Dermal Fibroblasts Modulate Migration and Phenotype of Infiltrating Monocytes in Skin-Derived Extracellular Matrix...

Area of Science:

• Biomaterials Science
• Immunology
• Wound Healing Research

Background:

• Modeling immune cell recruitment in wound microenvironments is complex.
• Existing models often lack the complexity of in vivo interactions.
• Understanding immune cell roles in early wound healing is crucial for therapeutic development.

Purpose of the Study:

• To develop and validate a novel 3D skin-derived extracellular matrix (ECM) hydrogel model.
• To investigate monocyte (THP-1) infiltration and phenotypic changes within a dermal fibroblast-populated (NHDF) matrix.
• To compare the effects of soluble fibroblast signals versus active immune cell infiltration on matrix remodeling and vascularization.

Main Methods:

• Development of a 3D biomimetic hydrogel using skin-derived ECM.
• Incorporation of human dermal fibroblasts (NHDF) and monocytes (THP-1).
• Analysis of monocyte penetration depth, myofibroblast activation (α-SMA+ cells), collagen density, and gene expression (VEGFA, TIMP, ACTA2, COL1A1).

Main Results:

• Fibroblast-derived soluble factors promoted pro-angiogenic secretomes and endothelial tube formation.
• Active immune cell infiltration restricted monocyte penetration and reduced myofibroblast activation.
• Immune infiltration preserved collagen density and shifted gene expression towards matrix stabilization (increased TIMP, decreased ACTA2/COL1A1).

Conclusions:

• The developed 3D ECM hydrogel model effectively replicates early wound healing phases.
• Immune cells act as key regulators coordinating matrix preservation and vascular support.
• This model provides a physiologically relevant platform for studying immune-matrix-stromal crosstalk in wound healing.