Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Overcoming the translational barriers of tissue adhesives

Abstract

For the past few decades, tissue sealants and adhesives have been developed as an alternative to sutures and staples to close and seal wounds or incisions. These materials are advantageous because of their ease of use, short application time and minimal tissue damage, making them suitable for minimally invasive procedures. However, there is a large gap between the amount of research into tissue adhesives and the number of products available. To bridge this gap, there is a need to better understand the challenges to clinical translation of tissue adhesives. In particular, adhesive design must be informed by a deep understanding of the target tissue’s surface characteristics and environment, which vary considerably among tissue types. Moreover, understanding and monitoring the long-term performance of a material post-implantation is crucial; this includes monitoring the chemical and physical properties of the implanted adhesives over time, tissue responses and the resultant changes in adhesion and cohesion. In addition, early-stage consideration of the unmet clinical need and the regulatory and development paths could lower the barriers in the development cost and effort, facilitating clinical translation. In this Review, we identify challenges in the development of tissue adhesives and provide design criteria to translate tissue-adhesive technologies into clinical practice.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: A brief history of tissue adhesive research and development.
Fig. 2: Rational material design for clinical applications.
Fig. 3: Potential interactions between tissue adhesives and the surrounding tissues.
Fig. 4: The key steps in the translational process and the regulatory pathways for different classes of tissue adhesives.

Similar content being viewed by others

References

  1. Market Research Engine. Global wound closure products market expected to be worth US $ 15 billion by 2022 (Market Research Engine, 2018).

  2. Artzi, N. Sticking with the pattern for a safer glue. Sci. Transl Med. 5, 205ec161 (2013).

    Google Scholar 

  3. George, W. D. Suturing or stapling in gastrointestinal surgery: a prospective randomized study. Br. J. Surg. 78, 337–341 (1991).

    Google Scholar 

  4. Slieker, J. C., Daams, F., Mulder, I. M., Jeekel, J. & Lange, J. F. Systematic review of the technique of colorectal anastomosis. JAMA Surg. 148, 190–201 (2013).

    Google Scholar 

  5. Edmiston, C. E. et al. Microbiology of explanted suture segments from infected and noninfected surgical patients. J. Clin. Microbiol. 51, 417–421 (2013).

    CAS  Google Scholar 

  6. Owens, C. D. & Stoessel, K. Surgical site infections: epidemiology, microbiology and prevention. J. Hosp. Infect. 70, 3–10 (2008).

    Google Scholar 

  7. Matossian, C., Makari, S. & Potvin, R. Cataract surgery and methods of wound closure: a review. Clin. Ophthalmol. 9, 921–928 (2015).

    Google Scholar 

  8. Masket, S. et al. Hydrogel sealant versus sutures to prevent fluid egress after cataract surgery. J. Cataract Refract. Surg. 40, 2057–2066 (2014).

    Google Scholar 

  9. Lequaglie, C., Giudice, G., Marasco, R., Morte, A. D. & Gallo, M. Use of a sealant to prevent prolonged air leaks after lung resection: a prospective randomized study. J. Cardiothorac. Surg. 7, 106 (2012).

    Google Scholar 

  10. Lang, N. et al. A blood-resistant surgical glue for minimally invasive repair of vessels and heart defects. Sci. Transl Med. 6, 218ra6 (2014).

    Google Scholar 

  11. Sidle, D. M., Loos, B. M., Ramirez, A. L., Kabaker, S. S. & Maas, C. S. Use of BioGlue surgical adhesive for brow fixation in endoscopic browplasty. Arch. Facial Plast. Surg. 7, 393–397 (2005).

    Google Scholar 

  12. Petersen, B. et al. Tissue adhesives and fibrin glues. Gastrointest. Endosc. 60, 327–333 (2004).

    Google Scholar 

  13. Grand View Research. Surgical sealants and adhesives market analysis by type (natural or biological adhesives & sealants, synthetic & semi synthetic adhesives), by application, by region, and segment forecasts, 2018–2025 (Grand View Research, 2017).

  14. Cronkite, E. P., Lozner, E. L. & Deaver, J. M. Use of thrombin and fibrinogen in skin grafting: preliminary report. JAMA 124, 976–978 (1944).

    Google Scholar 

  15. Young, J. Z. & Medawar, P. B. Fibrin suture of peripheral nerves: measurement of the rate of regeneration. Lancet 236, 126–128 (1940).

    Google Scholar 

  16. Spotnitz, W. D. Fibrin sealant: past, present, and future: a brief review. World J. Surg. 34, 632–634 (2010).

    Google Scholar 

  17. Spotnitz, W. D. Fibrin sealant: the only approved hemostat, sealant, and adhesive – a laboratory and clinical perspective. ISRN Surg. 2014, 203943 (2014).

    Google Scholar 

  18. Gundry, S. R., Black, K. & Izutani, H. Sutureless coronary artery bypass with biologic glued anastomoses: preliminary in vivo and in vitro results. J. Thorac. Cardiovasc. Surg. 120, 473–477 (2000).

    CAS  Google Scholar 

  19. Chao, H.-H. & Torchiana, D. F. BioGlue: albumin/glutaraldehyde sealant in cardiac surgery. J. Card. Surg. 18, 500–503 (2003).

    Google Scholar 

  20. Singer, A. J., Perry, L. C. & Allen, R. L. Jr In vivo study of wound bursting strength and compliance of topical skin adhesives. Acad. Emerg. Med. 15, 1290–1294 (2008).

    Google Scholar 

  21. Leggat, P. A., Smith, D. R. & Kedjarune, U. Surgical applications of cyanoacrylate adhesives: a review of toxicity. ANZ J. Surg. 77, 209–213 (2007).

    Google Scholar 

  22. Pascual, G. et al. Cytotoxicity of cyanoacrylate-based tissue adhesives and short-term preclinical in vivo biocompatibility in abdominal hernia repair. PLOS ONE 11, e0157920 (2016).

    Google Scholar 

  23. Dumville, J. C. et al. Tissue adhesives for closure of surgical incisions. Cochrane Database Syst. Rev. 28, CD004287 (2014).

    Google Scholar 

  24. Oliva, N. et al. Personalizing biomaterials for precision nanomedicine considering the local tissue microenvironment. Adv. Healthc. Mater. 4, 1584–1599 (2015).

    CAS  Google Scholar 

  25. Bhagat, V. & Becker, M. L. Degradable adhesives for surgery and tissue engineering. Biomacromolecules 18, 3009–3039 (2017).

