Biophysical and Biochemical Cues of Biomaterials Guide Mesenchymal Stem Cell Behaviors

Abstract

Mesenchymal stem cells (MSCs) have been widely used in the fields of tissue engineering and regenerative medicine due to their self-renewal capabilities and multipotential differentiation assurance. However, capitalizing on specific factors to precisely guide MSC behaviors is the cornerstone of biomedical applications. Fortunately, several key biophysical and biochemical cues of biomaterials that can synergistically regulate cell behavior have paved the way for the development of cell-instructive biomaterials that serve as delivery vehicles for promoting MSC application prospects. Therefore, the identification of these cues in guiding MSC behavior, including cell migration, proliferation, and differentiation, may be of particular importance for better clinical performance. This review focuses on providing a comprehensive and systematic understanding of biophysical and biochemical cues, as well as the strategic engineering of these signals in current scaffold designs, and we believe that integrating biophysical and biochemical cues in next-generation biomaterials would potentially help functionally regulate MSCs for diverse applications in regenerative medicine and cell therapy in the future.

Conductive Scaffolds for Bone Tissue Engineering: Current State and Future Outlook

“…Evaluation of the development of new bone tissue shows that this process can be largely attributed to the presence of biophysical and biochemical cues within the surrounding microenvironment. Biophysical cues such as porosity and substrate stiffness have enabled BTE scaffolds to better regenerate tissue following injury and other losses of natural bone, as well as to determine MSCs lineage fate in vitro [ 108 , 109 ]. Upon implantation, scaffolds come into direct contact with native tissue; their structure and surface characteristics play a tremendous role in their overall integration within the body [ 110 , 111 ].…”

Bioprintable Lung Extracellular Matrix Hydrogel Scaffolds for 3D Culture of Mesenchymal Stromal Cells

“…Stiffness of the scaffold in 3D culture has been shown to influence the direction of differentiation of MSCs [ 37 ], but the impact on their immunomodulatory properties is still to be elucidated. Stiffness of ECM-derived hydrogels is lower than the stiffness of the native tissue, but it can be modified by chemical processes, such as genipin or photo-crosslinking [ 38 , 39 ].…”

Mesenchymal stem cells from biology to therapy

“…This essentially prevascularized the construct, demonstrating the possibility of creating an already vascularised scaffold, made to fit unique anatomical structures [62]. For further information on the use of 3D scaffolds for MSC delivery, tissue regeneration, directing cell function, immunomodulation and genetic modification, please refer to recent reviews [63][64][65][66].…”