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

Abstract

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

Sulfobetaine‐functionalized electrospun poly(ethylene‐co‐vinyl alcohol) membranes for blood filtration

“…The shifting of the OH peak in neat EVAL to higher wave numbers also hinted at functionalization with SMDB. These observations also agreed well with results from the literature …”

“…This hinted that the there was some sort of platelet activation caused by the bare EVAL; this prompted the platelets to extend their pseudopodia to hold the fiber surface. However, the hydration layer on the SMDB‐functionalized EVAL explicitly reduced the activation of platelets and, thus, ensured decreased platelet adhesion . Therefore, during the appraisal of the overall interactions by the SMDB‐functionalized EVAL membranes with the various blood components, the functionalized EVAL membranes showed a high RBC retention and WBC depletion for whole‐blood filtration compared to those of the neat EVAL membranes.…”

In vivo testing of the low-flow CO2 removal application of a compact, platform respiratory device

“…The entire ModELAS circuit is also uncoated, whereas most commercial artificial lung circuits are coated with a biocompatible coating [36,37]. Our laboratory is currently developing a tip-to-tip zwitterionic surface coating which will further improve hemocompatibility and further reduce thrombus formation within the ModELAS device, tubing, and catheter [38].…”

Artificial Lungs: Current Status and Future Directions

“…Accordingly, several groups are pursuing the development of novel thromboresistant coatings for implementation within artificial lungs. Novel approaches under investigation include the immobilization of zwitterionic molecules that mimic the exterior of cell membranes as well as the use of nitric oxide producing materials that inhibit platelet activation [38][39][40][41][42][43][44]. It should be noted that surface modification for improved hemocompatibility is a vast topic only briefly touched upon here but discussed more thoroughly elsewhere [45].…”