastin, collagen and glycosaminoglycan; and tough and compliant mechanical properties. Therefore, future studies employing large animal models more representative of human vascular regeneration are warranted before clinical translation. This cell-free approach represents a philosophical shift from the prevailing focus on cells in vascular tissue engineering and may have an impact on regenerative medicine in general.
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Acknowledgements
This research is supported by US National Institutes of Health (NIH) grant HL089658, American Heart Association award 0730031N and US NIH training grant 2T32HL076124. We thank S. Shroff for insightful discussions on mechanical testing of arteries, W. Wagner for access to the laser Doppler ultrasound and K. Kim for assistance with ultrasound imaging. We greatly appreciate R. Wagner and D. Rossi for performing angiography, M. Witt for DNA quantification, and D. Stolz, M. Sun and D. Clay for performing transmission electron microscopy.
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W.W. designed experiments, fabricated and implanted the grafts, characterized explants and analyzed data. R.A.A. performed mechanical characterization of grafts and explants, and analyzed data. Y.W. designed experiments and supervised the project. All authors interpreted results and contributed to writing the manuscript.
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Supplementary Table 1, Supplementary Figures 1–6 and Supplementary Methods (PDF 4922 kb)
Supplementary Video 1
Neo-artery pulses synchronously with host aorta (AVI 57182 kb)
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Wu, W., Allen, R. & Wang, Y. Fast-degrading elastomer enables rapid remodeling of a cell-free synthetic graft into a neoartery. Nat Med 18, 1148–1153 (2012). https://doi.org/10.1038/nm.2821
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DOI: https://doi.org/10.1038/nm.2821
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