Significance
Since the mechanical properties of native extracellular matrix (ECM) change over time during development, healing and homeostatic processes, it may be valuable to have the capacity to dynamically control the mechanics of biomaterials used in tissue engineering and regenerative medicine applications to better mimic this behavior. Unlike previously reported biomaterials whose mechanical properties can be changed by the user only a limited number of times, this system provides the capacity to induce unlimited alterations to the mechanical properties of an engineered ECM for 3D cell culture. This study presents a strategy for on-demand dynamic and reversible control of materials' mechanics by single and dual-crosslinking mechanisms using oxidized and methacrylated alginates. By demonstrating direct changes in encapsulated human mesenchymal stem cell morphology, proliferation and chondrogenic differentiation in response to multiple different dynamic changes in hydrogel mechanics, we have established a repeatedly reversible 3D cellular mechanosensing system. This system provides a powerful platform tool with a wide range of stiffness tunability to investigate the role of dynamic mechanics on cellular mechanosensing and behavioral responses.
Statement of significance
Since the mechanical properties of native extracellular matrix (ECM) change over time during development, healing and homeostatic processes, it may be valuable to have the capacity to dynamically control the mechanics of biomaterials used in tissue engineering and regenerative medicine applications to better mimic this behavior. Unlike previously reported biomaterials whose mechanical properties can be changed by the user only a limited number of times, this system provides the capacity to induce unlimited alterations to the mechanical properties of an engineered ECM for 3D cell culture. This study presents a strategy for on-demand dynamic and reversible control of materials' mechanics by single and dual-crosslinking mechanisms using oxidized and methacrylated alginates. By demonstrating direct changes in encapsulated human mesenchymal stem cell morphology, proliferation and chondrogenic differentiation in response to multiple different dynamic changes in hydrogel mechanics, we have established a repeatedly reversible 3D cellular mechanosensing system. This system provides a powerful platform tool with a wide range of stiffness tunability to investigate the role of dynamic mechanics on cellular mechanosensing and behavioral responses.