Two dry surfaces can instantly adhere upon contact with each other through intermolecular forces such as hydrogen bonds, electrostatic interactions and van der Waals interactions1,2. However, such instant adhesion is challenging when wet surfaces such as body tissues are involved, because water separates the molecules of the two surfaces, preventing interactions3,4. Although tissue adhesives have potential advantages over suturing or stapling5,6, existing liquid or hydrogel tissue adhesives suffer from several limitations: weak bonding, low biological compatibility, poor mechanical match with tissues, and slow adhesion formation5,6,7,8,9,10,11,12,13. Here we propose an alternative tissue adhesive in the form of a dry double-sided tape (DST) made from a combination of a biopolymer (gelatin or chitosan) and crosslinked poly(acrylic acid) grafted with N-hydrosuccinimide ester. The adhesion mechanism of this DST relies on the removal of interfacial water from the tissue surface, resulting in fast temporary crosslinking to the surface. Subsequent covalent crosslinking with amine groups on the tissue surface further improves the adhesion stability and strength of the DST. In vitro mouse, in vivo rat and ex vivo porcine models show that the DST can achieve strong adhesion between diverse wet dynamic tissues and engineering solids within five seconds. The DST may be useful as a tissue adhesive and sealant, and in adhering wearable and implantable devices to wet tissues.
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We thank J. Hu and M. Guo in the Massachusetts Institute of Technology (MIT) Mechanical Engineering Department for their help with the cell viability test; T. McClure in the MIT Materials Research Laboratory for help with the FTIR measurement; and S. Ngoy in the Brigham and Women’s Hospital (BHW) Rodent Cardiovascular Physiology Core for technical support with rodent surgery. This work is supported by the US National Science Foundation (NSF; grant CMMI-1661627) and Office of Naval Research (N00014-17-1-2920). H.Y. acknowledges financial support from a Samsung Scholarship. C.E.V. acknowledges financial support from the NSF Graduate Research Fellowship Program.
H.Y. and X.Z. are inventors of a patent application (US patent 62/845,976) that covers the dry-crosslinking mechanism and the design of DST.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Extended data figures and tables
The DST can be applied directly onto wet tissue surfaces after removing the backing, without any other preparation process. Upon contact with the wet surfaces, the DST dries them by quickly swelling and absorbing the interfacial water. Simultaneously, the carboxylic acid groups in the DST form temporary crosslinks through intermolecular bonds with the tissue surfaces, followed by covalent crosslinking between NHS ester groups in the DST and primary amine groups on the tissues. After adhering on tissues, the swollen DST becomes a thin layer of tough hydrogel which provides robust adhesion between the surfaces. Dissipation indicates the mechanical energy dissipation from the DST during deformation by the applied force, F.
a, Transmission FTIR spectrum of the DST with NHS ester. The carboxylic acid C=O stretch at 1,710 cm−1 is associated with PAAc in the DST. The symmetric C–N–C stretch at 1,219 cm−1 and asymmetric C–N–C stretch at 1,307 cm−1 are associated with NHS ester in the DST35,36. b, Schematic illustration of covalent crosslinking between amine-coupled fluorescent microbeads (µ-beads) with the DST. c, Fluorescence microscopy images of covalently crosslinked microbeads with DST with NHS ester (left) and DST without NHS ester (right).
a, Swelling ratio and thickness of the chitosan-based DST as a function of time after pressing between two wet porcine skins. b, Dark-field microscopic image and bright-field image overlaid with green fluorescence of porcine skins adhered by the chitosan-based DST 5 min after application. c, Dark-field microscopic image and bright-field image overlaid with green fluorescence of porcine skins adhered by the chitosan-based DST 24 h after application. The sample was kept in a wet environment throughout the measurement.
a, The DST is initially prepared as a thin dry film that can conform to tissue surfaces. b, Nominal stress versus engineering strain for the dry DST. The measured Young’s modulus of the dry DST is 5.7 GPa.
a, Standard calibration curve of acrylic acid for HPLC. b, Results of HPLC characterization of the DST extraction solution. The DST has a very low concentration of residual acrylic acid monomers: 74 ng per 1 mg of the DST.
a, Setup for measurement of interfacial toughness, based on the standard 180-degree peel test (ASTM F2256). b, Setup for measurement of shear strength, based on the standard lap-shear test (ASTM F2255). c, Setup for measurement of tensile strength, based on the standard tensile test (ASTM F2258). F, force; Fplateau, plateau force in peel test; Fmax, maximum force in lap-shear and tensile test; L, length; W, width.
Extended Data Fig. 7 Effect of covalent crosslinks on the long-term stability of adhesion by the DST.
a, Interfacial toughness and shear and tensile strength versus pressing time for wet porcine skins adhered by the DST without NHS ester. Note that these adhesion tests were performed immediately after the initial pressing. b, Interfacial toughness and shear and tensile strength versus time after pressing for wet porcine skins adhered by the DST without NHS ester. Note that all samples for b were kept in wet environments before the mechanical tests. Values represent the mean and the standard deviation (n = 3–5).
Shown are typical values for interfacial toughness, shear and tensile strength, and application time required for adhesion formation, for the DST (adhered between hydrogel and porcine skin) and various existing tissue adhesives. The interfacial toughness, shear strength and tensile strength for all commercially available adhesives were measured according to the application manual provided for each product. The application time for commercially available adhesives was based on the application manuals provided. The data for ultraviolet-curable surgical glue24, nanoparticle solution8 and tough hydrogel adhesive12 were obtained from the literature. Values represent the mean and the standard deviation (n = 3–5).
a, Primary amine functionalization of silicon, titanium and PDMS, and subsequent covalent coupling between the primary amine groups and the NHS ester groups in the DST. b, Primary amine functionalization of polycarbonate, and subsequent covalent coupling between the primary amine groups and the NHS ester groups in the DST. c, Primary amine functionalization of polyimide, and subsequent covalent coupling between the primary amine groups and the NHS ester groups in the DST.
a, Sealing of an air-leaking, lacerated ex vivo porcine trachea by a hydrogel patch adhered by the DST. b, Anastomosis of a dissected ex vivo porcine small intestine by the DST.
This file contains Supplementary Texts, Supplementary Figs. 1 to 16, and Supplementary References.
Overall process of adhesion formation between wet porcine skins by the DST.
Adhesion formation between various wet porcine tissues by the DST.
Adhesion formation between wet porcine skins and engineering solids by the DST.
Adhesion of DST-TPU patch on beating rat heart in vivo.
Sealing of an air-leaking ex vivo porcine lung by adhesion of a hydrogel patch by the DST.
Sealing of a fluid-leaking ex vivo stomach by adhesion of a hydrogel patch by the DST.
Anastomosis of a dissected ex vivo small intestine by the DST.
Adhesion of a drug patch on a beating ex vivo porcine heart by the DST.
Adhesion of a strain sensor on a beating ex vivo porcine heart by the DST.
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Yuk, H., Varela, C.E., Nabzdyk, C.S. et al. Dry double-sided tape for adhesion of wet tissues and devices. Nature 575, 169–174 (2019). https://doi.org/10.1038/s41586-019-1710-5
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