Self‐assembly of Structured Colloidal Gels for High Resolution 3d Micropatterning of Proteins at Scale

Abstract

Self‐assembly, the spontaneous ordering of components into patterns, is widespread in nature and fundamental to generating function across length scales. Morphogen gradients in biological development are paradigmatic as both products and effectors of self‐assembly and various attempts have been made to reproduce such gradients in biomaterial design. To date, approaches have typically utilised top‐down fabrication techniques which, while allowing high resolution control, are limited by scale and require chemical cross‐linking steps to stabilise morphogen patterns in time. Here, we develop a bottom‐up approach to protein patterning based on a novel binary reaction‐diffusion process where protein's function as diffusive reactants to assembly a nanoclay‐protein composite hydrogel. Using this approach, we were able to generate scalable and highly stable 3D patterns of target proteins down to sub‐cellular resolution through only physical interactions between clay nanoparticles and the proteins and ions present in blood. Patterned nanoclay gels were able to guide cell behaviour to precisely template bone tissue formation in vivo. Our results demonstrate the feasibility of stabilising 3D gradients of biological signals through self‐assembly processes and open up new possibilities for morphogen‐based therapeutic strategies and models of biological development and repair.

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