Cerebrovascular ischemia from intracranial atherosclerosis remains difficult to treat. Although current revascularization procedures, including intraluminal stents and extracranial to intracranial bypass, have shown some benefit, they suffer from perioperative and postoperative morbidity. To address these limitations, here we developed a novel approach that involves gluing of arteries and subsequent transmural anastomosis from the healthy donor into the ischemic recipient. This approach required an elastic vascular sealant with distinct mechanical properties and adhesion to facilitate anastomosis. We engineered two hydrogel-based glues: an elastic composite hydrogel based on methacryloyl elastin-like polypeptide (mELP) combined with gelatin methacryloyl (GelMA) and a stiff glue based on pure GelMA. Two formulations with distinct mechanical characteristics were necessary to achieve stable anastomosis. The elastic GelMA/mELP composite glue attained desirable mechanical properties (elastic modulus: 288 ± 19 kPa, extensibility: 34.5 ± 13.4%) and adhesion (shear strength: 26.7 ± 5.4 kPa) to the blood vessel, while the pure GelMA glue exhibited superior adhesion (shear strength: 49.4 ± 7.0 kPa) at the cost of increased stiffness (elastic modulus: 581 ± 51 kPa) and reduced extensibility (13.6 ± 2.5%). The in vitro biocompatibility tests confirmed that the glues were not cytotoxic and were biodegradable. In addition, an ex vivo porcine anastomosis model showed high arterial burst pressure resistance of 34.0 ± 7.5 kPa, which is well over normal (16 kPa), elevated (17.3 kPa), and hypertensive crisis (24 kPa) systolic blood pressures in humans. Finally, an in vivo swine model was used to assess the feasibility of using the newly developed two-glue system for an endovascular anastomosis. X-ray imaging confirmed that the anastomosis was made successfully without postoperative bleeding complications and the procedure was well tolerated. In the future, more studies are required to evaluate the performance of the developed sealants under various temperature and humidity ranges.

中文翻译：

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基于明胶和类弹性蛋白多肽的工程弹性密封剂用于血管内吻合术


颅内动脉粥样硬化引起的脑血管缺血仍然难以治疗。尽管目前的血运重建手术，包括腔内支架和颅外至颅内旁路，已显示出一些益处，但它们存在围手术期和术后发病率。为了解决这些限制，我们在这里开发了一种新方法，包括将动脉粘合并随后从健康供体到缺血​​受体进行透壁吻合。这种方法需要具有独特机械性能和粘附力的弹性血管密封剂以促进吻合。我们设计了两种基于水凝胶的胶水：基于甲基丙烯酰弹性蛋白样多肽（mELP）与甲基丙烯酰明胶（GelMA）相结合的弹性复合水凝胶和基于纯GelMA的硬胶。要实现稳定的吻合，需要两种具有不同机械特性的配方。弹性GelMA/mELP复合胶获得了理想的机械性能（弹性模量：288±19kPa，延伸性：34.5±13.4%）和对血管的粘附力（剪切强度：26.7±5.4kPa），而纯GelMA胶表现出优越的性能。粘合力（剪切强度：49.4 ± 7.0 kPa），但代价是刚度增加（弹性模量：581 ± 51 kPa）和延展性降低（13.6 ± 2.5%）。体外生物相容性测试证实该胶水不具有细胞毒性且可生物降解。此外，离体猪吻合模型显示出34.0±7.5 kPa的高动脉爆裂压阻力，远高于人类正常收缩压（16 kPa）、升高收缩压（17.3 kPa）和高血压危象收缩压（24 kPa）。 最后，利用猪体内模型来评估使用新开发的双胶系统进行血管内吻合的可行性。 X射线成像证实吻合成功，无术后出血并发症，手术耐受性良好。未来，需要更多的研究来评估所开发的密封剂在不同温度和湿度范围下的性能。