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J Biomed Mater Res B Appl Biomater. 2018 Oct;106(7):2681-2692. doi: 10.1002/jbm.b.34085. Epub 2018 Feb 9.

Development of zwitterionic sulfobetaine block copolymer conjugation strategies for reduced platelet deposition in respiratory assist devices.

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McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, 15219.
Departments of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, 15219.
Departments of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, 15219.
Department of Bioengineering and NESAC/BIO, University of Washington, Seattle, Washington, 98195.
Departments of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, 15219.
Departments of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, 15219.


Respiratory assist devices, that utilize ∼2 m2 of hollow fiber membranes (HFMs) to achieve desired gas transfer rates, have been limited in their adoption due to such blood biocompatibility limitations. This study reports two techniques for the functionalization and subsequent conjugation of zwitterionic sulfobetaine (SB) block copolymers to polymethylpentene (PMP) HFM surfaces with the intention of reducing thrombus formation in respiratory assist devices. Amine or hydroxyl functionalization of PMP HFMs (PMP-A or PMP-H) was accomplished using plasma-enhanced chemical vapor deposition. The generated functional groups were conjugated to low molecular weight SB block copolymers with N-hydroxysuccinimide ester or siloxane groups (SBNHS or SBNHSi) that were synthesized using reversible addition fragmentation chain transfer polymerization. The modified HFMs (PMP-A-SBNHS or PMP-H-SBNHSi) showed 80-95% reduction in platelet deposition from whole ovine blood, stability under the fluid shear of anticipated operating conditions, and uninhibited gas exchange performance relative to non-modified HFMs (PMP-C). Additionally, the functionalization and SBNHSi conjugation technique was shown to reduce platelet deposition on polycarbonate and poly(vinyl chloride), two other materials commonly found in extracorporeal circuits. The observed thromboresistance and stability of the SB modified surfaces, without degradation of HFM gas transfer performance, indicate that this approach is promising for longer term pre-clinical testing in respiratory assist devices and may ultimately allow for the reduction of anticoagulation levels in patients being supported for extended periods.


gas transfer performance; reduction of thrombus formation; respiratory assist devices; surface functionalization and conjugation; zwitterionic sulfobetaine block copolymers

[Available on 2019-10-01]

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