Stem Cell Mechanobiology and the Role of Biomaterials in Governing Mechanotransduction and Matrix Production for Tissue Regeneration

Abstract

Mechanobiology has underpinned many scientific advances in understanding how biophysical and biomechanical cues regulate cell behavior by identifying mechanosensitive proteins and specific signaling pathways within the cell that govern the production of proteins necessary for cell-based tissue regeneration. It is now evident that biophysical and biomechanical stimuli are as crucial for regulating stem cell behavior as biochemical stimuli. Despite this, the influence of the biophysical and biomechanical environment presented by biomaterials is less widely accounted for in stem cell-based tissue regeneration studies. This Review focuses on key studies in the field of stem cell mechanobiology, which have uncovered how matrix properties of biomaterial substrates and 3D scaffolds regulate stem cell migration, self-renewal, proliferation and differentiation, and activation of specific biological responses. First, we provide a primer of stem cell biology and mechanobiology in isolation. This is followed by a critical review of key experimental and computational studies, which have unveiled critical information regarding the importance of the biophysical and biomechanical cues for stem cell biology. This review aims to provide an informed understanding of the intrinsic role that physical and mechanical stimulation play in regulating stem cell behavior so that researchers may design strategies that recapitulate the critical cues and develop effective regenerative medicine approaches.

From the Matrix to the Nucleus and Back: Mechanobiology in the Light of Health, Pathologies, and Regeneration of Oral Periodontal Tissues

“…Physical ECM properties are key determinants of cell behavior in vitro and in vivo. The stiffness of the ECM, quantified by the Young's modulus, as well as viscoelastic properties, spatial arrangement of adhesion points, and other geometric constraints, influence cellular responses through MT and other signaling hubs [14,47,48]. This means that ECM composition, homeostasis and MT are tightly coupled and are, therefore, highly interdependent [49].…”

“…Beneath biochemical factors and ion currents, mechanical cues are transmitted from the ECM to the cell and vice versa within a process called mechanotransduction (MT). The same principles apply to cell-to-cell contact sites, where cellular traction forces are transmitted between adjacent cells [11][12][13][14][15].…”

“…On the molecular level, MT relies on membrane-embedded cellular receptor proteins that sense and bind to extracellular ligands, which are either ECM proteins in the case of cell-to-matrix adhesion or cell-bound ligands in the case of cell-to-cell contacts [11][12][13][14][15][16].…”

Mechanobiological conceptual framework for assessing stem cell bioprocess effectiveness

“…While the impact of forces and mechanical environment on the structure and function of stem cells has long been appreciated (Ivanovska et al, 2015;Liu et al, 2010;Maul et al, 2011;Mendelson and Frenette, 2014;Naqvi and McNamara, 2020), the importance of mechanical forces in bioprocessing has only recently been investigated. The potential sources of cell-to-cell variability to bioprocesses-described here as intrinsic (intra-cellular) noise, extrinsic (inter-cellular) noise, or external (environmental) noise-have been difficult to investigate because the evidence assessing the effect of external environmental fluctuations on a system is limited (Hilfinger and Paulsson, 2011).…”

Designer Scaffolds for Interfacial Bioengineering

“…The physical environment affects many cellular processes including differentiation, migration, force generation, proliferation, spreading, alignment, and gene expression [28][29][30][31] . The interplay between the physical characteristics of the microenvironment and biochemical signaling is complex, and extensive research has been dedicated to elucidating the mechanisms responsible for these phenomena [32][33][34][35][36] . These insights have highlighted a need to develop strategies for the fabrication of biomimetic constructs that more closely match the mechanical properties of the native environment of the cell 37 .…”