van Lith Robert, Gregory Elaine K, Yang Jian, Kibbe Melina R, Ameer Guillermo A
Biomedical Engineering Department, Northwestern University, Evanston IL 60208, USA.
Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago IL 60611, USA; Institute for BioNanotechnology in Medicine, Northwestern University, Chicago IL 60611, USA.
Biomaterials. 2014 Sep;35(28):8113-22. doi: 10.1016/j.biomaterials.2014.06.004. Epub 2014 Jun 26.
Oxidative stress plays an important role in the limited biological compatibility of many biomaterials due to inflammation, as well as in various pathologies including atherosclerosis and restenosis as a result of vascular interventions. Engineering antioxidant properties into a material is therefore a potential avenue to improve the biocompatibility of materials, as well as to locally attenuate oxidative stress-related pathologies. Moreover, biodegradable polymers that have antioxidant properties built into their backbone structure have high relative antioxidant content and may provide prolonged, continuous attenuation of oxidative stress while the polymer or its degradation products are present. In this report, we describe the synthesis of poly(1,8-octanediol-co-citrate-co-ascorbate) (POCA), a citric-acid based biodegradable elastomer with native, intrinsic antioxidant properties. The in vitro antioxidant activity of POCA as well as its effects on vascular cells in vitro and in vivo were studied. Antioxidant properties investigated included scavenging of free radicals, iron chelation and the inhibition of lipid peroxidation. POCA reduced reactive oxygen species generation in cells after an oxidative challenge and protected cells from oxidative stress-induced cell death. Importantly, POCA antioxidant properties remained present upon degradation. Vascular cells cultured on POCA showed high viability, and POCA selectively inhibited smooth muscle cell proliferation, while supporting endothelial cell proliferation. Finally, preliminary data on POCA-coated ePTFE grafts showed reduced intimal hyperplasia when compared to standard ePTFE grafts. This biodegradable, intrinsically antioxidant polymer may be useful for tissue engineering application where oxidative stress is a concern.
氧化应激在许多生物材料因炎症导致的有限生物相容性中起着重要作用，在包括动脉粥样硬化和血管介入后再狭窄等各种病理状况中也发挥着作用。因此，将抗氧化性能引入材料是提高材料生物相容性以及局部减轻氧化应激相关病理状况的潜在途径。此外，主链结构中具有抗氧化性能的可生物降解聚合物具有较高的相对抗氧化剂含量，并且在聚合物或其降解产物存在时，可能会持续长时间地减轻氧化应激。在本报告中，我们描述了聚（1,8 - 辛二醇 - 共 - 柠檬酸 - 共 - 抗坏血酸）（POCA）的合成，这是一种基于柠檬酸的具有天然内在抗氧化性能的可生物降解弹性体。研究了POCA的体外抗氧化活性及其对体外和体内血管细胞的影响。所研究的抗氧化性能包括自由基清除、铁螯合和脂质过氧化抑制。POCA在氧化应激刺激后减少了细胞中活性氧的产生，并保护细胞免受氧化应激诱导的细胞死亡。重要的是，POCA在降解后仍保留抗氧化性能。在POCA上培养的血管细胞显示出高活力，并且POCA选择性地抑制平滑肌细胞增殖，同时支持内皮细胞增殖。最后，与标准ePTFE移植物相比，POCA涂层ePTFE移植物的初步数据显示内膜增生减少。这种可生物降解的、具有内在抗氧化性能的聚合物可能对关注氧化应激的组织工程应用有用。
