MCC950-loaded silk microgel-hydrogel composite scaffolds effectively modulate inflammation for improving tissue
Kieran Lau1, Angus Grant2, Alex H P Chan2
1School of Medical Sciences, University of Sydney, Sydney, NSW 2006, Australia; Sydney Biomanufacturing Incubator, University of Sydney, Sydney, NSW 2006, Australia; Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, Australia.
Acta Biomaterialia
|June 4, 2026
Summary
Silk microgel-hydrogel scaffolds with MCC950 enhance cell infiltration and reduce fibrosis for soft tissue engineering. This combination of physical and biological cues promotes tissue repair and regeneration.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Immunomodulation
Background:
- Hydrogels are attractive for soft tissue engineering but have limitations in large-volume applications, including poor cellular infiltration and fibrotic responses.
- Embedding microgels within bulk hydrogels creates microporosity, improving cell infiltration and control over cell fate.
- Encapsulating therapeutics within microgels provides bioactive cues that synergize with the scaffold's physical properties.
Purpose of the Study:
- To fabricate and evaluate silk fibroin-based hydrogel constructs incorporating MCC950-encapsulated microgels for soft tissue engineering.
- To investigate the synergistic effects of microporous architecture and targeted NLRP3 inflammasome inhibition on cellular infiltration and fibrotic response.
- To assess the bioactivity and mechanical properties of the developed microgel-hydrogel constructs.
Main Methods:
- Fabrication of silk fibroin-based hydrogel constructs with MCC950-encapsulated microgels.
- In vitro assessment of MCC950 bioactivity using human THP-1 cells.
- In vivo subcutaneous implantation in a mouse model for 2 weeks to evaluate cellular infiltration and fibrotic capsule formation.
Main Results:
- MCC950 encapsulation did not significantly alter the mechanical properties of the silk constructs.
- Eluted MCC950 retained bioactivity in vitro.
- In vivo studies showed decreased fibrous capsule formation and increased cellular infiltration, attributed to reduced NLRP3 inflammasome activity.
Conclusions:
- MCC950-encapsulated silk microgel-hydrogel constructs demonstrate potential for soft tissue engineering applications.
- A synergistic interplay between targeted NLRP3 inhibition and microporous scaffold architecture reduces fibrosis.
- These constructs promote a pro-regenerative immune microenvironment conducive to tissue remodeling.