    CAS  Google Scholar 

  26. Artzi, N. et al. In vivo and in vitro tracking of erosion in biodegradable materials using non-invasive fluorescence imaging. Nat. Mater. 10, 704–709 (2011).

    CAS  Google Scholar 

  27. Oliva, N. et al. Regulation of dendrimer/dextran material performance by altered tissue microenvironment in inflammation and neoplasia. Sci. Transl Med. 7, 272ra11 (2015).

    Google Scholar 

  28. López-Guerra, D. et al. Postoperative bleeding and biliary leak after liver resection: a cohort study between two different fibrin sealant patches. Sci. Rep. 9, 12001 (2019).

    Google Scholar 

  29. Vakalopoulos, K. et al. Mechanical strength and rheological properties of tissue adhesives with regard to colorectal anastomosis: an ex vivo study. Ann. Surg. 261, 323–331 (2015).

    Google Scholar 

  30. Jue, B. & Maurice, D. M. The mechanical properties of the rabbit and human cornea. J. Biomech. 19, 847–853 (1986).

    CAS  Google Scholar 

  31. Khanafer, K. et al. Determination of the elastic modulus of ascending thoracic aortic aneurysm at different ranges of pressure using uniaxial tensile testing. J. Thorac. Cardiovasc. Surg. 142, 682–686 (2011).

    Google Scholar 

  32. Park, D. Y. et al. The use of microfluidic spinning fiber as an ophthalmology suture showing the good anastomotic strength control. Sci. Rep. 7, 16264 (2017).

    Google Scholar 

  33. Roy, C. K. et al. Self-adjustable adhesion of polyampholyte hydrogels. Adv. Mater. 27, 7344–7348 (2015).

    CAS  Google Scholar 

  34. Li, J. et al. Tough adhesives for diverse wet surfaces. Science 357, 378–381 (2017).

    CAS  Google Scholar 

  35. Liu, B. et al. Hydrogen bonds autonomously powered gelatin methacrylate hydrogels with super-elasticity, self-heal and underwater self-adhesion for sutureless skin and stomach surgery and E-skin. Biomaterials 171, 83–96 (2018).

    CAS  Google Scholar 

  36. Fan, H., Wang, J., Zhang, Q. & Jin, Z. Tannic acid-based multifunctional hydrogels with facile adjustable adhesion and cohesion contributed by polyphenol supramolecular chemistry. ACS Omega 2, 6668–6676 (2017).

    CAS  Google Scholar 

  37. Matsuda, M., Inoue, M. & Taguchi, T. Adhesive properties and biocompatibility of tissue adhesives composed of various hydrophobically modified gelatins and disuccinimidyl tartrate. J. Bioact. Compat. Polym. 27, 481–498 (2012).

    Google Scholar 

  38. Mizuta, R. & Taguchi, T. Enhanced sealing by hydrophobic modification of Alaska pollock-derived gelatin-based surgical sealants for the treatment of pulmonary air leaks. Macromol. Biosci. 17, 1600349 (2017).

    Google Scholar 

  39. Yoshizawa, K. & Taguchi, T. Bonding behavior of hydrophobically modified gelatin films on the intestinal surface. J. Bioact. Compat. Polym. 29, 560–571 (2014).

    CAS  Google Scholar 

  40. Matsuda, M., Inoue, M. & Taguchi, T. Enhanced bonding strength of a novel tissue adhesive consisting of cholesteryl group-modified gelatin and disuccinimidyl tartarate. J. Bioact. Compat. Polym. 27, 31–44 (2012).

    CAS  Google Scholar 

  41. Michel, R. et al. Interfacial fluid transport is a key to hydrogel bioadhesion. Proc. Natl Acad. Sci. USA 116, 738–743 (2019).

    CAS  Google Scholar 

  42. Rogers, A. C., Turley, L. P., Cross, K. S. & McMonagle, M. P. Meta-analysis of the use of surgical sealants for suture-hole bleeding in arterial anastomoses. Br. J. Surg. 103, 1758–1767 (2016).

    CAS  Google Scholar 

  43. Murdock, M. H. et al. Cytocompatibility and mechanical properties of surgical sealants for cardiovascular applications. J. Thorac. Cardiovasc. Surg. 157, 176–183 (2019).

    Google Scholar 

  44. Matthews, P. B. et al. Mechanical properties of surgical glues used in aortic root replacement. Ann. Thorac. Surg. 87, 1154–1160 (2009).

    Google Scholar 

  45. Natour, E., Suedkamp, M. & Dapunt, O. E. Assessment of the effect on blood loss and transfusion requirements when adding a polyethylene glycol sealant to the anastomotic closure of aortic procedures: a case–control analysis of 102 patients undergoing Bentall procedures. J. Cardiothorac. Surg. 7, 105 (2012).

    Google Scholar 

  46. Skorpil, J. et al. Effective and rapid sealing of coronary, aortic and atrial suture lines. Interact. Cardiovasc. Thorac. Surg. 20, 720–724 (2015).

    Google Scholar 

  47. Bhamidipati, C. M., Coselli, J. S. & LeMaire, S. A. BioGlue® in 2011: what is its role in cardiac surgery? J. Extra. Corpor. Technol. 44, P6–P12 (2012).

    Google Scholar 

  48. LeMaire, S. A. et al. Nerve and conduction tissue injury caused by contact with BioGlue. J. Surg. Res. 143, 286–293 (2007).

    CAS  Google Scholar 

  49. LeMaire, S. A. et al. BioGlue surgical adhesive impairs aortic growth and causes anastomotic strictures. Ann. Thorac. Surg. 73, 1500–1506 (2002).

    Google Scholar 

  50. Pasic, M., Unbehaun, A., Drews, T. & Hetzer, R. Late wound healing problems after use of BioGlue® for apical hemostasis during transapical aortic valve implantation. Interact. Cardiovasc. Thorac. Surg. 13, 532–535 (2011).

    Google Scholar 

  51. Fürst, W. & Banerjee, A. Release of glutaraldehyde from an albumin-glutaraldehyde tissue adhesive causes significant in vitro and in vivo toxicity. Ann. Thorac. Surg. 79, 1522–1528 (2005).

    Google Scholar 

  52. Park, J. S. et al. Risk factors of anastomotic leakage and long-term survival after colorectal surgery. Medicine 95, e2890 (2016).

    Google Scholar 

  53. Phillips, B. Reducing gastrointestinal anastomotic leak rates: review of challenges and solutions. Open Access Surg. 9, 5–14 (2016).

