Novel Biomimetic Coating for Circulatory Devices

描述（由申请人提供）： 循环和呼吸辅助装置，例如心肺旁路回路（CPB）、心室辅助装置（VAD）和血膜（ECMO）常规用于心脏手术中，并用于支持患者受损的生理功能。接触患者血液的外来表面的生物相容性不足有助于激活血液蛋白水解系统，例如凝血、补体、纤维蛋白溶解，并且还激活细胞血液成分。这可能导致潜在的危及生命的全身炎症反应。BIOMEC开发了一种新型且有前途的表面活性剂聚合物涂层（SPC），可用于大幅改善这些器械的生物相容性。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的合成工艺，这使得可重复生产大量广泛涂层和测试所需的材料。 将SPC涂层血泵在人体血液中的体外性能与无涂层泵（阴性对照）和肝素涂层泵（阳性对照）进行比较。我们证明SPC防止表面血小板和中性粒细胞吸附的功效至少等同于并且通常优于肝素涂层。与肝素涂层泵相比，表面活性剂涂层还显著降低了溶血率。初步毒性试验和体内研究（猪模型）表明，涂层具有生物安全性，不会影响泵的血流动力学性能。SPC优于肝素涂层的另一个优点是其应用于现有商业器械的极端简单性，因此其成本低。 在本项目阶段，我们建议根据FDA要求继续进行SPC的生物安全性评价。此外，在试验用器械豁免获得批准后，我们将开展一项初步临床研究，以最终证明SPC涂层心肺转流回路的体内安全性和有效性。通过这些努力，BIOMEC将开发出一种有效且廉价的血液相容性涂层，用于血液接触装置。

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.