The article "Advancing Synthetic Hydrogels through Nature-Inspired Materials Chemistry" by Bram G. Soliman, Ashley K. Nguyen, J. Justin Gooding, and Kristopher A. Kilian discusses the development of synthetic extracellular matrix (ECM) mimics that can replicate the complex biochemical and mechanical properties of native tissues. The authors highlight the limitations of animal-derived biomaterials and the need for xenogeneic-free alternatives suitable for organotypic models and microphysiological systems. They review the key properties of native ECM, such as viscoelasticity and matrix plasticity, and discuss recent approaches to systematically decouple and tune these properties in synthetic matrices. The article emphasizes the importance of dynamic ECM mechanics, particularly viscoelasticity and matrix plasticity, in regulating cell behavior and tissue function. It explores various design strategies for creating synthetic hydrogels that mimic these dynamic properties, including multi-network hydrogels, supramolecular chemistry, and hydrogels assembled from biological monomers. The authors also discuss the challenges and opportunities in incorporating bioactive sequences and degradability into synthetic matrices to better mimic the natural ECM. The review concludes by highlighting the potential of hybrid materials, which combine natural and synthetic components, to address the limitations of each. It also underscores the importance of computational and data-driven approaches in designing synthetic hydrogels with tailored properties for specific applications in tissue engineering and regenerative medicine.The article "Advancing Synthetic Hydrogels through Nature-Inspired Materials Chemistry" by Bram G. Soliman, Ashley K. Nguyen, J. Justin Gooding, and Kristopher A. Kilian discusses the development of synthetic extracellular matrix (ECM) mimics that can replicate the complex biochemical and mechanical properties of native tissues. The authors highlight the limitations of animal-derived biomaterials and the need for xenogeneic-free alternatives suitable for organotypic models and microphysiological systems. They review the key properties of native ECM, such as viscoelasticity and matrix plasticity, and discuss recent approaches to systematically decouple and tune these properties in synthetic matrices. The article emphasizes the importance of dynamic ECM mechanics, particularly viscoelasticity and matrix plasticity, in regulating cell behavior and tissue function. It explores various design strategies for creating synthetic hydrogels that mimic these dynamic properties, including multi-network hydrogels, supramolecular chemistry, and hydrogels assembled from biological monomers. The authors also discuss the challenges and opportunities in incorporating bioactive sequences and degradability into synthetic matrices to better mimic the natural ECM. The review concludes by highlighting the potential of hybrid materials, which combine natural and synthetic components, to address the limitations of each. It also underscores the importance of computational and data-driven approaches in designing synthetic hydrogels with tailored properties for specific applications in tissue engineering and regenerative medicine.