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An Injectable, Shape-Retaining Collagen Hydrogel Cross-linked Using Thiol-Maleimide Click Chemistry for Sealing

Jenny Rosenquist1, Matilde Folkesson1, Lisa Höglund1

  • 1Macromolecular Chemistry, Department of Chemistry - Ångström Laboratory, Uppsala University, Box 538, Uppsala 751 21, Sweden.

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Summary

This study introduces a new injectable collagen hydrogel using thiol-maleimide click chemistry. This advanced biomaterial offers tunable properties and excellent biocompatibility for regenerative medicine and corneal repair applications.

Keywords:
click chemistrycollagen hydrogelcorneal perforationsinjectable hydrogelshape-retainingthiol-Michael addition reaction

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Tissue Engineering

Background:

  • Injectable hydrogels are promising for regenerative medicine and minimally invasive applications.
  • Existing collagen hydrogels have limitations including poor biocompatibility, swelling, and unsuitable gelation kinetics.
  • Extracellular matrix-based hydrogels offer cell adhesion, biocompatibility, and enzymatic degradability.

Purpose of the Study:

  • To design and characterize a novel injectable collagen hydrogel addressing limitations of current collagen-based materials.
  • To develop a biomaterial suitable for *in vivo* injection, with tunable mechanical properties and enhanced biocompatibility.
  • To evaluate the hydrogel's potential for corneal repair and as a tissue sealant.

Main Methods:

  • Covalent modification of collagen with acetyl thiol groups.
  • Cross-linking using thiol-maleimide click chemistry.
  • Characterization of injectability, swelling, mechanical properties, and *in vitro* cell viability with human corneal epithelial cells.

Main Results:

  • The developed hydrogel is injectable for up to 72 hours, exhibits no significant swelling, and maintains shape for over a year.
  • Mechanical properties are tunable by adjusting reactant stoichiometries, a feature previously seen only in synthetic hydrogels.
  • *In vitro* studies confirmed excellent biocompatibility with sustained viability and proliferation of corneal epithelial cells.
  • The hydrogel demonstrated strong adhesion to soft tissues, comparable to fibrin glue, and potential as a corneal sealant.

Conclusions:

  • The thiol-modified collagen hydrogel offers a versatile and biocompatible platform for regenerative medicine.
  • Its tunable properties and injectability make it suitable for various applications, including prefabricated implants and injectable fillers.
  • The hydrogel shows significant potential as a sealant for corneal repair, offering an alternative to existing adhesives.