Architecting a partial thickness cartilage substitute with mimetic, self-assembling hydrogels

Restoration of partial thickness chondral defects (PTCDs) may be achieved with a synthetic substitute that mimics the discrete mechanical properties of the superficial and transitional chondral layers. Moreover, innate adhesivity of the two components would enable the facile construction and integrity of this bilayered system. Herein, we report a PTCD bilayered substitute formed by triple network (TN) hydrogels that leverage electrostatic charge interactions to achieve mechanical mimicry and self-assembly. TN hydrogels were formed with a polyampholyte 3rd network of five different charge composition (<i>i.e.</i>, ratio of cationic and anionic monomers), as well as two crosslink densities. All TN hydrogels exhibited cartilage-like hydration. A single superficial-like chondral layer TN hydrogel, with a somewhat more anionic 3rd network, was identified having mimetic compressive modulus (∼1.8 MPa) and strength (∼13 MPa). Additionally, three transitional-like chondral layer candidates were identified, including two TN hydrogels with a more cationic 3rd network in addition to the TN hydrogel with a 'cationic-only' 3rd network. The adhesivity of the superficial layer and the three transitional layer candidates was found to be robust (∼>100 kPa), wherein the bilayered construct exhibited cohesive rather than adhesive failure.