    Google Scholar 

  54. Bae, K.-B., Kim, S.-H., Jung, S.-J. & Hong, K.-H. Cyanoacrylate for colonic anastomosis; is it safe? Int. J. Colorectal Dis. 25, 601–606 (2010).

    Google Scholar 

  55. Vuocolo, T. et al. A highly elastic and adhesive gelatin tissue sealant for gastrointestinal surgery and colon anastomosis. J. Gastrointest. Surg. 16, 744–752 (2012).

    Google Scholar 

  56. Li, Y.-W. et al. Very early colorectal anastomotic leakage within 5 post-operative days: a more severe subtype needs relaparatomy. Sci. Rep. 7, 39936 (2017).

    CAS  Google Scholar 

  57. Hyman, N., Manchester, T. L., Osler, T., Burns, B. & Cataldo, P. A. Anastomotic leaks after intestinal anastomosis: it’s later than you think. Ann. Surg. 245, 254–258 (2007).

    Google Scholar 

  58. Silecchia, G. et al. The use of fibrin sealant to prevent major complications following laparoscopic gastric bypass: results of a multicenter, randomized trial. Surg. Endosc. 22, 2492–2497 (2008).

    Google Scholar 

  59. Slieker, J. C., Vakalopoulos, K. A., Komen, N. A., Jeekel, J. & Lange, J. F. Prevention of leakage by sealing colon anastomosis: experimental study in a mouse model. J. Surg. Res. 184, 819–824 (2013).

    Google Scholar 

  60. Trotter, J. et al. The use of a novel adhesive tissue patch as an aid to anastomotic healing. Ann. R. Coll. Surg. Engl. 100, 230–234 (2018).

    CAS  Google Scholar 

  61. Vakalopoulos, K. A. et al. Tissue adhesives in gastrointestinal anastomosis: a systematic review. J. Surg. Res. 180, 290–300 (2013).

    CAS  Google Scholar 

  62. Nordentoft, T., Pommergaard, H. C., Rosenberg, J. & Achiam, M. P. Fibrin glue does not improve healing of gastrointestinal anastomoses: a systematic review. Eur. Surg. Res. 54, 1–13 (2014).

    Google Scholar 

  63. Goulder, F. Bowel anastomoses: the theory, the practice and the evidence base. World J. Gastrointest. Surg. 4, 208–213 (2012).

    Google Scholar 

  64. Urbanavičius, L., Pattyn, P., Van de Putte, D. & Venskutonis, D. How to assess intestinal viability during surgery: a review of techniques. World J. Gastrointest. Surg. 3, 59–69 (2011).

    Google Scholar 

  65. Shogan, B. D. et al. Collagen degradation and MMP9 activation by Enterococcus faecalis contribute to intestinal anastomotic leak. Sci. Transl Med. 7, 286ra68 (2015).

    Google Scholar 

  66. Shogan, B. D. et al. Intestinal anastomotic injury alters spatially defined microbiome composition and function. Microbiome. 2, 35 (2014).

    Google Scholar 

  67. van Praagh, J. B. et al. Intestinal microbiota and anastomotic leakage of stapled colorectal anastomoses: a pilot study. Surg. Endosc. 30, 2259–2265 (2016).

    Google Scholar 

  68. Shakhsheer, B. et al. Morphine promotes colonization of anastomotic tissues with collagenase-producing Enterococcus faecalis and causes leak. J. Gastrointest. Surg. 20, 1744–1751 (2016).

    Google Scholar 

  69. Gaines, S., Shao, C., Hyman, N. & Alverdy, J. C. Gut microbiome influences on anastomotic leak and recurrence rates following colorectal cancer surgery. Br. J. Surg. 105, e131–e141 (2018).

    CAS  Google Scholar 

  70. Pommergaard, H. C., Rosenberg, J., Schumacher-Petersen, C. & Achiam, M. P. Choosing the best animal species to mimic clinical colon anastomotic leakage in humans: a qualitative systematic review. Eur. Surg. Res. 47, 173–181 (2011).

    CAS  Google Scholar 

  71. Nagel, S. J. et al. Spinal dura mater: biophysical characteristics relevant to medical device development. J. Med. Eng. Technol. 42, 128–139 (2018).

    Google Scholar 

  72. Protasoni, M. et al. The collagenic architecture of human dura mater. J. Neurosurg. 114, 1723–1730 (2011).

    Google Scholar 

  73. Hutter, G., von Felten, S., Sailer, M. H., Schulz, M. & Mariani, L. Risk factors for postoperative CSF leakage after elective craniotomy and the efficacy of fleece-bound tissue sealing against dural suturing alone: a randomized controlled trial. J. Neurosurg. 121, 735–744 (2014).

    Google Scholar 

  74. Esposito, F. et al. Fibrin sealants in dura sealing: a systematic literature review. PLOS ONE 12, e0175619 (2016).

    Google Scholar 

  75. Yu, F. et al. Current developments in dural repair: a focused review on new methods and materials. Front. Biosci. 18, 1335–1343 (2013).

    CAS  Google Scholar 

  76. Narotam, P. K., Qiao, F. & Nathoo, N. Collagen matrix duraplasty for posterior fossa surgery: evaluation of surgical technique in 52 adult patients. J. Neurosurg. 111, 380–386 (2009).

    Google Scholar 

  77. Spotnitz, W. D. in Musculoskeletal Tissue Regeneration (ed. Pietrzak, W. S.) 531–546 (Humana, 2008).

  78. Kim, K. D. et al. DuraSeal Exact is a safe adjunctive treatment for durotomy in spine: postapproval study. Global Spine J. 9, 272–278 (2018).

    Google Scholar 

  79. Kinaci, A. et al. Effectiveness of dural sealants in prevention of CSF leakage after craniotomy: a systematic review. World Neurosurg. 118, 368–376 (2018).

    Google Scholar 

  80. Van Doormaal, T. et al. Usefulness of sealants for dural closure: evaluation in an in vitro model. Oper. Neurosurg. 15, 425–432 (2017).

    Google Scholar 

  81. Lee, S.-H., Park, C.-W., Lee, S.-G. & Kim, W.-K. Postoperative cervical cord compression induced by hydrogel dural sealant (DuraSeal®). Korean J. Spine 10, 44–46 (2013).

    Google Scholar 

  82. Smyth, M. D. Hydrogel-induced cervicomedullary compression after posterior fossa decompression for Chiari malformation. J. Neurosurg. Pediatr. 106, 302–304 (2007).

