Unal Gokberk, Jones Jesse, Baghdasarian Sevana, Kaneko Naoki, Shirzaei Sani Ehsan, Lee Sohyung, Gholizadeh Shima, Tateshima Satoshi, Annabi Nasim
Department of Chemical and Biomolecular Engineering University of California Los Angeles California USA.
Division of Interventional Neuroradiology David Geffen School of Medicine at UCLA Los Angeles California USA.
Bioeng Transl Med. 2021 Aug 10;6(3):e10240. doi: 10.1002/btm2.10240. eCollection 2021 Sep.
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.
颅内动脉粥样硬化引起的脑血管缺血仍然难以治疗。尽管目前的血管重建手术，包括腔内支架和颅外至颅内搭桥手术，已显示出一定益处，但它们存在围手术期和术后发病率。为解决这些局限性，我们在此开发了一种新方法，该方法涉及动脉粘贴以及随后从健康供体到缺血受体的穿壁吻合术。这种方法需要一种具有独特机械性能和粘附力的弹性血管密封剂来促进吻合。我们设计了两种水凝胶基胶水：一种基于甲基丙烯酰弹性蛋白样多肽（mELP）与甲基丙烯酰明胶（GelMA）结合的弹性复合水凝胶，以及一种基于纯GelMA的硬胶水。需要两种具有不同机械特性的配方来实现稳定的吻合。弹性GelMA/mELP复合胶水获得了理想的机械性能（弹性模量：288±19kPa，延伸率：34.5±13.4%）和对血管的粘附力（剪切强度：26.7±5.4kPa），而纯GelMA胶水表现出更高的粘附力（剪切强度：49.4±7.0kPa），代价是硬度增加（弹性模量：581±51kPa）和延伸率降低（13.6±2.5%）。体外生物相容性测试证实这些胶水无细胞毒性且可生物降解。此外，一个离体猪吻合模型显示出34.0±7.5kPa的高动脉破裂压力耐受性，远高于人类的正常收缩压（16kPa）、升高的收缩压（17.3kPa）和高血压危象收缩压（24kPa）。最后，使用体内猪模型评估使用新开发的双胶水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，且该手术耐受性良好。未来，需要更多研究来评估所开发密封剂在各种温度和湿度范围内的性能。
