Innate immune cell instruction using micron-scale 3D objects of varied architecture and polymer chemistry: The ChemoArchiChip

To design effective immunomodulatory implants, innate immune cell interactions at the surface of biomaterials need to be controlled and understood. The architectural freedom two-photon polymerization is used produce arrays surface-mounted, geometrically diverse 3D polymer objects. This reveals importance interplay between architecture materials chemistry in determining human macrophage fate vitro. ChemoArchiChip identifies key structure-function relationships rules from machine learning models build a mechanistic understanding attachment polarization. Object shape, vertex/cone angle, size are drivers attachment. Particular shapes found heavily modulate pro- or anti-inflammatory polarization, while triangular pyramids drastically reduce even eliminate Caveola-dependent endocytosis principal mechanism by which cells respond objects with sharp points; i.e., low angles. discovery these putative points surfaces decorated architectures augment implant performance.