    Google Scholar 

  83. Chenault, H. K. et al. Sealing and healing of clear corneal incisions with an improved dextran aldehyde-PEG amine tissue adhesive. Curr. Eye Res. 36, 997–1004 (2011).

    CAS  Google Scholar 

  84. Park, H. C., Champakalakshmi, R., Panengad, P. P., Raghunath, M. & Mehta, J. S. Tissue adhesives in ocular surgery. Expert. Rev. Ophthalmol. 6, 631–655 (2011).

    Google Scholar 

  85. Baker-Schena, L. Ocular sealants: one new option, but still room for innovation (EyeNet Magazine, 2014).

  86. Refojo, M. F. Current status of biomaterials in ophthalmology. Surv. Ophthalmol. 26, 257–265 (1982).

    CAS  Google Scholar 

  87. Sharma, A. et al. Fibrin glue versus N-butyl-2-cyanoacrylate in corneal perforations. Ophthalmology 110, 291–298 (2003).

    Google Scholar 

  88. Kasetsuwan, N. et al. Efficacy and safety of ethyl-2-cyanoacrylate adhesives for corneal gluing. Asian Biomed. 7, 437–441 (2013).

    CAS  Google Scholar 

  89. Bhatia, S. S. Ocular surface sealants and adhesives. Ocul. Surf. 4, 146–154 (2006).

    Google Scholar 

  90. Guhan, S. et al. Surgical adhesives in ophthalmology: history and current trends. Br. J. Ophthalmol. 102, 1328–1335 (2018).

    Google Scholar 

  91. Nallasamy, N., Grove, K. E., Legault, G. L., Daluvoy, M. B. & Kim, T. Hydrogel ocular sealant for clear corneal incisions in cataract surgery. J. Cataract Refract. Surg. 43, 1010–1014 (2017).

    Google Scholar 

  92. US Food and Drug Administration. ReSure® sealant. Summary of safety and effectiveness data (FDA, 2013).

  93. Wain, J. C. et al. Trial of a novel synthetic sealant in preventing air leaks after lung resection. Ann. Thorac. Surg. 71, 1623–1629 (2001).

    CAS  Google Scholar 

  94. Okereke, I., Murthy, S. C., Alster, J. M., Blackstone, E. H. & Rice, T. W. Characterization and importance of air leak after lobectomy. Ann. Thorac. Surg. 79, 1167–1173 (2005).

    Google Scholar 

  95. Malapert, G., Hanna, H. A., Pages, P. B. & Bernard, A. Surgical sealant for the prevention of prolonged air leak after lung resection: meta-analysis. Ann. Thorac. Surg. 90, 1779–1785 (2010).

    Google Scholar 

  96. Annabi, N. et al. Engineering a highly elastic human protein-based sealant for surgical applications. Sci. Transl Med. 9, eaai7466 (2017).

    Google Scholar 

  97. Fenn, S. L., Charron, P. N. & Oldinski, R. A. Anticancer therapeutic alginate-based tissue sealants for lung repair. ACS Appl. Mater. Interfaces 9, 23409–23419 (2017).

    CAS  Google Scholar 

  98. Santini, M. et al. Use of an electrothermal bipolar tissue sealing system in lung surgery. Eur. J. Cardiothorac. Surg. 29, 226–230 (2006).

    Google Scholar 

  99. US Food and Drug Administration. Premarket approval (PMA) for ProGEL pleural air leak sealant (FDA, 2010).

  100. Belda-Sanchís, J., Serra-Mitjans, M., Iglesias Sentis, M. & Rami, R. Surgical sealant for preventing air leaks after pulmonary resections in patients with lung cancer. Cochrane Database Syst. Rev. 20, CD003051 (2010).

    Google Scholar 

  101. ASTM International. ASTM F2392-04(2015). Standard test method for burst strength of surgical sealants (ASTM, 2015).

  102. ASTM International. ASTM F2458-05(2015), standard test method for wound closure Strength of tissue adhesives and sealants (ASTM, 2015).

  103. Ghobril, C. & Grinstaff, M. W. The chemistry and engineering of polymeric hydrogel adhesives for wound closure: a tutorial. Chem. Soc. Rev. 44, 1820–1835 (2015).

    CAS  Google Scholar 

  104. Annabi, N. et al. Surgical materials: current challenges and nano-enabled solutions. Nano Today 9, 574–589 (2014).

    CAS  Google Scholar 

  105. Annabi, N., Yue, K., Tamayol, A. & Khademhosseini, A. Elastic sealants for surgical applications. Eur. J. Pharm. Biopharm. 95, 27–39 (2015).

    CAS  Google Scholar 

  106. Duarte, A. P., Coelho, J. F., Bordado, J. C., Cidade, M. T. & Gil, M. H. Surgical adhesives: systematic review of the main types and development forecast. Prog. Polym. Sci. 37, 1031–1050 (2012).

    CAS  Google Scholar 

  107. Zhu, W., Chuah, Y. J. & Wang, D.-A. Bioadhesives for internal medical applications: a review. Acta Biomater. 74, 1–16 (2018).

    CAS  Google Scholar 

  108. Nair, L. S. & Laurencin, C. T. Biodegradable polymers as biomaterials. Prog. Polym. Sci. 32, 762–798 (2007).

    CAS  Google Scholar 

  109. Khanlari, S. & Dubé, M. A. Bioadhesives: a review. Macromol. React. Eng. 7, 573–587 (2013).

    CAS  Google Scholar 

  110. Marin, E., Briceño, M. I. & Caballero-George, C. Critical evaluation of biodegradable polymers used in nanodrugs. Int. J. Nanomed. 8, 3071–3091 (2013).

    Google Scholar 

  111. Caliceti, P. & Veronese, F. M. Pharmacokinetic and biodistribution properties of poly(ethylene glycol)–protein conjugates. Adv. Drug Deliv. Rev. 55, 1261–1277 (2003).

    CAS  Google Scholar 

  112. Kean, T. & Thanou, M. Biodegradation, biodistribution and toxicity of chitosan. Adv. Drug Deliv. Rev. 62, 3–11 (2010).

    CAS  Google Scholar 

  113. Yamaoka, T., Tabata, Y. & Ikada, Y. Distribution and tissue uptake of poly(ethylene glycol) with different molecular weights after intravenous administration to mice. J. Pharm. Sci. 83, 601–606 (1994).

