A double crosslinking adhesion mechanism for developing tough hydrogel adhesives

Joonsu Han, Jihoon Park, Rimsha Bhatta, Yusheng Liu, Yang Bo, Jingyi Zhou, Hua Wang

Research output: Contribution to journalArticlepeer-review


Tough hydrogel adhesives that consist of a robust gel network and can strongly adhere to wet tissues have shown great promise as the next generation of bioadhesives. While a variety of chemistries can be utilized to construct the tough gel network, the covalent conjugation methods for tissue adhesion are still limited. Here we report, for the first time, the use of side product-free amine-thiolactone chemistry which initiates a double crosslinking adhesion mechanism to develop tough gel adhesives. Thiolactone groups can conjugate with tissue-surface amines via a ring-opening reaction. The resultant thiol end groups can be further crosslinked into disulfide linkages, enabling the formation of a robust and stable adhesion layer. The thiolactone-bearing tough hydrogel composed of methacrylate-modified gelatin, acrylic acid, and thiolacone acrylamide exhibited good biocompatibility and mechanical properties, and strong adhesion to various types of engineering solids and tissues. We also demonstrated its ability to function as a tissue sealant and drug depot. The novel adhesion mechanism will diversify future design of bioadhesives for hemostasis, drug delivery, tissue repair, and other applications. Statement of significance: Tough hydrogel adhesives with excellent tissue-adhesive and mechanical properties have demonstrated tremendous promise for hemostasis, tissue repair, and drug delivery applications. However, the covalent chemistry for tissue adhesion has been limited, which narrows the choice of materials for the design of bioadhesives and may pose a safety concern. Here, for the first time, we report the use of side product-free amine-thiolactone chemistry, which involves a double crosslinking adhesion mechanism, for developing tough hydrogel adhesives. We demonstrate that thiolactone-bearing tough hydrogels exhibit favorable biocompatibility and mechanical properties, and superior adhesion to both engineering solids and tissues. Our new adhesion technology will greatly facilitate future development of advanced bioadhesives for numerous biomedical applications.

Original languageEnglish (US)
Pages (from-to)199-210
Number of pages12
JournalActa Biomaterialia
StatePublished - Sep 15 2022


  • Bioadhesive
  • Drug depot
  • Hydrogel
  • Tissue adhesive
  • Tough gel

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Biotechnology
  • Biomedical Engineering
  • Biomaterials


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