Supramolecular Engineering of Fluid Pressure in Filamentous Hybrid Double Network Hydrogels for 3D Chondrocyte Culture

Filamentous supramolecular polymers provide a modular synthetic platform that can emulate various extracellular matrix biopolymers in their structure and function. However, hydrogels based on their entangled one-dimensional nanostructures are mechanically weak and challenged in replicating the properties of native tissues that surmount cyclic compressive loads. Inspired by the structural features of load-bearing tissues such as cartilage that consist of water-rich and interconnected biopolymer networks with distinct features, we explore the in situ photopolymerization of a secondary covalent network within a filamentous supramolecular material. The resulting connectable hybrid double network hydrogels show biomimetic cartilage-like mechanical properties under dynamic loads, such as hydrostatic pressure generation and stress relaxation. We further exploit the biocompatible dithiolane-ene light-mediated crosslinking reaction to culture human primary articular chondrocytes in 3D within the materials under cyclic compressive loads. Their loading leads to significantly increased production of cartilaginous matrix proteins, sulfated-glycosaminoglycans, fibronectin I and collagen II, particularly in the photocrosslinked domains. The enclosed hybrid supramolecular and covalent double network strategy with biocompatible light-mediated crosslinking paves the way to expand the application space of filamentous supramolecular materials in 3D cell culture, providing facile access to compressive mechanical features such as hydrostatic pressure and stress relaxation essential for load-bearing cell types.