    CAS  Google Scholar 

  114. Menovsky, T. et al. Massive swelling of Surgicel® Fibrillar™ hemostat after spinal surgery. case report and a review of the literature. Minim. Invasive Neurosurg. 54, 257–259 (2011).

    CAS  Google Scholar 

  115. Shazly, T. M. et al. Augmentation of postswelling surgical sealant potential of adhesive hydrogels. J. Biomed. Mater. Res. A 95, 1159–1169 (2010).

    Google Scholar 

  116. Buchowski, J., Good, C., Lenke, L. & Bridwell, K. Epidural spinal cord compression with neurologic deficit associated with intrapedicular application of FloSeal during pedicle screw insertion. Spine J. 8, 120S–121S (2008).

    Google Scholar 

  117. Pinkas, O. & Zilberman, M. Novel gelatin–alginate surgical sealants loaded with hemostatic agents. Int. J. Polym. Mater. 66, 378–387 (2017).

    CAS  Google Scholar 

  118. Unterman, S. et al. Hydrogel nanocomposites with independently tunable rheology and mechanics. ACS Nano 11, 2598–2610 (2017).

    CAS  Google Scholar 

  119. Barrett, D. G., Bushnell, G. G. & Messersmith, P. B. Mechanically robust, negative-swelling, mussel-inspired tissue adhesives. Adv. Healthc. Mater. 2, 745–755 (2013).

    CAS  Google Scholar 

  120. Cho, E., Lee, J. S. & Webb, K. Formulation and characterization of poloxamine-based hydrogels as tissue sealants. Acta Biomater. 8, 2223–2232 (2012).

    CAS  Google Scholar 

  121. Zhang, H. et al. On-demand and negative-thermo-swelling tissue adhesive based on highly branched ambivalent PEG–catechol copolymers. J. Mater. Chem. B 3, 6420–6428 (2015).

    CAS  Google Scholar 

  122. Feng, Q. et al. One-pot solvent exchange preparation of non-swellable, thermoplastic, stretchable and adhesive supramolecular hydrogels based on dual synergistic physical crosslinking. npg Asia Mater. 10, e455 (2018).

    Google Scholar 

  123. Li, C., Sajiki, T., Nakayama, Y., Fukui, M. & Matsuda, T. Novel visible-light-induced photocurable tissue adhesive composed of multiply styrene-derivatized gelatin and poly(ethylene glycol) diacrylate. J. Biomed. Mater. Res. B Appl. Biomater. 66B, 439–446 (2003).

    CAS  Google Scholar 

  124. Strong, M. J. et al. A pivotal randomized clinical trial evaluating the safety and effectiveness of a novel hydrogel dural sealant as an adjunct to dural repair. Oper. Neurosurg. 13, 204–212 (2017).

    Google Scholar 

  125. US Food and Drug Administration. Premarket approval (PMA) for adherus autospray dural sealant (FDA, 2015).

  126. Behrens, A. M. et al. Blood-aggregating hydrogel particles for use as a hemostatic agent. Acta Biomater. 10, 701–708 (2014).

    CAS  Google Scholar 

  127. Artzi, N., Shazly, T., Baker, A. B., Bon, A. & Edelman, E. R. Aldehyde-amine chemistry enables modulated biosealants with tissue-specific adhesion. Adv. Mater. 21, 3399–3403 (2009).

    CAS  Google Scholar 

  128. Hoang Thi, T. T., Lee, Y., Park, K. M. & Park, K. D. Enhanced tissue adhesiveness of injectable gelatin-based hydrogels using thiomer. Front. Bioeng. Biotechnol. https://doi.org/10.3389/conf.FBIOE.2016.01.01392 (2016).

  129. Li, S. Hydrolytic degradation characteristics of aliphatic polyesters derived from lactic and glycolic acids. J. Biomed. Mater. Res. 48, 342–353 (1999).

    CAS  Google Scholar 

  130. Piskin, E. Biodegradable polymers as biomaterials. J. Biomater. Sci. Polym. Ed. 6, 775–795 (1994).

    Google Scholar 

  131. Laycock, B. et al. Lifetime prediction of biodegradable polymers. Prog. Polym. Sci. 71, 144–189 (2017).

    CAS  Google Scholar 

  132. Lyu, S. & Untereker, D. Degradability of polymers for implantable biomedical devices. Int. J. Mol. Sci. 10, 4033–4065 (2009).

    CAS  Google Scholar 

  133. Anderson, J. M., Rodrigues, A. & Chang, D. T. Foreign body reaction to biomaterials. Semin. Immunol. 20, 86–100 (2007).

    Google Scholar 

  134. Franz, S., Rammelt, S., Scharnweber, D. & Simon, J. Immune responses to implants – a review of the implications for the design of immunomodulatory biomaterials. Biomaterials 32, 6692–6709 (2011).

    CAS  Google Scholar 

  135. Kopeček, J. & Ulbrich, K. Biodegradation of biomedical polymers. Prog. Polym. Sci. 9, 1–58 (1983).

    Google Scholar 

  136. Li, Y., Rodrigues, J. & Tomas, H. Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applications. Chem. Soc. Rev. 41, 2193–2221 (2012).

    CAS  Google Scholar 

  137. Kong, H. J., Kaigler, D., Kim, K. & Mooney, D. J. Controlling rigidity and degradation of alginate hydrogels via molecular weight distribution. Biomacromolecules 5, 1720–1727 (2004).

    CAS  Google Scholar 

  138. Charriere, G., Bejot, M., Schnitzler, L., Ville, G. & Hartmann, D. J. Reactions to a bovine collagen implant: clinical and immunologic study in 705 patients. J. Am. Acad. Dermatol. 21, 1203–1208 (1989).

    CAS  Google Scholar 

  139. Cooperman, L. & Michaeli, D. The immunogenicity of injectable collagen. I. A 1-year prospective study. J. Am. Acad. Dermatol. 10, 638–646 (1984).

    CAS  Google Scholar 

  140. Pereira, M. J. N. et al. Combined surface micropatterning and reactive chemistry maximizes tissue adhesion with minimal inflammation. Adv. Healthc. Mater. 3, 565–571 (2014).

    CAS  Google Scholar 

  141. Sebesta, M. J. & Bishoff, J. T. Octylcyanoacrylate skin closure in laparoscopy. J. Endourol. 17, 899–903 (2004).

    Google Scholar 

  142. Epstein, N. Dural repair with four spinal sealants: focused review of the manufacturers’ inserts and the current literature. Spine J. 10, 1065–1068 (2010).

