Novel Biomimetic Coating for Circulatory Devices

描述(由申请人提供)： 循环和呼吸辅助装置，如体外循环电路(CPB)、脑室辅助装置(VAD)和血膜辅助装置(ECMO)是心脏手术中常用的辅助装置，用于支持患者受损的生理功能。接触患者血液的异物表面生物相容性不佳会导致血液蛋白分解系统的激活，如凝血、补体、纤溶等，还会激活细胞血液成分。这可能会导致潜在威胁生命的全身性炎症反应。BIOMEC开发了一种新型的、有前途的表面活性聚合物涂层(SPC)，可以用来显著提高这些设备的生物相容性。作为我们第二阶段SBIR工作的结果，BIOMEC改进了表面活性剂聚合物合成工艺，允许可重复生产大量广泛涂层和测试所需的材料。 比较了SPC涂层血泵与非涂层血泵(阴性对照)和肝素涂层血泵(阳性对照)在人体血液中的体外性能。我们证明，SPC防止表面血小板和中性粒细胞吸附的效果至少与肝素涂层相当，而且通常比肝素涂层更好。与肝素涂层泵相比，表面活性物质涂层还显著降低了溶血率。初步毒性测试和体内研究(猪模型)表明，涂层在生物上是安全的，不会影响泵的血流动力学性能。与肝素涂层相比，SPC的另一个优势是其在现有商业设备上的应用极其简单，因此成本较低。 在本项目阶段，我们建议按照FDA的要求继续对SPC进行生物安全性评价。此外，在批准研究设备豁免后，我们将进行一项试点临床研究，以最终证明SPC涂层体外循环电路在体内的安全性和有效性。作为这些努力的结果，BIOMEC将开发出一种用于血液接触设备的有效且廉价的血液兼容涂层。

DESCRIPTION (provided by applicant): Circulatory and respiratory assist devices, such as cardiopulmonary bypass circuits (CPB), ventricular assist devices (VAD's) and blood membrane (ECMO's) are routinely used in cardiac surgery and to support patient impaired physiological functions. Inadequate biocompatibility of foreign surfaces contacting the patient's blood contributes to the activation of blood proteolytic systems such as coagulation, complements, fibrinolysis and also activates cellular blood components. This can result in a potentially life threatening systemic inflammatory response. BIOMEC has developed a novel and promising type of surfactant polymer coating (SPC), which can be used to substantially improve the biocompatibility of these devices. As a result of our Phase II SBIR effort, BIOMEC has improved the process of surfactant polymer synthesis, which allows for reproducible production of larger volumes of the material necessary for extensive coating and testing. In vitro performance of SPC coated blood pumps in human blood was compared to the uncoated pumps (negative control) and to heparin coated pumps (positive control). We demonstrated that SPC prevents surface platelet and neutrophils adsorption with efficacy at least equivalent and generally better than heparin coating. The surfactant coating also significantly lowers the hemolysis rate in comparison to heparin-coated pumps. Preliminary toxicity testing and in vivo studies (pig model) indicate that the coating is biologically safe and does not affect the pump hemodynamic performance. An additional advantage of SPC over heparin coatings is its extreme simplicity of application to existing commercial devices, and hence its low cost. In this project phase we propose to continue biological safety evaluation of SPC according to FDA requirements. Further, upon approval of an Investigational Device Exemption we will conduct a pilot clinical study to conclusively demonstrate the in vivo safety and effectiveness of SPC coated cardiopulmonary bypass circuit. As the result of these efforts, BIOMEC will have developed an effective yet inexpensive blood compatible coating for blood contacting devices.