Tissue adhesives do not normally perform well on tissues that are covered with blood or other bodily fluids. Here we report the design, adhesion mechanism and performance of a paste that haemostatically seals tissues in less than 15 s, independently of the blood-coagulation rate. With a design inspired by barnacle glue (which strongly adheres to wet and contaminated surfaces owing to adhesive proteins embedded in a lipid-rich matrix), the paste consists of a blood-repelling hydrophobic oil matrix containing embedded microparticles that covalently crosslink with tissue surfaces on the application of gentle pressure. It slowly resorbs over weeks, sustains large pressures (approximately 350 mm Hg of burst pressure in a sealed porcine aorta), makes tough (interfacial toughness of 150–300 J m−2) and strong (shear and tensile strengths of, respectively, 40–70 kPa and 30–50 kPa) interfaces with blood-covered tissues, and outperforms commercial haemostatic agents in the sealing of bleeding porcine aortas ex vivo and of bleeding heart and liver tissues in live rats and pigs. The paste may aid the treatment of severe bleeding, even in individuals with coagulopathies.
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Lyophilized apoptotic vesicle-encapsulated adhesive hydrogel sponge as a rapid hemostat for traumatic hemorrhage in coagulopathy
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We thank the Koch Institute Swanson Biotechnology Center for technical support, specifically K. Cormier and the Histology Core for the histological processing, and R. Bronson at Harvard Medical School for the histological evaluations. This work is supported by the MIT Deshpande Center (H.Y., C.S.N., X.Z.), National Institutes of Health (1-R01-HL153857-01, X.Z.), National Science Foundation (EFMA-1935291, X.Z.), the US Army Research Office through the Institute for Soldier Nanotechnologies at MIT (W911NF-13-D-0001) and the ZOLL Foundation (C.S.N.). H.Y. acknowledges financial support from Samsung Scholarship.
H.Y., X.M., C.S.N. and X.Z. are named as inventors on a patent application (US no. 62/942,874) that covers the design and repel–crosslinking mechanism of the barnacle-glue-inspired paste.
Peer review information Nature Biomedical Engineering thanks Nasim Annabi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Extended Data Fig. 1 Overall process of rapid haemostatic tissue sealing by the barnacle-glue-inspired paste.
(Step 1 and 2) The barnacle-glue-inspired paste can be applied directly on bleeding injury without any other preparation process; (Step 3 and 4) On application of gentle pressure, the silicone oil matrix in the barnacle-glue-inspired paste repels and clean blood from the bleeding injury; (Step 5 and 6) Simultaneously, the carboxylic acid groups in the bioadhesive microparticles form temporary physical crosslinks by hydrogen bonds, followed by the covalent crosslinking between the NHS ester groups and the primary amine groups with themselves and the tissue surfaces; (Step 7) the swollen and crosslinked paste provides robust haemostatic tissue sealing.
a, Schematic illustrations for the physical crosslinking-based adhesion between the barnacle-glue-inspired paste and the tissue surface. b, Schematic illustrations for the covalent crosslinking-based adhesion between the barnacle-glue-inspired paste and the tissue surface. c, Interfacial toughness of blood-covered porcine skin adhered by the paste with and without NHS ester over time. Values in c represent the mean and the standard deviation (n = 3; independent samples). Statistical significance and p values are determined by two-sided Student t-test; *** p ≤ 0.001.
a,b, Images for swelling of a bioadhesive microparticle in DMEM (a) and the corresponding time vs. swelling ratio (b). c, Images of the cross-sectional view of blood-covered porcine heart sealed by the barnacle-glue-inspired paste 5 min and 24 h after haemostatic sealing. L0, thickness of the barnacle-glue-inspired paste 5 min after haemostatic sealing. d, Normalized thickness of the crosslinked barnacle-glue-inspired paste between porcine heart over time. L, thickness of the paste at the current time.
a, Rapid haemostatic sealing of an ex vivo porcine aorta by the barnacle-glue-inspired paste. A heparinized porcine blood is used to ensure coagulation-independent haemostatic sealing. b, Images of a filtered porcine blood bath with a 100-µm mesh after 6 h continuous flow through a sealed ex vivo porcine aorta. c, Burst pressure of porcine aorta sealed by the barnacle-glue-inspired paste and commercially available products. d, Haemostatic sealing of a bleeding rat liver in vivo by Surgicel. e, Excised rat liver 2 weeks after haemostatic sealing by Surgicel. f, Haemostatic sealing of a bleeding rat liver in vivo by CoSeal. g, Excised rat liver 2 weeks after haemostatic sealing by CoSeal. Four independent experiments were conducted with similar results. h, Haemostatic sealing of a bleeding rat heart in vivo by Surgicel. i, Haemostatic sealing of a bleeding rat heart in vivo by CoSeal. Four independent experiments were conducted with similar results. Values in c represent the mean and the standard deviation (n = 3; independent samples). Statistical significance and p values are determined by two-sided Student t-test; *** p ≤ 0.001.
Supplementary discussion, references, figures and video captions.
Overall process of adhesion formation between blood-covered tissues by the barnacle-glue-inspired paste.
Repelling of blood by the barnacle-glue-inspired paste applied on a porcine aorta.
Application of commercially available haemostatic agents (TachoSil and Veriset) to a bleeding aorta.
Rapid coagulation-independent haemostatic tissue sealing by the barnacle-glue-inspired paste.
Application of the commercially available haemostatic agents to a bleeding in vivo rat heart.
Rapid haemostatic tissue sealing of a bleeding in vivo rat heart by the barnacle-glue-inspired paste.
Application of a commercially available haemostatic agent (TachoSil) to a bleeding in vivo porcine liver.
Rapid haemostatic tissue sealing of a bleeding in vivo porcine liver by the barnacle-glue-inspired paste.
Rescue of a failed liver haemostasis with TachoSil by the barnacle-glue-inspired paste.
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Yuk, H., Wu, J., Sarrafian, T.L. et al. Rapid and coagulation-independent haemostatic sealing by a paste inspired by barnacle glue. Nat Biomed Eng 5, 1131–1142 (2021). https://doi.org/10.1038/s41551-021-00769-y
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