Abstract
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.