after tens of thousands of cycles of inflation-deflation (fig. S18 and movie S5). The measured
burst pressures of the TA sealant without and with
a plastic backing were 206 mmHg and 367 mmHg,
respectively (Fig. 4C); these values exceed normal arterial blood pressure in humans (80 to
120 mmHg) and the performance of commercially available surgical sealants (24, 30). Notably,
the TA sealant malfunctioned due to cohesive
failure, which is indicative of a strong adhesion
interface (fig. S18 and movie S6). We also developed
an injectable TA based on an Alg–polyethylene
glycol hydrogel (24). It can be injected via syringe
into a defect site and can form a tough matrix
upon exposure to ultraviolet light (fig. S19). As
a proof of concept, the injectable TA was used
to repair a cylindrical defect in explanted cartilage
discs, resulting in recovery of the compressive
properties (fig. S20).
Tough adhesives can be used as a hemostatic
dressing because of their compatibility with blood
exposure, as shown in a hepatic hemorrhage
model. A circular laceration was used to pro-
duce heavy bleeding on the left lobe of the liver
in rats (24). Animals were treated immediately
with the TA or with a commercial hemostat
[SURGIFLO (Ethicon)] as a positive control or
were left untreated as a negative control (Fig. 4D).
The blood loss was significantly reduced by the
application of the TA versus the negative control,
and the TA’s performance was comparable to
that of SURGIFLO (Fig. 4E). All animals survived
for the experimental period of 2 weeks without
secondary hemorrhage. However, substantial adhe-
sions were found at the lesion site when untreated
or treated with SURGIFLO; necrosis occurred in
the livers of untreated animals (fig. S21). Neither
of these were found in the animals treated with
We report design principles of biocompatible
TAs that combine chemical and physical processes
at the interface and in the bulk of the adhesive to
achieve high adhesion energy on various wet and
dynamic surfaces. The mechanical performance
and compatibility with cells and tissues allow
these materials to meet key requirements for next-
generation tissue adhesives.
REFERENCES AND NOTES
1. S. Duflo, S. L. Thibeault, W. Li, X. Z. Shu, G. D. Prestwich,
Tissue Eng. 12, 2171–2180 (2006).
2. B. Sharma et al., Sci. Transl. Med. 5, 167ra6 (2013).
3. M. R. Prausnitz, R. Langer, Nat. Biotechnol. 26, 1261–1268
4. J. Li, D. J. Mooney, Nat. Rev. Mater. 1, 16071 (2016).
5. C. Ghobril, K. Charoen, E. K. Rodriguez, A. Nazarian,
M. W. Grinstaff, Angew. Chem. Int. Ed. 52, 14070–14074 (2013).
6. M. W. Grinstaff, Biomaterials 28, 5205–5214 (2007).
7. E. T. Roche et al., Adv. Mater. 26, 1200–1206 (2014).
8. R. Feiner et al., Nat. Mater. 15, 679–685 (2016).
9. K. A. Vakalopoulos et al., Ann. Surg. 261, 323– 331 (2015).
10. H. V. Vinters, K. A. Galil, M. J. Lundie, J. C. Kaufmann,
Neuroradiology 27, 279–291 (1985).
11. S. Rose et al., Nature 505, 382–385 (2014).
12. D. G. Barrett, G. G. Bushnell, P. B. Messersmith, Adv. Healthc.
Mater. 2, 745–755 (2013).
13. D. H. Sierra, J. Biomater. Appl. 7, 309– 352 (1993).
14. D. G. Wallace et al., J. Biomed. Mater. Res. 58, 545–555
15. A. K. Dastjerdi, M. Pagano, M. T. Kaartinen, M. D. McKee,
F. Barthelat, Acta Biomater. 8, 3349–3359 (2012).
16. M. Moretti et al., J. Biomech. 38, 1846–1854 (2005).
17. J. M. Pawlicki et al., J. Exp. Biol. 207, 1127–1135 (2004).
18. A. M. Wilks, S. R. Rabice, H. S. Garbacz, C. C. Harro,
A. M. Smith, J. Exp. Biol. 218, 3128–3137 (2015).
19. M. Braun, M. Menges, F. Opoku, A. M. Smith, J. Exp. Biol. 216,
20. J. Y. Sun et al., Nature 489, 133–136 (2012).
21. N. Nakajima, Y. Ikada, Bioconjug. Chem. 6, 123–130
22. M. A. Gilles, A. Q. Hudson, C. L. Borders Jr., Anal. Biochem.
184, 244–248 (1990).
23. J. G. Fernandez et al., Tissue Eng. Part A 23, 135–142
24. Materials and methods are available as supplementary
25. A. N. Gent, Langmuir 12, 4492–4496 (1996).
26. J. W. Hutchinson, Z. Suo, Adv. Appl. Mech. 29, 63–191
27. H. Yuk, T. Zhang, S. Lin, G. A. Parada, X. Zhao, Nat. Mater. 15,
28. T. Stefanov, B. Ryan, A. Ivanković, N. Murphy, Int. J. Adhes.
Adhes. 68, 142–155 (2016).
29. N. Lang et al., Sci. Transl. Med. 6, 218ra6 (2014).
30. P. K. Campbell, S. L. Bennett, A. Driscoll, A. S. Sawhney,
“Evaluation of absorbable surgical sealants: In vitro testing”
(Covidien, 2005); www.covidien.com/imageServer.aspx/
This work was supported by the NIH under award R01DE0130333
and was performed, in part, at the Center for Nanoscale Systems at
Harvard University. A. D.C. acknowledges support from a Marie Curie
International Outgoing Fellowship funded by the European Commission
(agreement 629320). W. W. acknowledges support from Science
Foundation Ireland under grant SFI/12/RC/2278. Q. Y. acknowledges
a scholarship from Tsinghua University. Z.S. and J. J.V. acknowledge
support from the NSF under award CMMI-1404653. Z.S., J.J.V., and D.J.M.
acknowledge support from the Harvard University Materials Research
Science and Engineering Center (grant DMR-1420570). J.L., A.D. C., and
D.J.M. are inventors on U.S. patent applications (US 62/311,646, US
62/356,939, and PC T/US2017/023538) submitted by Harvard
University that cover the design of TAs.
Materials and Methods
Figs. S1 to S21
Movies S1 to S6
25 July 2016; resubmitted 27 April 2017
Accepted 22 June 2017
Fig. 4. Application enabled by TAs. (A) TAs were used as tissue
adhesives. A TA adhered to the liver and sustained 14 times its initial length
(l) before debonding. Scale bars, 20 mm. (B) TAs served as heart
sealants. The TA sealant prevented liquid (red) leakage as the porcine
heart was inflated. DP, change in pressure. Scale bars, 10 mm. (C) Burst
pressures of the TA sealant were measured without (TA) and with plastic
backing (TA-B). (D) Use of a TA as a hemostatic dressing. A deep wound
was created on rat liver and then sealed with a TA to stop the blood
flow (labeled with red arrows). (E) Blood loss with the treatment of TA,
SURGIFLO hemostat, and control (without treatment). Error bars indicate
SD; N = 4. P values were determined by a Student’s t test; ***P ≤ 0.001;
ns, not significant.
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