Department of Chemistry, ‡School of Biomedical Engineering, and §Department of Chemical & Biological Engineering, Colorado State University , Fort Collins, Colorado 80523, United States.
ACS Appl Mater Interfaces. 2017 Jan 25;9(3):2104-2113. doi: 10.1021/acsami.6b12888. Epub 2017 Jan 9.
Nitric oxide (NO) occurs naturally in mammalian biochemistry as a critical signaling molecule and exhibits antithrombotic, antibacterial, and wound-healing properties. NO-forming biodegradable polymers have been utilized in the development of antithrombotic or antibacterial materials for biointerfacial applications, including tissue engineering and the fabrication of erodible coatings for medical devices such as stents. Use of such NO-forming polymers has frequently been constrained by short-term release or limited NO storage capacity and has led to the pursuit of new materials with improved NO release function. Herein, we report the development of an NO-releasing bioerodible coating prepared from poly[bis(3-mercapto-3-methylbut-1-yl glycinyl)phosphazene] (POP-Gly-MMB), a polyphosphazene based on glycine and the naturally occurring tertiary thiol 3-mercapto-3-methylbutan-1-ol (MMB). To evaluate the NO release properties of this material, the thiolated polymer POP-Gly-MMB-SH was applied as a coating to glass substrates and subsequently converted to the NO-forming S-nitrosothiol (RSNO) derivative (POP-Gly-MMB-NO) by immersion in a mixture of tert-butyl nitrite (t-BuONO) and pentane. NO release flux from the coated substrates was determined by chemiluminescence-based NO measurement and was found to remain in a physiologically relevant range for up to 2 weeks (6.5-0.090 nmol of NO·min·cm) when immersed in pH 7.4 phosphate-buffered saline (PBS) at 37 °C. Furthermore, the coating exhibited an overall NO storage capacity of 0.89 ± 0.09 mmol·g (4.3 ± 0.6 μmol·cm). Erosion of POP-Gly-MMB-NO in PBS at 37 °C over 6 weeks results in 14% mass loss, and time-of-flight mass spectrometry (TOF-MS) was used to characterize the organic products of hydrolytic degradation as glycine, MMB, and several related esters. The comparatively long-term NO release and high storage capacity of POP-Gly-MMB-NO coatings suggest potential as a source of therapeutic NO for biomedical applications.
一氧化氮（NO）在哺乳动物生物化学中作为一种关键的信号分子自然存在，并表现出抗血栓、抗菌和促进伤口愈合的特性。可形成一氧化氮的生物降解聚合物已被用于开发用于生物界面应用的抗血栓或抗菌材料，包括组织工程和可生物降解涂层的制造，例如支架等医疗设备。然而，此类可形成一氧化氮的聚合物的使用经常受到短期释放或有限的一氧化氮储存能力的限制，并导致了对具有改进的一氧化氮释放功能的新材料的追求。在此，我们报告了一种由聚[双（3-巯基-3-甲基丁基甘氨酰基）磷腈]（POP-Gly-MMB）制备的可释放一氧化氮的生物可侵蚀涂层的开发，POP-Gly-MMB 是一种基于甘氨酸和天然叔硫醇 3-巯基-3-甲基丁醇（MMB）的聚磷腈。为了评估该材料的一氧化氮释放特性，将疏硫聚合物 POP-Gly-MMB-SH 涂覆在玻璃基底上，然后将其浸入叔丁基亚硝化物（t-BuONO）和戊烷的混合物中转化为形成一氧化氮的 S-亚硝基硫醇（RSNO）衍生物（POP-Gly-MMB-NO）。通过基于化学发光的一氧化氮测量来确定涂覆基底的一氧化氮释放通量，并发现当在 37°C 的 pH7.4 磷酸盐缓冲盐水（PBS）中浸泡时，在长达 2 周的时间内（6.5-0.090nmol 的 NO·min·cm）仍保持在生理相关范围内。此外，该涂层的总一氧化氮储存能力为 0.89±0.09mmol·g（4.3±0.6μmol·cm）。在 37°C 的 PBS 中，POP-Gly-MMB-NO 的侵蚀在 6 周内导致 14%的质量损失，并且使用飞行时间质谱（TOF-MS）来表征水解降解的有机产物为甘氨酸、MMB 和几种相关的酯。POP-Gly-MMB-NO 涂层具有相对较长的一氧化氮释放时间和高储存能力，这表明其在生物医学应用中作为治疗性一氧化氮的来源具有潜力。
