Bio-Instructive Cues in Scaffolds for Musculoskeletal Tissue Engineering and Regenerative Medicine
In vivo, cells are presented with complex and dynamic stimuli from their surrounding microenvironment. These microenvironmental cues direct an array of cell behaviors that are critical to tissue development and regeneration, including differentiation, growth, and extracellular matrix (ECM) assembly. Tissue engineers have utilized knowledge of the microenvironment to design biomimetic, "instructive" scaffold materials that elicit an array of desired downstream cellular responses. The central challenge in bioinstructive scaffold design involves controlling cell behavior, specifically determining the signals or input instructions that are necessary to direct cells to assemble and maintain a new functional tissue for repair or replacement. Biochemical components within the microenvironment, including growth factors and cytokines, have well-established functions in regulating cell behavior, and some success has been achieved recapitulating these biochemical signals within scaffold microenvironments. However, emerging evidence has demonstrated that biophysical aspects of a cell's microenvironment may have equally important and analogous roles in regulating cell behavior. Two cellular structures, focal adhesions and adherens junctions, are thought to be key mediators in sensing and responding to the biophysical microenvironment, playing critical roles in cell migration, force-sensitive gene regulation, differentiation, and ECM assembly. Significant advancement in the field of tissue engineering requires a greater understanding of both how cells detect and interpret biophysical cues through these structures, as well as the dynamic interactions between biochemical and biophysical stimuli. This improved mechanistic understanding can then be used to guide scaffold design, explicitly targeting these structures to control downstream cell behavior and improve tissue regeneration outcomes.
Collins, KL; Gates, EM; Gilchrist, CL; Hoffman, BD
- Bio-Instructive Scaffolds for Musculoskeletal Tissue Engineering and Regenerative Medicine
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International Standard Book Number 13 (ISBN-13)
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