The extracellular matrix (ECM) plays a crucial role in regulating cell behavior, including proliferation, survival, shape, migration, and differentiation. The ECM is not static but undergoes constant remodeling, particularly during development, differentiation, and wound repair. This remodeling is influenced by the 3D environment and cellular tension transmitted through integrins. Degradation of the ECM is controlled by complex proteolytic cascades, and misregulation of these processes can lead to ECM damage, contributing to various diseases. Tissue engineering aims to replace damaged tissues with stem cells seeded on synthetic structures that mimic the ECM to restore normal cell function. The 3D environment within the stem cell niche influences stem cell self-renewal and differentiation, and understanding the dynamic relationship between cells and the ECM is essential for successful tissue engineering strategies. Key mechanisms of ECM remodeling include integrin-mediated assembly, cytoskeletal tension, and proteolytic degradation. These processes are regulated by growth factor signaling and can be influenced by the stiffness and geometry of the ECM. Recent studies have focused on designing biomimetic and bioresponsive scaffolds to mimic in vivo conditions and control cell behavior. Understanding the complex interactions between cells, the ECM, and engineered scaffolds is crucial for advancing tissue engineering and regenerative medicine.The extracellular matrix (ECM) plays a crucial role in regulating cell behavior, including proliferation, survival, shape, migration, and differentiation. The ECM is not static but undergoes constant remodeling, particularly during development, differentiation, and wound repair. This remodeling is influenced by the 3D environment and cellular tension transmitted through integrins. Degradation of the ECM is controlled by complex proteolytic cascades, and misregulation of these processes can lead to ECM damage, contributing to various diseases. Tissue engineering aims to replace damaged tissues with stem cells seeded on synthetic structures that mimic the ECM to restore normal cell function. The 3D environment within the stem cell niche influences stem cell self-renewal and differentiation, and understanding the dynamic relationship between cells and the ECM is essential for successful tissue engineering strategies. Key mechanisms of ECM remodeling include integrin-mediated assembly, cytoskeletal tension, and proteolytic degradation. These processes are regulated by growth factor signaling and can be influenced by the stiffness and geometry of the ECM. Recent studies have focused on designing biomimetic and bioresponsive scaffolds to mimic in vivo conditions and control cell behavior. Understanding the complex interactions between cells, the ECM, and engineered scaffolds is crucial for advancing tissue engineering and regenerative medicine.