UCLA

Cerebrovascular ischemia from intracranial atherosclerosis remains difficult to treat. Current revascularization procedures, including intraluminal stents and extra cranial to intracranial bypass, have shown some benefit but are not without limitations due to high peri- and post- operative morbidity. We therefore developed a novel approach that involves gluing of arteries and subsequent transmural anastomosis from the healthy donor into the ischemic recipient. This approach required a new vascular sealant with distinct mechanical properties and adhesion which is not commercially available. We engineered an elastic glue based on functionalized elastin-like polypeptide (ELP) with methacryloyl groups (m-ELP) and fully characterized it in vitro. The select formulation attained desirable mechanics (elastic modulus: 288 � 19 kPa, extensibility: 34.5 � 13.4 %), adhesion (shear strength: 26.7 � 5.4 kPa), and biocompatibility (2D viability: 98 � 1 %). In addition, testing in an ex vivo porcine anastomosis model achieved burst pressure of 34.0 � 7.5 kPa, which is well over normal, elevated, and hypertensive crisis systolic blood pressures in humans at 16, 17.3, and 24 kPa respectively. Furthermore, a preliminary in vivo swine model assessed the feasibility of the two-glue sealant as well as the endovascular anastomosis application. The glue was applied and cross-linked at the anastomosis site under homeostatic conditions without difficulty. The anastomosis was created without bleeding complications and then confirmed by x-ray imaging. The procedure was well tolerated. Future studies will explore radio frequency ablation for creating the anastomosis, including how the hydrogel responds to temperature and humidity changes. Additional studies are needed to develop an algorithm to determine the size of the anastomosis unique to each patient. The formulation we developed is not limited in its uses. GelMA/m-ELP hydrogels can serve as sealants with remarkable elasticity and adhesion for vascular or pulmonary defects. Furthermore, the prepolymer solutions can be bioprinted or casted into functionalized scaffolds containing cells or drugs for tissue engineering and drug delivery systems.