Extracellular-Matrix-Mimetic Hydrogels by Using Nanomaterials

Matrigel, a tumor-derived basement membrane extract, has been commercially used in the field of cell culture and tissue engineering due to its extracellular-matrix-mimetic (ECM-mimetic) properties. However, its batch-to-batch variability and limited mechanical tunability hinder reproducibility and clinical translation. To overcome these issues, synthetic ECM-mimetic hydrogels have been developed to improve reproducibility and biocompatibility. While they are effective in mimicking ECMs, these materials must go beyond passive replication by implementing the complex functionalities of the ECM. The integration of nanomaterials with hydrogel could address this need by reinforcing mechanical properties, enabling various functionalities, and featuring dynamic responsiveness. In this review, we present the evolution from Matrigel to ECM-mimetic hydrogels and ECM-mimetic hydrogel nanocomposites, exploring their key advancements and challenges. We will discuss the advantages and disadvantages of the transition from Matrigel to ECM-mimetic hydrogels and ECM-mimetic hydrogel nanocomposites, along with cases that have addressed Matrigel's limitations and added new functionalities. Furthermore, we discuss future directions for the design of the ECM-mimetic hydrogels, emphasizing how nanotechnology strategies can drive innovation in tissue engineering and regenerative medicine.