Dithiolane-ene Photopolymerization of Covalent and Supramolecular Networks Permits Cyclic Compressive Loading in 3D Cell Culture

Filamentous supramolecular polymers provide a modular synthetic platform that emulates the biopolymers of the extracellular matrix in their structure and function. However, the materials are mechanically weak and challenged to mimic the properties of tissues that undergo cyclic compressive loading like cartilage. Herein, we explore the use of light-mediated chain growth polymerization of dithiolane and dithiolane-ene to simultaneously crosslink a network of nanoscale supramolecular filaments with covalent polymer macromonomers, yielding hybrid double network hydrogels that can sustain dynamic compression in 3D cell culture. Benefitting from the energy dissipation mechanisms accessible to supramolecular materials, they show cartilage-like mechanical characteristics, such as biomimetic stress responses to compression and relaxation that can be tuned according to component ratios and concentrations using light. 3D culture of human primary articular chondrocytes in the photocrosslinked hydrogels displayed increased deposition of sulfated-glycosaminoglycans. Exploiting the photoreactive macromonomers, we mechanically pattern the materials at cell relevant length scales and apply cyclic compressive loads up to 14 days. The enclosed covalent network fortification strategy combined with bioorthogonal light-mediated crosslinking provides a base to tune the mechanics of filamentous supramolecular biomaterials in both space and time for 3D cell culture to mimic tissues under compressive loads in development and disease.