Development of a biohybrid lung
Therapy for patients suffering from acute respiratory distress syndrome (ARDS) is substantially inadequate, resulting in a 40% mortality rate. A biohybrid lung prototype consisting of a rotating endothelialized microporous hollow fiber (MHF) bundle was studied as an alternative solution for improved patient outcome. It is hypothesized that endothelialized MHFs could present a surface mimicking the native vascular lining to reduce thrombotic deposition on underlying MHF. Such an approach might thus allow blood oxygenation and CO2 removal for extended periods with reduced anticoagulation requirements. Development of the biohybrid lung prototype, evaluation of endothelial cell (EC) response to shear stress, influence of endothelialization on gas transfer, and impact of bundle rotational speed on gas transfer and alterations in EC phenotype were studied.
MHFs were surface modified to promote EC attachment and proliferation. Endothelialized MHF bundles were rotated in the biohybrid lung prototype up to 1500 RPM (26.4 dynes/cm2). Blood-surface biocompatibility testing was performed on MHFs and MHF bundles in the biohybrid lung prototype, with or without ECs. Partial O2 pressures were recorded for blood samples to measure oxygen buildup within the biohybrid lung. Scanning electron micrographs (SEMs) of thrombotic deposition were taken. Upregulation of e-selectin and p-selectin on ECs were assessed for indication of an inflammatory EC phenotype.
ECs maintained near confluent coverage on MHFs under rotation at the tested speeds, and showed minimal p-selectin expression subsequent to rotation. It was observed that even low to moderate levels of EC coverage greatly reduced thrombotic deposition on MHFs. Statistically significant differences in oxygen accumulation between MHF bundles with or without endothelialization in the presence of 95% O2 were not found. Thrombotic deposition on endothelialized MHF bundles was less than or equivalent to thrombotic deposition on non-endothelialized MHF bundles following rotation. Low levels of e-selectin and p-selectin expression were observed following 24 hr hyperoxia.
These results suggest that endothelialized MHFs may serve to improve blood-surface biocompatibility in the presence of hyperoxia. Although further development and testing is required, a biohybrid lung employing endothelialized MHFs and a rotating fiber bundle may provide an alternative therapy for patients suffering from ARDS.
Advisor:William J. Federspiel; Harvey S. Borovetz; William R. Wagner; Donna Beer-Stolz; Bruce R. Pitt
School:University of Pittsburgh
School Location:USA - Pennsylvania
Source Type:Master's Thesis
Date of Publication:09/27/2006