Introducing Dynamicity: Engineering Stress Relaxation Into Hydrogels Via Thiol-Ene Modified Alginate for Mechanobiological in vitro Modeling of the Cornea

Antonio. J. Feliciano, Rhiannon Grant, Julia Fernandez-Perez, Stefan Giselbrecht, Matthew. B. Baker*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Developing biomaterials for corneal repair and regeneration is crucial for maintaining clear vision. The cornea, a specialized tissue, relies on corneal keratocytes, that respond to their mechanical environment. Altering stiffness affects keratocyte behavior, but static stiffness alone cannot capture the dynamic properties of in vivo tissue. This study proposes that the cornea exhibits time-dependent mechanical properties, similar to other tissues, and aims to replicate these properties in potential therapeutic matrices. First, the cornea's stress relaxation properties are investigated using nanoindentation, revealing 15% relaxation within 10 seconds. Hydrogel dynamicity is then modulated using a specially formulated alginate-PEG and alginate-norbornene mixture. The tuning of the hydrogel's dynamicity is achieved through a photoinitiated norbornene-norbornene dimerization reaction, resulting in relaxation times ranging from 30 seconds to 10 minutes. Human primary corneal keratocytes are cultured on these hydrogels, demonstrating reduced αSMA (alpha smooth muscle actin) expression and increased filopodia formation on slower relaxing hydrogels, resembling their native phenotype. This in vitro model can enable the optimization of stress relaxation for various cell types, including corneal keratocytes, to control tissue formation. Combining stress relaxation optimization with stiffness assessment provides a more accurate tool for studying cell behavior and reduces mechanical mismatch with native tissues in implanted constructs.

Original languageEnglish
Article number2300109
Number of pages18
JournalMacromolecular Bioscience
Volume24
Issue number1
Early online date1 Jul 2023
DOIs
Publication statusPublished - Jan 2024

Keywords

  • alginate
  • cornea
  • hydrogels
  • stress relaxation
  • CROSS-LINKED COLLAGEN
  • BIOMECHANICAL PROPERTIES
  • STROMAL CELL
  • TISSUE
  • KERATOCYTES
  • EXPRESSION
  • REGENERATION
  • ELASTICITY
  • SCAFFOLDS
  • MIGRATION

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