# Gellan Gum Methacryloyl-Based Composite Hydrogels to Promote Murine Primary Macrophage Differentiation

**Authors:** Ana Letícia Rodrigues Costa, Jhonatan Rafael de Oliveira Bianchi, Lucimara Gaziola de La Torre, Sang Won Han

PMC · DOI: 10.1021/acsomega.5c07273 · ACS Omega · 2025-12-15

## TL;DR

This study explores composite hydrogels made from gellan gum and fibrin to support macrophage differentiation and function for tissue engineering.

## Contribution

The novel contribution is the development of GMa-based hydrogels with optimized fibrinogen concentration to promote macrophage differentiation.

## Key findings

- Hydrogels with higher fibrinogen (7–9 mg/mL) showed increased stiffness and porosity while maintaining high cell viability.
- Primary macrophages retained their phenotype and expressed key markers like F4/80, iNOS, and arginase-1 in the hydrogels.
- The hydrogels effectively promoted M1–M2 macrophage differentiation, indicating their potential as scaffolds for immune cell response.

## Abstract

Injectable hydrogels
made from biopolymers present promising
platforms
for tissue engineering and wound healing applications, particularly
because of their tunable mechanical properties and the ability to
support cell growth. In this work, we developed and characterized
composite hydrogels composed of gellan gum methacryloyl (GMa), unmodified
gellan gum (GG), and fibrin (Fib) to investigate their mechanical
properties on Raw 264.7 and primary murine macrophages. The mechanical
properties and porosity of the hydrogels were tailored by varying
the ratio of GGMa and fibrinogen. Hydrogels with higher concentrations
of fibrinogen (7–9 mg/mL) exhibited increased stiffness and
enhanced porosity and maintained a high cell viability for both lineages.
Immunocytochemistry confirmed that primary macrophages preserved their
phenotype, expressing crucial markers (F4/80, iNOS, and arginase-1),
indicating that the GMa-based hydrogels with optimized fibrinogen
concentration can serve as effective scaffolds for macrophage response,
promoting M1–M2 macrophage differentiation.

## Linked entities

- **Proteins:** Adgre1 (adhesion G protein-coupled receptor E1), NOS2 (nitric oxide synthase 2), Arg1 (arginase 1)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Arg1 (arginase, liver) [NCBI Gene 11846] {aka AI, Arg-1, PGIF}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, Adgre1 (adhesion G protein-coupled receptor E1) [NCBI Gene 13733] {aka DD7A5-7, EGF-TM7, Emr1, F4/80, Gpf480, Ly71}
- **Chemicals:** GG (MESH:C048288), GMa (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12756827/full.md

## References

29 references — full list in the complete paper: https://tomesphere.com/paper/PMC12756827/full.md

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Source: https://tomesphere.com/paper/PMC12756827