A microfluidic dermal fibroblast–macrophage co-culture on a chip linking inflammatory signalling to barrier-associated function

Abstract

Here, we report a microfluidic dermal fibroblast–macrophage co-culture on-chip that directly links macrophage-driven inflammatory signalling to dermal barrier function within a three-dimensional collagen microenvironment. The platform integrates spatially compartmentalized co-culture of dermal fibroblasts and macrophages separated by a micropillar-confined collagen type I matrix, enabling non-contact paracrine communication while preserving extracellular matrix (ECM) architecture. Upon lipopolysaccharide stimulation, the system rapidly reproduced of acute inflammation within 6 h and 12 h, including elevated nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) secretion, increased permeability to both 10 kDa and 70 kDa FITC–dextran, and disruption of fibronectin organization. The measured permeability coefficient closely matched reported in vivo skin values, supporting physiological relevance. Suppression of inflammatory mediators using a nanostructured lipid carrier encapsulating Zingiber cassumunar and Kaempferia parviflora extracts resulted in dose-dependent reductions in NO and TNF-α, accompanied by restoration of dermal thickness and ECM integrity. Importantly, biochemical inhibition of macrophage activation translated into structural recovery of the fibroblast-embedded matrix, demonstrating a clear coupling between immune signalling and tissue-level remodeling. This microfluidic platform provides a rapid, physiologically relevant, and animal-free system for mechanistic investigation of dermal inflammation and evaluation of anti-inflammatory therapeutics.