Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
J Biomed Mater Res A. 2021 Oct;109(10):1955-1966. doi: 10.1002/jbm.a.37188. Epub 2021 Jun 3.
A main problem in the design of blood-contacting biomaterials has been the deficiency of a systematic understanding of blood-biomaterial interactions and the strategy to modulate blood responses. In this work, different functional groups including carboxyl (COOH), hydroxyl (OH) and zwitterionic sulfobetaine group (⊕N((CH ) )(CH ) SO , SMDB) were grafted on the poly (butylene terephthalate) (PBT) film to study how the functional groups modulate blood responses and in terms of interaction with the coagulation system, the complement system, and platelets. The results showed protein absorption and platelet adhesion was stronger on the PBT bearing COOH group than PBT films bearing OH and zwitterionic sulfobetaine groups (total protein (μg/cm ): 32.92 ± 5.89 vs. 22.02 ± 1.44 vs. 19.09 ± 1.59; platelet adhesion (/mm ): 1,626.7 ± 120.1 vs. 1,395.6 ± 363.3 vs. 1,102.2 ± 373.7), which had a rougher and negatively charged surface, and the coagulation system was inhibited by binding fibrinogen (Fg) and coagulation factors. Meanwhile, PBT-PSMDB showed anticoagulant property and induced platelet activation. As a result, complement formation on these two films were less than PBT bearing OH groups by inhibiting the coagulation system (C3a (ng/ml): 3,745.4 ± 143.9 vs. 3,290.9 ± 249.7 vs. 4,887.9 ± 88.9; C5a (ng/ml): 22.1 ± 2.6 vs. 22.3 ± 1.8 vs. 27.9 ± 2.0). On the other hand, PBT bearing OH groups did not facilitate remarkable platelet adhesion and activation, and had no influence on platelet aggregation, hypotonic shock response, and coagulation system. The above results showed that the blood responses were highly interlinked, and could be modulated by grafting with different functional groups on the biomaterial surfaces. These findings may help identify a strategy to design materials with better hemocompatibility for blood contact, filtration, and purification applications.
在设计与血液接触的生物材料时，一个主要问题是缺乏对血液-生物材料相互作用的系统理解，以及对调节血液反应的策略。在这项工作中，不同的官能团，包括羧基（COOH）、羟基（OH）和两性离子磺基甜菜碱基团（⊕N((CH ) )(CH ) SO, SMDB），被接枝到聚对苯二甲酸丁二醇酯（PBT）薄膜上，以研究官能团如何调节血液反应，并从与凝血系统、补体系统和血小板相互作用的角度进行研究。结果表明，与带有 OH 和两性离子磺基甜菜碱基团的 PBT 薄膜相比，带有 COOH 基团的 PBT 薄膜上的蛋白质吸附和血小板黏附更强（总蛋白（μg/cm ）：32.92 ± 5.89 比 22.02 ± 1.44 比 19.09 ± 1.59；血小板黏附（/mm ）：1,626.7 ± 120.1 比 1,395.6 ± 363.3 比 1,102.2 ± 373.7），这是因为带有 COOH 基团的 PBT 薄膜表面更粗糙且带负电荷，并通过结合纤维蛋白原（Fg）和凝血因子抑制了凝血系统。同时，PBT-PSMDB 表现出抗凝血特性，并诱导血小板活化。因此，通过抑制凝血系统，这两种薄膜上补体的形成均少于带有 OH 基团的 PBT（C3a（ng/ml）：3,745.4 ± 143.9 比 3,290.9 ± 249.7 比 4,887.9 ± 88.9；C5a（ng/ml）：22.1 ± 2.6 比 22.3 ± 1.8 比 27.9 ± 2.0）。另一方面，带有 OH 基团的 PBT 不会促进明显的血小板黏附和活化，也不会影响血小板聚集、低渗休克反应和凝血系统。上述结果表明，血液反应高度相关，可以通过在生物材料表面接枝不同的官能团来调节。这些发现可能有助于确定一种设计具有更好血液相容性的材料的策略，用于血液接触、过滤和净化应用。
