"Synthetic vascular grafts perform very poorly in small diameter applications (coronary/peripheral bypass) and for dialysis access. Better vascular conduits for these applications would be life and limb-saving for a very large patient population. A biological, human, tissue-engineered blood vessel (TEBV) may be such a device. We have developed a method to produce robust sheets of cell-assembled extracellular matrix (CAM) from normal, adult, human fibroblasts in vitro. These have been rolled into TEBV and shown promising clinical results. However, this initial rolling approach is very costly, time consuming and has limited mechanical design potential. Here, we propose a new textile-based assembly method that can lift all these limitations.
Task#1 will aim at processing CAM sheets into various types of yarns (human and large animal) and characterizing composition, organization, and mechanical properties. Task#2 will aim at quantifying the in vivo remodeling of the various yarns in nude rats (human yarn) and in an allogeneic recipient (large animal) as subcutaneous implants. This screening process will identify yarns with the best biological response and mechanical profiles. Task#3 will aim at weaving human and animal, non-living, TEBVs with clinically relevant biological and mechanical properties. Task#4 will evaluate the long-term (1 year) performance of the animal TEBV in an allogeneic setting.
This study will provide:
1) in-depth understanding of the immune reactivity of this CAM, both from the innate and specific immune system.
2) long-term performance data of a woven, CAM-based, TEBV in an allogeneic setting (animal).
3) a human woven TEBV with clinically relevant mechanical properties ready for in vivo testing.
This “next generation” assembly method will reduce TEBV production time/cost 3-fold and represents a more versatile, reliable and highly tunable approach. HUMAN TEXTILES will provide a COMPLETELY NEW TYPE OF SCAFFOLD for engineering a variety of organs."
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