    Google Scholar 

  143. Tamariz, E. et al. Delivery of chemotropic proteins and improvement of dopaminergic neuron outgrowth through a thixotropic hybrid nano-gel. J. Mater. Sci. Mater. Med. 22, 2097 (2011).

    CAS  Google Scholar 

  144. Woo, W., Hong, S., Kim, T.-H., Baek, M.-Y. & Song, S.-W. Delayed pulmonary artery rupture after using BioGlue in cardiac surgery. Korean J. Thorac. Cardiovasc. Surg. 50, 474–476 (2017).

    Google Scholar 

  145. Gaffen, A. & Coleman, G. BioGlue surgical adhesive: reported incidents of chronic inflammation and foreign-body reactions. Can. Med. Assoc. J. 175, 1013 (2006).

    Google Scholar 

  146. Ngaage, D. L., Edwards, W. D., Bell, M. R. & Sundt, T. M. A cautionary note regarding long-term sequelae of biologic glue. J. Thorac. Cardiovasc. Surg. 129, 937–938 (2005).

    Google Scholar 

  147. Cuschieri, A. Tissue adhesives in endosurgery. Surg. Innov. 8, 63–68 (2001).

    CAS  Google Scholar 

  148. Lloris-Carsí, J. M., Barrios, C., Prieto-Moure, B., Lloris-Cejalvo, J. M. & Cejalvo-Lapeña, D. The effect of biological sealants and adhesive treatments on matrix metalloproteinase expression during renal injury healing. PLOS ONE 12, e0177665 (2017).

    Google Scholar 

  149. O’Leary, D. P., Wang, J. H., Cotter, T. G. & Redmond, H. P. Less stress, more success? Oncological implications of surgery-induced oxidative stress. Gut 62, 461–470 (2013).

    Google Scholar 

  150. Hillel, A. T. et al. Photoactivated composite biomaterial for soft tissue restoration in rodents and in humans. Sci. Transl Med. 3, 93ra67 (2011).

    CAS  Google Scholar 

  151. Reid, B. et al. PEG hydrogel degradation and the role of the surrounding tissue environment. J. Tissue Eng. Regen. Med. 9, 315–318 (2015).

    CAS  Google Scholar 

  152. Mouthuy, P.-A. et al. Biocompatibility of implantable materials: an oxidative stress viewpoint. Biomaterials 109, 55–68 (2016).

    CAS  Google Scholar 

  153. Tamariz, E. & Rios-Ramírez, A. in Biodegradation-Life of Science (eds Chamy, R. & Rosenkranz, F.) (IntechOpen, 2013).

  154. Conde, J., Oliva, N. & Artzi, N. Revisiting the ‘one material fits all’ rule for cancer nanotherapy. Trends Biotechnol. 34, 618–626 (2016).

    CAS  Google Scholar 

  155. Gül, N. et al. Surgery-induced reactive oxygen species enhance colon carcinoma cell binding by disrupting the liver endothelial cell lining. Gut 60, 1076–1086 (2011).

    Google Scholar 

  156. Duan, J. & Kasper, D. L. Oxidative depolymerization of polysaccharides by reactive oxygen/nitrogen species. Glycobiology 21, 401–409 (2011).

    CAS  Google Scholar 

  157. Xu, X., Jha, A. K., Harrington, D. A., Farach-Carson, M. C. & Jia, X. Hyaluronic acid-based hydrogels: from a natural polysaccharide to complex networks. Soft Matter 8, 3280–3294 (2012).

    CAS  Google Scholar 

  158. Xu, Q., He, C., Xiao, C. & Chen, X. Reactive oxygen species (ROS) responsive polymers for biomedical applications. Macromol. Biosci. 16, 635–646 (2016).

    CAS  Google Scholar 

  159. Soller, B. R. et al. Feasibility of non-invasive measurement of tissue pH using near-infrared reflectance spectroscopy. J. Clin. Monit. 12, 387–395 (1996).

    CAS  Google Scholar 

  160. Anderson, M., Moshnikova, A., Engelman, D. M., Reshetnyak, Y. K. & Andreev, O. A. Probe for the measurement of cell surface pH in vivo and ex vivo. Proc. Natl Acad. Sci. USA 113, 8177–8181 (2016).

    CAS  Google Scholar 

  161. Barar, J. & Omidi, Y. Dysregulated pH in tumor microenvironment checkmates cancer therapy. BioImpacts 3, 149–162 (2013).

    Google Scholar 

  162. Feng, L., Dong, Z., Tao, D., Zhang, Y. & Liu, Z. The acidic tumor microenvironment: a target for smart cancer nano-theranostics. Natl. Sci. Rev. 5, 269–286 (2018).

    CAS  Google Scholar 

  163. Lin, M.-H. et al. Monitoring the long-term degradation behavior of biomimetic bioadhesive using wireless magnetoelastic sensor. IEEE Trans. Biomed. Eng. 62, 1838–1842 (2015).

    Google Scholar 

  164. Cencer, M. et al. Effect of pH on the rate of curing and bioadhesive properties of dopamine functionalized poly(ethylene glycol) hydrogels. Biomacromolecules 15, 2861–2869 (2014).

    CAS  Google Scholar 

  165. Hong, S. et al. Hyaluronic acid catechol: a biopolymer exhibiting a pH-dependent adhesive or cohesive property for human neural stem cell engineering. Adv. Funct. Mater. 23, 1774–1780 (2013).

    CAS  Google Scholar 

  166. Kohane, D. S. & Langer, R. Biocompatibility and drug delivery systems. Chem. Sci. 1, 441–446 (2010).

    CAS  Google Scholar 

  167. Lei, K. et al. Non-invasive monitoring of in vivo degradation of a radiopaque thermoreversible hydrogel and its efficacy in preventing post-operative adhesions. Acta Biomater. 55, 396–409 (2017).

    CAS  Google Scholar 

  168. Prestwich, G. D. et al. What is the greatest regulatory challenge in the translation of biomaterials to the clinic? Sci. Transl Med. 4, 160cm14 (2012).

    Google Scholar 

  169. Krarup, P.-M., Nordholm-Carstensen, A., Jorgensen, L. N. & Harling, H. Anastomotic leak increases distant recurrence and long-term mortality after curative resection for colonic cancer: a nationwide cohort study. Ann. Surg. 259, 930–938 (2014).

    Google Scholar 

  170. Shao, H. & Stewart, R. J. Biomimetic underwater adhesives with environmentally triggered setting mechanisms. Adv. Mater. 22, 729–733 (2010).

