Biodegradable-Polymer-Blend-Based Surgical Sealant with Body-Temperature-Mediated Adhesion.
Biodegradable-Polymer-Blend-Based Surgical Sealant with Body-Temperature-Mediated Adhesion.
复制标题
DOI：
10.1002/adma.201503691
复制
发表时间：
2015-12-22
期刊：
影响因子：
--
通讯作者：
Kofinas P
中科院分区：
文献类型：
--
作者：
Behrens AM;Lee NG;Casey BJ;Srinivasan P;Sikorski MJ;Daristotle JL;Sandler AD;Kofinas P
目前许多方法利用仿生策略来促进组织粘附。这是通过使用在各种水生动物[7]和爬行动物中发现的反应性化学物质，成分或特征来实现的。[8]水生动物依靠化学粘合剂粘附在潮湿的表面上。例如，海洋贻贝使用含有邻苯二酚的后修饰氨基酸在氧化条件下共价结合胺和硫醇。[9]已经研究了这种官能化以原位形成水凝胶[10]和凝聚体的形式用于外科密封剂。[11]密封剂也被设计成通过模仿壁虎脚的高纵横比地形特征来最大化界面粘附。[8，12]这些微米和纳米图案化表面已与湿粘合剂化学品结合使用，以提高手术相关环境中的实用性。[13]开发外科密封剂的一个重要考虑因素是易用性。许多方法依赖于导致凝胶化或交联事件的混合和/或引发步骤。未能优化固化时间或溶液粘度等参数可能会导致应用装置堵塞或密封剂覆盖不足而导致性能差。剪切稀化水凝胶通过利用动态自组装来规避许多这些问题。[14]UV固化密封剂也引起了广泛的兴趣。[15]一种基于聚（甘油癸二酸酯丙烯酸酯）的快速固化疏水性光活化粘合剂最近在心脏手术中表现出有效性。[16]另一个有前途的策略是使用预成型的聚合物纳米片。[17]这些膜的纳米级厚度导致促进粘附的聚合物-基底相互作用。虽然有希望，但上述方法中的许多在几何上受到密封剂材料或施加装置的有限覆盖的限制。在这里，我们报告了体温激活的外科密封剂，利用可生物降解的聚合物共混物的热行为，以促进粘附。聚合物共混物使用称为溶液吹塑纺丝的技术用喷枪沉积。[18]该方法允许将聚合物纤维垫直接且快速地制造到任何感兴趣的解剖区域上。[19]在加热到临界温度（1031 ℃）后，由聚（乳酸-共-乙醇酸）（PLGA）/PEG共混物组成的纤维垫经历纤维垫到膜的转变。在该转变期间，密封剂的粘合强度增加并且变得透明。虽然PLGA和PEG的变体已被纳入可降解缝线[20]、外科结构[21]和止血敷料[22]中，但它们在这些应用中仅作为结构组分发挥作用，通常不会在自身的组织粘附中发挥积极作用。外科护理缺乏能够实现患者特定干预的材料。尽管存在技术限制，但传统的缝合和组织缝合仍然是外科组织闭合和密封的标准方法。[1]开发实用、高效和患者特异性的外科密封剂有可能提高手术能力并降低并发症的发生率。
Many current approaches utilize biomimetic strategies to promote tissue adhesion. This is accomplished through the use of reactive chemistries, components, or features found in a variety of aquatic animals [7] and reptiles.[8] Aquatic animals rely on adhesive chemistries to adhere to wet surfaces. For instance, marine mussels use a catechol containing posttranslationally modified amino acid to covalently bind to amines and thiols under oxidative conditions.[9] This functionalization has been investigated for use in surgical sealants in the form in situ forming hydrogels [10] and coacervates.[11] Sealants have also been designed to maximize interfacial adhesion by mimicking the high aspect ratio topographical features of gecko feet.[8, 12] These micro-and nanopatterned surfaces have been used in combination with wet adhesive chemistries to improve utility in a surgically relevant environment.[13] An important consideration in the development of surgical sealants is the ease of use. Many approaches rely on a mixing and/or an initiation step that leads to a gelation or crosslinking event. Failure to optimize parameters such as cure time or solution viscosity can lead to poor performance due to clogging of the application device or inadequate sealant coverage. Shear-thinning hydrogels circumvent many of these problems by taking advantage of dynamic self-assembly.[14] UV-curable sealants have also garnered wide interest.[15] A rapidly curing hydrophobic light-activated adhesive based on poly (glycerol sebacate acrylate) recently demonstrated efficacy in cardiac procedures.[16] Another promising strategy is the use of preformed polymer nanosheets.[17] The nanometer-scale thickness of these films results in polymer–substrate interactions that promote adhesion. While promising, many of the aforementioned approaches are geometrically restricted by the limited coverage of the sealant material or the application device. Here we report a body temperature activated surgical sealant that utilizes the thermal behavior of a biodegradable polymer blend to promote adhesion. The polymer blend is deposited with an airbrush using a technique called solution blow spinning.[18] This method allows for a polymer fiber mat to be directly and rapidly fabricated onto any anatomical region of interest.[19] After warming to a critical temperature (≈ 31 C), the fiber mat consisting of a poly (lactic-co-glycolic acid)(PLGA)/PEG blend undergoes a fiber mat to film transition. During this transition, the sealant increases in adhesive strength and becomes transparent. While variations of PLGA and PEG have been incorporated into degradable sutures,[20] surgical constructs,[21] and hemostatic dressings,[22] they only function as a structural component in these applications and do not typically take an active role in tissue adhesion on their own.Surgical care suffers from a lack of materials that enable patient specific intervention. Despite technical limitations, conventional suturing and tissue stapling remain the standard method of surgical tissue closure and sealing.[1] The development of practical, efficient, and patient specific surgical sealants has the potential to enhance surgical competency and reduce the incidence of complications.