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

Automated summary

To design effective immunomodulatory implants, controlling and understanding the interactions between biomaterial surfaces and innate immune cells is crucial. Two-photon polymerization allows for the production of surface-mounted 3D polymer objects with diverse geometries, demonstrating the importance of the interplay between architecture and materials chemistry in determining human macrophage fate. Key structure-function relationships and design rules that influence cell attachment and polarization are identified through the ChemoArchiChip, with object shape, vertex/cone angle, and size being important factors. These findings suggest that surfaces decorated with specific architectures can enhance implant performance.