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

Citation

Malkin, A. D.; Ye, S. H.; Lee, E. J.; Yang, X.; Zhu, Y.; Gamble, L. J.; Federspiel, W. J.; & Wagner, W. R. (2018). Development of zwitterionic sulfobetaine block copolymer conjugation strategies for reduced platelet deposition in respiratory assist devices. J Biomed Mater Res B Appl Biomater, 106(7), 2681-2692. PMCID: 6085169

Abstract

Respiratory assist devices, that utilize approximately 2 m(2) 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. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2681-2692, 2018.

Keyword(s)

*Membranes, Artificial
*Platelet Adhesiveness
Animals
Betaine/*analogs & derivatives/chemistry
Blood Platelets/*metabolism
Coated Materials, Biocompatible/*chemistry
Polycarboxylate Cement/chemistry
Polyvinyl Chloride/chemistry
Sheep

Notes

Malkin, Alexander D
Ye, Sang-Ho
Lee, Evan J
Yang, Xiguang
Zhu, Yang
Gamble, Lara J
Federspiel, William J
Wagner, William R
P41 EB002027/EB/NIBIB NIH HHS/
R01 HL089456/HL/NHLBI NIH HHS/
R01 HL117637/HL/NHLBI NIH HHS/
T32 HL076124/HL/NHLBI NIH HHS/
J Biomed Mater Res B Appl Biomater. 2018 Oct;106(7):2681-2692. doi: 10.1002/jbm.b.34085. Epub 2018 Feb 9.

Reference Type

Journal Article

Secondary Title

J Biomed Mater Res B Appl Biomater

Author(s)

Malkin, A. D.
Ye, S. H.
Lee, E. J.
Yang, X.
Zhu, Y.
Gamble, L. J.
Federspiel, W. J.
Wagner, W. R.

Year Published

2018

Date Published

1538352000

Volume Number

106

Issue Number

7

Pages

2681-2692

ISSN/ISBN

1552-4981 (Electronic)
1552-4973 (Linking)

DOI

10.1002/jbm.b.34085

PMCID

6085169