Collagen Type I as a Biological Barrier Interface in Biomimetic Microfluidic Devices: Properties, Applications, and Challenges.

Collagen type I has become a practical cornerstone for constructing biologically meaningful barrier interfaces in microfluidic systems. Its fibrillar architecture, native ligand display, and susceptibility to cell-mediated remodeling support epithelial and endothelial polarization, tight junctions, and transport behaviors that are difficult to achieve with purely synthetic barrier interfaces. Recent advances pair these biological strengths with tighter engineering control. For example, ultrathin collagen barriers (tens of micrometers or less) enable faster molecular exchange and short-range signaling; gentle crosslinking and composite designs limit gel compaction and delamination under flow; and patterning/bioprinting introduce alignment, graded porosity, and robust integration into device geometries. Applications now span intestine, vasculature, skin, airway, kidney, and tumor-stroma interfaces, with readouts including transepithelial/transendothelial electrical resistance (TEER), tracer permeability, and image-based quality control of fiber architecture. Persistent constraints include batch variability, long-term mechanical drift, limited standardization of fibrillogenesis conditions, and difficulties scaling fabrication without loss of bioactivity. Priorities include reporting standards for microstructure and residual crosslinker, chips for continuous monitoring, immune-competent co-cultures, and closer collaboration across materials science, microfabrication, computational modelling, and clinical pharmacology. Thus, this review synthesizes the state-of-the-art and offers practical guidance on technological readiness and future directions for using collagen type I as a biological barrier interface in biomimetic microfluidic systems.