Converting Muscle-mimetic Biomaterials to Cartilage-like Materials

Load-bearing tissues, such as muscle and cartilage, exhibit mechanical properties that often combine high elasticity, high toughness and fast recovery, despite their different stiffness ([~]100 kPa for muscles and one to several MPa for cartilage).1-7 The advance in protein engineering and protein mechanics has made it possible to engineer protein-based biomaterials to mimic soft load-bearing tissues, such as muscles.8-10 However, it is challenging to engineer protein biomaterials to achieve the mechanical properties exhibited by stiff tissues, such as articular cartilage,6,11 or to develop stiff synthetic extracellular matrices for cartilage stem/progenitor cell differentiation12. By employing physical entanglements13 of protein chains and force-induced protein unfolding,14,15 here we report the engineering of a highly tough and stiff protein hydrogel to mimic articular cartilage. By crosslinking an engineered artificial elastomeric protein from its unfolded state, we introduced chain entanglement into the hydrogel network. Upon renaturation, the entangled protein chain network and forced protein unfolding entailed this single network protein hydrogel with superb mechanical properties in both tensile and compression tests, showing a Youngs modulus of [~]0.7 MPa and toughness of 250 kJ/m3 in tensile testing; and [~]1.7 MPa in compressive modulus and toughness of 3.2 MJ/m3. The energy dissipation in both tensile and compression tests is reversible and the hydrogel can recovery its mechanical properties rapidly. Moreover, this hydrogel can withstand a compression stress of >60 MPa without failure, amongst the highest compressive strength achieved by a hydrogel. These properties are comparable to those of articular cartilage, making this protein hydrogel a novel cartilage-mimetic biomaterial. Our study opened up a new potential avenue towards engineering protein hydrogel-based substitute for articular cartilage, and may also help develop protein biomaterials with superb mechanical properties for applications in soft actuators and robotics.