McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, 15219.
Departments of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, 15219.
J Biomed Mater Res B Appl Biomater. 2018 Oct;106(7):2681-2692. doi: 10.1002/jbm.b.34085. Epub 2018 Feb 9.
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.
呼吸辅助设备利用约 2 米长的中空纤维膜（HFMs）来实现所需的气体传递速率，但由于血液生物相容性的限制，其应用受到限制。本研究报告了两种技术，用于将两性离子磺基甜菜碱（SB）嵌段共聚物功能化并随后接枝到聚甲基戊烯（PMP）HFM 表面上，目的是减少呼吸辅助设备中的血栓形成。通过等离子体增强化学气相沉积对 PMP HFMs（PMP-A 或 PMP-H）进行胺或羟基功能化。生成的官能团与具有 N-羟基琥珀酰亚胺酯或硅氧烷基团的低分子量 SB 嵌段共聚物（SBNHS 或 SBNHSi）通过可逆加成-断裂链转移聚合进行接枝。改性 HFMs（PMP-A-SBNHS 或 PMP-H-SBNHSi）显示出从全绵羊血液中血小板沉积减少 80-95%，在预期操作条件下的流体剪切下稳定，并且相对于未改性 HFMs（PMP-C）气体交换性能不受抑制。此外，还表明功能化和 SBNHSi 接枝技术可减少聚碳酸酯和聚氯乙烯（两种常用于体外回路的其他材料）上的血小板沉积。观察到 SB 改性表面的抗血栓形成性和稳定性，而不会降低 HFM 的气体传递性能，表明该方法有望在呼吸辅助设备中进行更长时间的临床前测试，并最终允许减少长期接受支持的患者的抗凝水平。©2018Wiley Periodicals，Inc. J Biomed Mater Res Part B：Appl Biomater，106B：2681-2692，2018。
