Dynamic, Reconfigurable, and Hierarchical Biosynthetic Composites via Collagen Self‐Assembly within Highly Crowded Microgel Pastes

The fabrication of a new class of biomimetic biomaterials is reported using nanostructured microgel pastes formed from "overpacked" assemblies of ultrasoft poly(N-isopropyl acrylamide-co-acrylic acid) microgels and their composites with collagen. Despite the solid-like nature of microgel pastes, collagen fibrillogenesis is robust and rapid, with a 3D collagen network forming throughout the paste volume. Structural organization within the composite is interrogated via a suite of microscopy methods, while rheological characterization provides insight into the static and dynamic mechanical properties of the materials. Long-range fibrillogenesis is enabled by local crowding, dynamics, and spatial reconfigurability of pastes at the colloidal length-scale, and by liquid-liquid phase separation during fibril formation, features that mimic the dynamic reorganization of natural extracellular matrix. In vitro 3D cell culture studies illustrate that the paste is non-toxic, permeable to nutrients, and permissive to cell invasion, while collagen fibers present sites for cell attachment and spreading. Together, these results suggest the platform's potential in the development of tissue scaffolds that mimic crowded and dynamic biological tissues. These materials address the need for new approaches to biomaterials that offer dynamic, bio-integrative environments for tissue healing and regenerative medicine via synthetic and spatial control from the polymer to the macroscopic length scales.