    CAS  Google Scholar 

  171. Roche, E. T. et al. A light-reflecting balloon catheter for atraumatic tissue defect repair. Sci. Transl Med. 7, 306ra149 (2015).

    Google Scholar 

  172. Stam, M. A. W. et al. Sylys® surgical sealant: a safe adjunct to standard bowel anastomosis closure. Ann. Surg. Innov. Res. 8, 6 (2014).

    Google Scholar 

  173. Anseth, K. S. & Burdick, J. A. New directions in photopolymerizable biomaterials. MRS Bull. 27, 130–136 (2002).

    CAS  Google Scholar 

  174. Sabnis, A., Rahimi, M., Chapman, C. & Nguyen, K. T. Cytocompatibility studies of an in situ photopolymerized thermoresponsive hydrogel nanoparticle system using human aortic smooth muscle cells. J. Biomed. Mater. Res. A 91, 52–59 (2009).

    Google Scholar 

  175. Williams, C. G., Malik, A. N., Kim, T. K., Manson, P. N. & Elisseeff, J. H. Variable cytocompatibility of six cell lines with photoinitiators used for polymerizing hydrogels and cell encapsulation. Biomaterials 26, 1211–1218 (2005).

    CAS  Google Scholar 

  176. Pellenc, Q. et al. Preclinical and clinical evaluation of a novel synthetic bioresorbable, on-demand, light-activated sealant in vascular reconstruction. J. Cardiovasc. Surg. 60, 599–611 (2019).

    Google Scholar 

  177. Elvin, C. M. et al. The development of photochemically crosslinked native fibrinogen as a rapidly formed and mechanically strong surgical tissue sealant. Biomaterials 30, 2059–2065 (2009).

    CAS  Google Scholar 

  178. Fu, A., Gwon, K., Kim, M., Tae, G. & Kornfield, J. A. Visible-light-initiated thiol-acrylate photopolymerization of heparin-based hydrogels. Biomacromolecules 16, 497–506 (2015).

    CAS  Google Scholar 

  179. Tan, H. & Marra, K. G. Injectable, biodegradable hydrogels for tissue engineering applications. Materials 3, 1746–1767 (2010).

    CAS  Google Scholar 

  180. Li, L. et al. Biodegradable and injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for postoperative adhesion prevention. Biomaterials 35, 3903–3917 (2014).

    CAS  Google Scholar 

  181. Mo, X., Iwata, H., Matsuda, S. & Ikada, Y. Soft tissue adhesive composed of modified gelatin and polysaccharides. J. Biomater. Sci. Polym. Ed. 11, 341–351 (2000).

    CAS  Google Scholar 

  182. Tan, H., Chu, C. R., Payne, K. A. & Marra, K. G. Injectable in situ forming biodegradable chitosan–hyaluronic acid based hydrogels for cartilage tissue engineering. Biomaterials 30, 2499–2506 (2009).

    CAS  Google Scholar 

  183. Nair, D. P. et al. The thiol-Michael addition click reaction: a powerful and widely used tool in materials chemistry. Chem. Mater. 26, 724–744 (2014).

    CAS  Google Scholar 

  184. Lee, Y. et al. Thermo-sensitive, injectable, and tissue adhesive sol–gel transition hyaluronic acid/pluronic composite hydrogels prepared from bio-inspired catechol-thiol reaction. Soft Matter 6, 977–983 (2010).

    CAS  Google Scholar 

  185. Metters, A. & Hubbell, J. Network formation and degradation behavior of hydrogels formed by Michael-type addition reactions. Biomacromolecules 6, 290–301 (2005).

    CAS  Google Scholar 

  186. Nie, W., Yuan, X., Zhao, J., Zhou, Y. & Bao, H. Rapidly in situ forming chitosan/ε-polylysine hydrogels for adhesive sealants and hemostatic materials. Carbohydr. Polym. 96, 342–348 (2013).

    CAS  Google Scholar 

  187. Lamph, S. Regulation of medical devices outside the European Union. J. R. Soc. Med. 105, 12–21 (2012).

    Google Scholar 

  188. Mahdavi, A. et al. A biodegradable and biocompatible gecko-inspired tissue adhesive. Proc. Natl Acad. Sci. USA 105, 2307–2312 (2008).

    CAS  Google Scholar 

  189. Coover, H. W. Chemistry and performance of cyanoacrylate adhesives. J. Soc. Plast. Eng. 15, 413–417 (1959).

    Google Scholar 

  190. Tatooles, C. J. & Braunwald, N. S. The use of crosslinked gelatin as a tissue adhesive to control hemorrhage from liver and kidney. Surgery 60, 857–861 (1966).

    CAS  Google Scholar 

  191. Mintz, P. D. et al. Fibrin sealant: clinical use and the development of the University of Virginia Tissue Adhesive Center. Ann. Clin. Lab. Sci. 31, 108–118 (2001).

    CAS  Google Scholar 

  192. Ennker, J. et al. The impact of gelatin-resorcinol glue on aortic tissue: a histomorphologic evaluation. J. Vasc. Surg. 20, 34–43 (1994).

    CAS  Google Scholar 

  193. Kowanko, N. Adhesive composition and method. US Patent US5385606A (1993).

  194. Sawhney, A. S., Pathak, C. P. & Hubbell, J. A. Bioerodible hydrogels based on photopolymerized poly(ethylene glycol)-co-poly(α-hydroxy acid) diacrylate macromers. Macromolecules 26, 581–587 (1993).

    CAS  Google Scholar 

  195. FDA. Premarket Approval (PMA) for Dermabond® https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=p960052 (1998).

  196. Barrows, T. H., Lewis, T. W. & Truong, M. T. Adhesive sealant composition. US Patent US5583114A (1994).

  197. Holowka, E. P. & Bhatia, S. K. Drug Delivery: Materials Design and Clinical Perspective (Springer, 2014).

  198. US Food and Drug Administration. Premarket approval (PMA) for BioGlue® (FDA, 2001).

  199. Zhang, J.-Y., Doll, B. A., Beckman, E. J. & Hollinger, J. O. Three-dimensional biocompatible ascorbic acid-containing scaffold for bone tissue engineering. Tissue Eng. 9, 1143–1157 (2003).

