Sutureless Microsurgical Anastomosis Using an Optimized Thermoreversible Intravascular Poloxamer Stent
Sutureless Microsurgical Anastomosis Using an Optimized Thermoreversible Intravascular Poloxamer Stent
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DOI：
10.1097/01.prs.0000475774.37267.3f
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发表时间：
2016-02-01
影响因子：
3.6
通讯作者：
Gurtner, Geoffrey C.
中科院分区：
文献类型：
--
作者：
Davis, Christopher R.;Rappleye, C. Travis;Gurtner, Geoffrey C.
背景：无缝线微血管吻合在简化微血管手术、缩短手术时间、改善临床预后方面具有巨大的转化潜力。作者开发了一种瞬时热可逆性微血管支架，在应用市购粘合剂密封吻合口而不是缝合之前，使用波洛沙姆维持血管腔通畅。尽管技术上取得了成功，但人类应用需要从现有配方中去除牛血清白蛋白；状态间的快速波洛沙姆转换；并增加了可靠的，可重复的，精确的微血管近似刚度。方法：本研究采用市售的两种poloxamer （P407和P188）。去除牛血清白蛋白后，以不同浓度单独或联合测试每种波洛沙姆，以确定无缝线微血管吻合的最佳制剂。通过流变学测试了转变温度和配方刚度，并在已建立的体内模型中测试了最有希望的组合。结果：波洛沙姆浓度的增加导致硬度增加，转变温度降低。不含牛血清白蛋白的纯P188，溶解在磷酸盐缓冲盐水中至45%的浓度，与我们之前的17% P407配方（96千帕对10千帕）相比，具有良好的流变学行为，具有精确的凝胶转变和更高的凝胶硬度。这些特性对于显微外科血管内使用是最佳的，根据手术控制的局部温度，提供手术精度和液体和固体状态之间的控制。结论：使用不含牛血清白蛋白的45% P188作为无缝线吻合的微血管支架具有最佳的流变学和平移特性。快速转换，增加的刚度和安全性证明了安全的转化应用于人体临床试验。
Background: Sutureless microvascular anastomosis has great translational potential to simplify microvascular surgery, shorten operative times, and improve clinical outcomes. The authors developed a transient thermoreversible microvascular stent using a poloxamer to maintain vessel lumen patency before application of commercially available adhesives to seal the anastomosis instead of sutures. Despite technical success, human application necessitates bovine serum albumin removal from existing formulations; rapid poloxamer transition between states; and increased stiffness for reliable, reproducible, and precise microvascular approximation.Methods: Two commercially available poloxamers were used in this study (P407 and P188). After removing bovine serum albumin, each poloxamer was tested at varying concentrations either alone or in combination to determine the optimal preparation for sutureless microvascular anastomosis. Transition temperature and formulation stiffness were tested in vitro by rheometry, with the most promising combinations tested in an established in vivo model.Results: Increasing poloxamer concentration resulted in an increase in stiffness and decrease in transition temperature. Pure P188 without bovine serum albumin, dissolved in phosphate-buffered saline to a 45% concentration, demonstrated desirable rheologic behavior, with precise gel transition and increased gel stiffness compared with our previous formulation of 17% P407 (96 kPa versus 10 kPa). These characteristics were optimal for microsurgical intravascular use, offering surgical precision and control between liquid and solid states, depending on the surgically controlled local temperature.Conclusions: Use of 45% P188 without bovine serum albumin demonstrated optimal rheologic and translational properties as a microvascular stent for sutureless anastomosis. Rapid transition, increased stiffness, and safety profile demonstrate safe translational application for human clinical trials.