Porous Polymeric Nanofilms for Recreating the Basement Membrane in an Endothelial Barrier-on-Chip

Area of Science:

• Biomaterials Engineering
• Tissue Engineering
• Microfluidics

Background:

• Organs-on-chips (OoCs) require accurate basement membrane (BM) models for physiological relevance.
• Existing artificial membranes (PES, PC) lack the thinness, elasticity, and permeability of natural BMs.
• Limitations hinder the accurate replication of tissue interfaces and cellular functions in vitro.

Purpose of the Study:

• To develop and characterize porous poly(d,l-lactic acid) (PDLLA) nanofilms as artificial basement membranes for OoCs.
• To evaluate the performance of PDLLA nanofilms in supporting cell culture and mimicking physiological barriers.
• To demonstrate the integration of PDLLA nanofilms into microfluidic devices for advanced in vitro modeling.

Main Methods:

• Fabrication of transparent PDLLA nanofilms (∼200 nm thick) using roll-to-roll gravure coating and phase separation.
• Characterization of nanofilm properties, including thickness, elasticity, and pore size distribution (0.4–1.6 μm).
• Integration of PDLLA nanofilms into microfluidic chips for cell culture and barrier formation studies.

Main Results:

• PDLLA nanofilms are 60x thinner and 27x more elastic than PES membranes, with controlled porosity.
• Human umbilical vein endothelial cells (HUVECs) cultured on PDLLA showed 97% viability, enhanced adhesion, and proliferation.
• Functional endothelial barrier formed on PDLLA, evidenced by increased transendothelial electrical resistance and blocked 150 kDa dextran diffusion.

Conclusions:

• Porous PDLLA nanofilms effectively replicate natural basement membrane characteristics for organs-on-chips.
• These artificial BMs enhance the physiological relevance of in vitro models, improving cell culture and drug discovery.
• PDLLA nanofilms show potential for mimicking complex tissue interfaces like the blood-brain barrier in OoCs.