    CAS  Google Scholar 

  200. McDermott, M. K., Chen, T., Williams, C. M., Markley, K. M. & Payne, G. F. Mechanical properties of biomimetic tissue adhesive based on the microbial transglutaminase-catalyzed crosslinking of gelatin. Biomacromolecules 5, 1270–1279 (2004).

    CAS  Google Scholar 

  201. Bitton, R. & Bianco-Peled, H. Novel biomimetic adhesives based on algae glue. Macromol. Biosci. 8, 393–400 (2008).

    CAS  Google Scholar 

  202. US Food and Drug Administration. Premarket approval (PMA) for DuraSeal dural sealant system (FDA, 2005).

  203. US Food and Drug Administration. Premarket approval (PMA) for Ethicon OMNEX surgical sealant (FDA, 2010).

  204. US Food and Drug Administration. Premarket approval (PMA) for Cohera Medical TissuGlu (2015).

  205. Jito, J., Nitta, N. & Nozaki, K. Delayed cerebrospinal fluid leak after watertight dural closure with a polyethylene glycol hydrogel dural sealant in posterior fossa surgery: case report. Neurol. Med. Chir. 54, 634–639 (2014).

    Google Scholar 

  206. Sani, E. S. et al. Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels. Sci. Adv. 5, eaav1281 (2019).

    CAS  Google Scholar 

  207. Wuyts, F. L. et al. Elastic properties of human aortas in relation to age and atherosclerosis: a structural model. Phys. Med. Biol. 40, 1577–1597 (1995).

    CAS  Google Scholar 

  208. Annabi, N. et al. Engineering a sprayable and elastic hydrogel adhesive with antimicrobial properties for wound healing. Biomaterials 139, 229–243 (2017).

    CAS  Google Scholar 

  209. Helander, H. F. & Fändriks, L. Surface area of the digestive tract – revisited. Scand. J. Gastroenterol. 49, 681–689 (2014).

    Google Scholar 

  210. Lee, S., Pham, A. M., Pryor, S. G., Tollefson, T. & Sykes, J. M. Efficacy of Crosseal fibrin sealant (human) in rhytidectomy. Arch. Facial Plast. Surg. 11, 29–33 (2009).

    CAS  Google Scholar 

  211. Azuma, K. et al. Biological adhesive based on carboxymethyl chitin derivatives and chitin nanofibers. Biomaterials 42, 20–29 (2015).

    CAS  Google Scholar 

  212. Walgenbach, K. J., Bannasch, H., Kalthoff, S. & Rubin, J. P. Randomized, prospective study of TissuGlu® surgical adhesive in the management of wound drainage following abdominoplasty. Aesthetic Plast. Surg. 36, 491–496 (2012).

    Google Scholar 

  213. Kawai, H. et al. Usefulness of a new gelatin glue sealant system for dural closure in a rat durotomy model. Neurol. Med. Chir. 54, 640–646 (2014).

    Google Scholar 

  214. Lin, K. L. et al. DuraSeal as a ligature in the anastomosis of rat sciatic nerve gap injury. J. Surg. Res. 161, 101–110 (2010).

    CAS  Google Scholar 

  215. Assmann, A. et al. A highly adhesive and naturally derived sealant. Biomaterials 140, 115–127 (2017).

    CAS  Google Scholar 

  216. Florek, H.-J. et al. Results from a first-in-human trial of a novel vascular sealant. Front. Surg. 2, 29 (2015).

    Google Scholar 

  217. Coselli, J. S. et al. Prospective randomized study of a protein-based tissue adhesive used as a hemostatic and structural adjunct in cardiac and vascular anastomotic repair procedures. J. Am. Coll. Surg. 197, 243–252 (2003).

    Google Scholar 

  218. Kopelman, Y. et al. A gelatin-based prophylactic sealant for bowel wall closure, initial evaluation in mid-rectal anastomosis in a large animal model. J. Gastrointest. Dig. Syst. 5, 1–6 (2015).

    Google Scholar 

  219. Tjandra, J. J. & Chan, M. K. Y. A sprayable hydrogel adhesion barrier facilitates closure of defunctioning loop ileostomy: a randomized trial. Dis. Colon Rectum 51, 956–960 (2008).

    Google Scholar 

  220. Muto, G., D’Urso, L., Castelli, E., Formiconi, A. & Bardari, F. Cyanoacrylic glue: a minimally invasive nonsurgical first line approach for the treatment of some urinary fistulas. J. Urol. 174, 2239–2243 (2005).

    CAS  Google Scholar 

  221. Sanders, L., Stone, R., Webb, K., Mefford, T. & Nagatomi, J. Mechanical characterization of a bifunctional Tetronic hydrogel adhesive for soft tissues. J. Biomed. Mater. Res. A 103, 861–868 (2015).

    Google Scholar 

Download references

Acknowledgements

This work was supported by the Korea Institute for Advancement of Technology (N0002123) to Y.L., the MIT Deshpande Center and BioDevek to N.A. and the National Institutes of Health through the R01 grant HL095722 to J.M.K.

Author information

Authors and Affiliations

Authors

Contributions

All authors researched data and contributed to the discussion, writing and revising of the content.

Corresponding authors

Correspondence to Jeffrey M. Karp, Natalie Artzi or Yuhan Lee.

Ethics declarations

Competing interests

G.M.T. is employed by BioDevek, a company that has filed patents based on materials described in this manuscript. G.M.T benefits from the stock options compensation plan from BioDevek. M.J.N.P. is an employee and holds stock options in TISSIUM, a company that further licensed intellectual property (IP) generated by M.J.N.P. and that may benefit financially if the IP is further validated. M.J.N.P. has filed patents based on materials described in this manuscript. J.M.K. holds equity in TISSIUM, a company that has an option to license IP generated by J.M.K. and that may benefit financially if the IP is licensed and further validated. The interests of J.M.K. were reviewed and are subject to a management plan overseen by their institutions in accordance with their conflict of interest policies. J.M.K. has filed patents based on materials described in this manuscript. N.A. holds equity in BioDevek, a company that has an option to license IP generated by N.A. and that may benefit financially if the IP is licensed and further validated. The interests of N.A. were reviewed and are subject to a management plan overseen by their institutions in accordance with their conflict of interest policies. N.A. has filed patents based on materials described in this manuscript. Y.L. has filed patents based on materials described in this manuscript. The other authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Taboada, G.M., Yang, K., Pereira, M.J.N. et al. Overcoming the translational barriers of tissue adhesives. Nat Rev Mater 5, 310–329 (2020). https://doi.org/10.1038/s41578-019-0171-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41578-019-0171-7

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing