Melamine promotes calcium crystal formation in three-dimensional microfluidic device

Area of Science:

• Nephrology
• Toxicology
• Materials Science

Background:

• Melamine is known to cause proximal tubular (PT) cell damage.
• Combined melamine exposure with cyanuric and uric acids enhances nephrotoxicity.
• The effect of melamine on calcium phosphate (CaP) and calcium oxalate (CaOx) stone formation is not well understood.

Purpose of the Study:

• To investigate whether melamine exposure stimulates CaP and CaOx crystal formation.
• To elucidate the mechanism by which melamine influences crystal aggregation and stone formation.
• To assess the physiological relevance of melamine-induced crystal formation using microfluidic devices.

Main Methods:

• Utilized 2D and 3D microfluidic (MF) devices embedded with PT cells.
• Investigated melamine's effect on CaP, CaOx, and mixed crystal formation in a time- and concentration-dependent manner.
• Analyzed crystal stabilization, co-aggregation, and growth in the presence of melamine and preformed crystals.

Main Results:

• Melamine induced CaP, CaOx, and mixed crystal formation in a time- and concentration-dependent manner.
• Melamine stabilized crystals and promoted their co-aggregation.
• 3D MF models demonstrated potentiated crystal formation and aggregation with melamine and preformed CaP/CaOx crystals.
• Co-crystallization and activation of stone-forming pathways were identified as key mechanisms.

Conclusions:

• Melamine acts as an inducer of CaP and CaOx crystal formation.
• Melamine potentiates crystal formation and aggregation, contributing to kidney stone pathology.
• Ex-vivo models of melamine-induced crystal formation aid in understanding its role as an environmental toxicant.