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This work is part of and supported by the Deutsche
Forschungsgemeinschaft Collaborative Research Centre “SFB 1225
(ISOQUANT).” Also part of and supported by European Research
Council consolidator grant X-MuSiC-616783 and Helmholtz
Association project-oriented funds. The authors declare no competing
Figs. S1 to S7
31 March 2017; accepted 26 June 2017
Tough adhesives for diverse
J. Li,1,2,3 A. D. Celiz,2,4 J. Yang,1,5 Q. Yang,1,5,6 I. Wamala,7 W. Whyte,1,2,8
B. R. Seo,1,2 N. V. Vasilyev,7 J. J. Vlassak,1 Z. Suo,1,5 D. J. Mooney1,2†
Adhesion to wet and dynamic surfaces, including biological tissues, is important in
many fields but has proven to be extremely challenging. Existing adhesives are cytotoxic,
adhere weakly to tissues, or cannot be used in wet environments. We report a bioinspired
design for adhesives consisting of two layers: an adhesive surface and a dissipative matrix.
The former adheres to the substrate by electrostatic interactions, covalent bonds, and
physical interpenetration. The latter amplifies energy dissipation through hysteresis. The
two layers synergistically lead to higher adhesion energies on wet surfaces as compared
with those of existing adhesives. Adhesion occurs within minutes, independent of blood
exposure and compatible with in vivo dynamic movements. This family of adhesives may be
useful in many areas of application, including tissue adhesives, wound dressings, and
Adhesives that can bond strongly to biolog- ical tissues would have broad applications ranging from tissue repair (1, 2) and drug delivery (3, 4) to wound dressings (5, 6) and biomedical devices (7, 8). However,
existing tissue adhesives are far from ideal. Cya-
noacrylate (Super Glue) is the strongest class
of tissue adhesive (9) but is cytotoxic; is incom-
patible with wet surfaces, as it solidifies imme-
diately upon exposure to water; and forms rigid
plastics that cannot accommodate dynamic move-
ments of tissues (10). Nanoparticle (11) and mussel-
inspired adhesives (12) adhere weakly to tissues,
(13) and polyethylene glycol–based adhesives (14)
like COSEAL (Baxter) and DURASEAL (Confluent
Surgical), can form covalent bonds with tissues.
However, their matrix toughness and adhesion
energies are on the order of 10 J m−2 (15). Such
brittle adhesives are vulnerable to debonding
because of cohesive failure in the adhesive matrix.
For comparison, cartilage constitutes a matrix
of high toughness (1000 J m−2) and bonds to bones
with an adhesion energy of 800 J m−2 (16).
Achieving high adhesion energy requires the
synergy of two effects. First, the adhesive should
form strong bonds with the substrate. Second,
materials inside either the adhesive or the
substrate (or both) should dissipate energy by
hysteresis. Tissue adhesives must also show com-
patibility with body fluids, as well as with cells
and tissues. Here we report the design of a fam-
ily of tough adhesives (TAs) for biological appli-
cations to meet those requirements. The design
is inspired by a defensive mucus secreted by
slugs (Arion subfuscus) that strongly adheres to
wet surfaces (17). This slug adhesive consists of a
tough matrix with interpenetrating positively
charged proteins (18). Our TAs are made up of
two layers: (i) an adhesive surface containing
an interpenetrating positively charged polymer
and (ii) a dissipative matrix (Fig. 1A). The adhesive
surface can bond to the substrate through elec-
trostatic interactions, covalent bonds, and phys-
ical interpenetration, whereas the matrix dissipates
energy through hysteresis under deformation.
The TAs were designed on the basis of two
criteria: (i) The adhesive surface must wet nega-
tively charged surfaces of tissues and cells and
must form covalent bonds across the interface
while being compliant to the dynamic move-
ments of tissues. (ii) The dissipative matrix must
be tough and capable of dissipating energy effec-
tively when the interface is stressed. To satisfy
the first criterion, we employed a bridging poly-
mer that bears positively charged primary amine
groups under physiological conditions. The pri-
mary amine found in the slug adhesive is believed
to play a major role in its mechanics and adhe-
sion (19). Such a polymer can be absorbed to the
tissue surface via electrostatic attractions, enabling
primary amine groups to bind covalently with
carboxylic acid groups from the hydrogel matrix
and the tissue surface (Fig. 1A). If the target sur-
face is permeable, the bridging polymer can also
penetrate into the target surface, forming physical
entanglements, and chemically anchor the adhe-
sive. The second criterion is satisfied by using a
hydrogel capable of dissipating energy as the dissi-
pative matrix. For instance, alginate-polyacrylamide
(Alg-PAAm) hydrogels effectively dissipate energy
under deformation (20). We hypothesize that by
combining the interfacial bridging and the back-
ground hysteresis, the TAs could form strong ad-
hesion on wet surfaces.
With the use of these design principles, we
fabricated a family of TAs that can adhere to wet
surfaces. We chose porcine skin as the first model tissue, as it closely resembles human skin and
is robust, ensuring that ultimate adhesive failure
occurs at the interface. To identify an appropriate
bridging polymer, we tested five polymers: chitosan, polyallylamine (PAA), polyethylenimine, collagen, and gelatin. The bridging polymer penetrated
rapidly into the hydrogel matrix (fig. S1), forming
a positively charged surface (fig. S2). Two coupling
diimide and N-hydroxysulfosuccinimide, were applied to facilitate covalent bond formation (21, 22).
378 28 JULY 2017 • VOL 357 ISSUE 6349 sciencemag.org SCIENCE
1John A. Paulson School of Engineering and Applied
Sciences, Harvard University, Cambridge, MA 02138, USA.
2Wyss Institute for Biologically Inspired Engineering, Harvard
University, Cambridge, MA 02138, USA. 3Department of
Mechanical Engineering, McGill University, Montreal, Quebec
H3A 0G4, Canada. 4Advanced Materials and Healthcare
Technologies Division, School of Pharmacy, University of
Nottingham, Nottingham NG7 2RD, UK. 5Kavli Institute for
Nanobio Science and Technology, Harvard University,
Cambridge, MA 02138, USA. 6School of Aerospace, Tsinghua
University, Beijing 100084, People’s Republic of China.
7Departments of Cardiac Surgery, Boston Children’s Hospital,
Boston, MA 02115, USA. 8Advanced Materials and
Bioengineering Research Centre, Royal College of Surgeons
in Ireland and Trinity College Dublin, Dublin, Ireland.
*These authors contributed equally to this work.
†Corresponding author. Email: firstname.lastname@example.org