A strongly adhesive hemostatic hydrogel for the repair of arterial and heart bleeds

Abstract

Uncontrollable bleeding is a major problem in surgical procedures and after major trauma. Existing hemostatic agents poorly control hemorrhaging from traumatic arterial and cardiac wounds because of their weak adhesion to wet and mobile tissues. Here we design a photo-reactive adhesive that mimics the extracellular matrix (ECM) composition. This biomacromolecule-based matrix hydrogel can undergo rapid gelling and fixation to adhere and seal bleeding arteries and cardiac walls after UV light irradiation. These repairs can withstand up to 290 mm Hg blood pressure, significantly higher than blood pressures in most clinical settings (systolic BP 60-160 mm Hg). Most importantly, the hydrogel can stop high-pressure bleeding from pig carotid arteries with 4~ 5 mm-long incision wounds and from pig hearts with 6 mm diameter cardiac penetration holes. Treated pigs survived after hemostatic treatments with this hydrogel, which is well-tolerated and appears to offer significant clinical advantage as a traumatic wound sealant.

Fig. 1

Chemical structure and mechanical properties of the hydrogels. a Constituent chemical structures and a schematic diagram illustrating the formation of the photo-triggered imine-crosslinked matrix hydrogel. b To monitor the gelling process, a dynamic time-sweep rheological analysis was carried out with an in situ photo-rheometer (HAAKE Mars III, light, Omnicure S2000 365 nm: 30 mW cm⁻²) showing the formation kinetics for GelMA/HA-NB/LAP, GelMA/HA-NB, and GelMA/LAP hydrogels. c The final torsion modulus G’ of different hydrogels. d The gel point of different hydrogels. All the gelling measurements were conducted using OmniCure S2000 (365 nm, 30 mW/cm²). Exposure time: 180 s for GelMA/HA-NB/LAP and GelMA hydrogels, and 300s for GelMA/HA-NB hydrogel (error bars, mean ± SD. ****p < 0.0001; NS: no significance, one-way analysis of variance (ANOVA), Tukey’s post hoc test) (n = 3 per group). Source data are available in the Source Data file

Fig. 2

Burst pressure of different hydrogels and surgical hemostatic glues. a Schematic illustration of the experimental procedure and pressure chamber for burst adhesion testing using a punctured, then sealed porcine sausage skin membrane. b The observed burst pressure of different hydrogels and the commercially available Cyanoacrylate and Fibrin Glue and Surgiflo^TM, a gelatin-based absorbable porcine gelatin paste used for hemostasis (error bars, mean ± SD; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, one-way analysis of variance (ANOVA), Tukey’s post hoc test) (n = 3 per group) Source data are available in the Source Data file

Fig. 3

Hemostatic properties of the matrix gel in a pig carotid artery damage model. a Schematic diagram of the surgical procedure. b Gross view of the rapid hemostasis and sealing in a pig carotid artery model. c The blood flow volumes through the pig’s carotid artery before and after surgery. d Macroscopic view of a healing hydrogel-covered carotid artery, 2 weeks after operating. e Postoperative tissue sections stained with hematoxylin–eosin, showing normal carotid artery (left) and the hydrogel-repaired vessels (right). Scale bar: 500 μm (left plates); 200 μm (right plates, enlarged) (n = 3) Source data are available in the Source Data file

Fig. 4

Hemostatic properties of the matrix gel in a pig cardiac puncture injury model. a Schematic diagram of the surgical procedure. b Gross view of the rapid hemostasis and sealing following cardiac puncture injury: the ventriculus sinister of the pig hearts was pierced by a 6 mm (inner diameter) needle, causing immediate high-pressure blood expulsion, subsequently continuing blood expulsion following needle removal. Then, the matrix gel was injected to cover the blood hole and rapidly irradiated with UV. After UV-induced rapid polymerization, the bleeding stopped completely within 10 s (four experimental operations were carried out). c Scanning electron micrographs of the interface between the pig heart puncture wound and the hydrogel. These sections derive from immediate postoperative autopsy on the heart of one pig, which was immediately killed after successful hemostatic treatment. Scale bar: 50 μm (left plates); 10 μm (right plates, enlarged). d Images of a heart autopsy following killing after two 2 weeks of postoperative recovery, the hydrogel still adhering to the wound, without any gap between gel and tissues, indicating continuous strong bonding at the healing interfaces. e Tissue staining images of the interface between pig heart cardiac tissue and the matrix gel, after 2 weeks of postoperative recovery. Scale bar: 200 μm (n = 4) Source data are available in the Source Data file

Fig. 5

Pre-and postoperative physiological indices in treated pigs. a Electrocardiogram (ECG) of a pig (No. 2) before and after surgery (1, 4, 7, and 14 days after treatment). b The heart rate of pigs before and after surgery. c The level of brain natriuretic peptide (BNP), before and after surgery (1, 4, 7, and 14 days after treatment). d Cardiac Troponin T (cTn-T), before and after surgery (1, 4, 7, and 14 days after treatment). e Aspartate aminotransferase (AST), f lactate dehydrogenase (LDH), g creatine kinase (CK), and h creatine kinase-MB (CK-MB) in the blood of pigs, sampled after their cardiac surgery (n = 3) Source data are available in the Source Data file