Tissue Engineering of an Implantable Bioartificial Hemofilter

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Abstract

The first step in the tissue engineering of an implantable bioartificial kidney is the development of an implant that produces ultrafiltrate to replace glomerular function. A fabricated device containing synthetic hollow hemofiltration fibers was placed around the femoral vascular pedicle in rats, which initiated new tissue formation with a mature and durable neocapillary bed. The transudate fluid produced by this newly formed capillary bed accumulated through the hollow fibers into a subcutaneous port to allow evaluation of the fluid. In its first phase, this study evaluated various hollow fibers and tissue induction processes by the measurement of fluid volume, urea nitrogen, and total protein continuously for 6 weeks. New tissues formed within the implants surrounding the fibers, and the vascular density, vessel sizes, and percent cross-sectional vascular area were assessed by means of histomorphometric analysis after 6 weeks. The volume of fluid formation correlated with both vascular density and fiber membrane surface area. The implant fluid-to-serum ratios demonstrated a permselective filtrate. In a second phase, platelet-derived growth factor and vascular endothelial growth factor versus carrier alone were infused directly into the implants for the first 4 weeks in vivo through osmotic pumps and followed up to 9 weeks. Cumulative implant fluid volumes were significantly greater in the growth factor–treated group than in control animals and were associated with greater numbers of small-caliber blood vessels. These results provide the initial proof of concept in developing a tissue-engineered hemofilter prototype on a small scale in a rodent model.

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