OPSALC: On-ParticleSolvent-Assisted Lipid Coatingto Create Erythrocyte Membrane-like Coatings with Improved Hemocompatibility

Particles are essential building blocks in nanomedicine and cell engineering. Their administration often involves blood contact, which demands a hemocompatible material profile. Coating particles with isolated cell membranes is a common strategy to improve hemocompatibility, but this solution is nonscalable and potentially immunogenic. Cell membrane-like lipid coatings are a promising alternative, as lipids can be synthesized on a large scale and used to create safe cell membrane-like supported bilayers. However, a method to controllably and scalably lipid-coat a wide range of particles has remained elusive. Here, an on-particle solvent-assisted lipid coating (OPSALC) method is introduced as an innovative technique to endow various types of particles with cell membrane-like coatings. Coating formation efficiency is shown to depend on lipid concentration, buffer addition rate, and solvent:buffer ratio, as these parameters determine lipid assembly and lipid–surface interactions. Four lipid formulations with various levels of erythrocyte membrane mimicry are explored in terms of hemocompatibility, demonstrating a reduced particle-induced hemolysis and plasma coagulation time. Interestingly, formulations with higher mimicry levels show the lowest levels of complement activation and highest colloidal stability. Overall, OPSALC represents a simple yet scalable strategy to endow particles with cell membrane-like lipid coatings to facilitate blood-contact applications.