Mechanosensation is universal to all living creatures, and mechanical forces govern various biological processes via mechanotransduction. Existing mechano-responsive hydrogels can exhibit strain-stiffening, self-healing, and shear-thinning, and these properties are usually endowed by specific modifications to the chemical nature of the hydrogel systems. A current gap in technology is whether mechano-responsive degradable hydrogels can be developed, and if this capacity can be mediated by materials embedded within hydrogels, instead of the chemical modification of functional groups. Mechano-responsive degradable hydrogels have gamechanging potential for biosensors, bioactive factor delivery, tissue engineering, and biomaterial science. For example, such hydrogels could serve as biosensors and reporters for swelling and increased pressure and enable the release of pain relief and/or anti-inflammatory drugs under compressive stress in cartilage. Alternatively, hydrogel scaffolds replacing damaged tissue under mechanical load, such as bone, could degrade in response to compressive stress as the tissue regenerates.