Generalizing Gelatin Methacryloyl Granular Hydrogel Fabrication Using Stable Microgels with Predictable Stiffness

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Gelatin methacryloyl granular hydrogel scaffolds (GelMA GHS) offer advantages over bulk hydrogels due to tunable, cell-scale void spaces.
• Conventional GelMA GHS fabrication involves physical crosslinking followed by chemical crosslinking, which is hindered by microgel dissolution at physiological temperatures.
• The influence of sequential crosslinking on microgel properties and scaffold formation is not fully understood, particularly concerning the balance between microgel stability and covalent assembly.

Purpose of the Study:

• To develop a generalized method for fabricating GelMA GHS using stable microgels via a two-step photocrosslinking approach.
• To establish a phase diagram correlating microgel stability (step 1 photocrosslinking) with scaffold formation (step 2 photocrosslinking).
• To create a regression model predicting mechanical properties based on fabrication variables for GelMA GHS.

Main Methods:

• A two-step photocrosslinking strategy was employed for GelMA microgel and scaffold fabrication.
• A phase diagram was constructed to map microgel stability against scaffold formation capability.
• Box-Behnken design was utilized to develop a regression model for predicting mechanical properties.

Main Results:

• A novel two-step photocrosslinking method was established for creating stable GelMA GHS.
• A phase diagram was developed, elucidating the relationship between microgel stability and scaffold assembly.
• A predictive regression model for mechanical properties was successfully generated.

Conclusions:

• The developed two-step photocrosslinking approach enables the fabrication of stable GelMA GHS from microgels.
• This method overcomes the limitations of conventional fabrication, allowing for in situ formation of GelMA GHS at physiological temperatures.
• The findings facilitate the development of GelMA GHS for diverse translational biomedical applications.