This review explores the potential of biomaterial-based mechanical regulation to facilitate scarless wound healing and the regeneration of functional skin appendages. It highlights two main approaches: creating an optimal scarless environment using biomaterials with specific biophysical properties and harnessing mechanical forces to enhance cellular plasticity. The review discusses the role of mechanical cues in scar formation and wound healing, emphasizing the importance of understanding the underlying mechanisms. It also delves into the biophysical characteristics of biomaterials that modulate extracellular signaling, alter cellular epigenetic states, support cell migration, and promote tissue ingrowth. The review further examines the mechanisms of mechano-transduction, including the involvement of integrin-focal adhesion kinase (FAK) signaling, the cytoskeleton, and the linker of nucleoskeleton and cytoskeleton (LINC) complex. Additionally, it explores the influence of biomaterials on extracellular signaling, cellular epigenetics, cell migration, and tissue ingrowth. The review concludes by discussing the adaptability of biomaterials to the wound environment and their potential in optimizing regenerative healing.This review explores the potential of biomaterial-based mechanical regulation to facilitate scarless wound healing and the regeneration of functional skin appendages. It highlights two main approaches: creating an optimal scarless environment using biomaterials with specific biophysical properties and harnessing mechanical forces to enhance cellular plasticity. The review discusses the role of mechanical cues in scar formation and wound healing, emphasizing the importance of understanding the underlying mechanisms. It also delves into the biophysical characteristics of biomaterials that modulate extracellular signaling, alter cellular epigenetic states, support cell migration, and promote tissue ingrowth. The review further examines the mechanisms of mechano-transduction, including the involvement of integrin-focal adhesion kinase (FAK) signaling, the cytoskeleton, and the linker of nucleoskeleton and cytoskeleton (LINC) complex. Additionally, it explores the influence of biomaterials on extracellular signaling, cellular epigenetics, cell migration, and tissue ingrowth. The review concludes by discussing the adaptability of biomaterials to the wound environment and their potential in optimizing regenerative healing.