Recent progress in the manipulation of biochemical and biophysical cues for engineering functional tissues

Abstract

Tissue engineering (TE) is currently considered a cutting-edge discipline that offers the potential for developing treatments for health conditions that negatively affect the quality of life. This interdisciplinary field typically involves the combination of cells, scaffolds, and appropriate induction factors for the regeneration and repair of damaged tissue. Cell fate decisions, such as survival, proliferation, or differentiation, critically depend on various biochemical and biophysical factors provided by the extracellular environment during developmental, physiological, and pathological processes. Therefore, understanding the mechanisms of action of these factors is critical to accurately mimic the complex architecture of the extracellular environment of living tissues and improve the efficiency of TE approaches. In this review, we recapitulate the effects that biochemical and biophysical induction factors have on various aspects of cell fate. While the role of biochemical factors, such as growth factors, small molecules, extracellular matrix (ECM) components, and cytokines, has been extensively studied in the context of TE applications, it is only recently that we have begun to understand the effects of biophysical signals such as surface topography, mechanical, and electrical signals. These biophysical cues could provide a more robust set of stimuli to manipulate cell signaling pathways during the formation of the engineered tissue. Furthermore, the simultaneous application of different types of signals appears to elicit synergistic responses that are likely to improve functional outcomes, which could help translate results into successful clinical therapies in the future.

Keywords: biochemical cues; biophysical cues; differentiation; induction factors; tissue engineering.

FIGURE 1

Biochemical stimulating factors involved in manipulating cell fate decisions in tissue engineering. Biochemical factors including growth factors, cytokines, small molecules, polynucleotides, and ECM components induce activation of various downstream regulatory molecules in intracellular signaling pathways which alter gene expression and subsequently lead to fate determination and different cell responses such as differentiation, growth, proliferation, migration, and ECM remodeling. CSFs, colony‐stimulating factors; EGF, epidermal growth factor; FGF, fibroblast growth factor; NTFs, neurotrophic factors; PDGF, platelet‐derived growth factor; TGF, transforming growth factor; VEGF, vascular endothelial growth factor

FIGURE 2

Biophysical stimulating factors involved in manipulating cell fate decisions in tissue engineering. Various biophysical stimuli can be applied to cells to obtain the most preferable cell behavior and characteristics; magnetic, thermal, ultrasound, irradiation, electric, and mechanical (shear stress, tensile, fluid flow, hydrostatic pressure, and compression forces) induction are among these stimuli. Moreover, various surface topographies give rise to different cells responses. Stimulatory factors upon affecting sensitive receptors of the cell surface, contribute to rearrangement and reorientation of cell cytoskeletons. Once in the nucleus, the signals generated by cytoskeleton rearrangement leads to alternation in the gene expression which determines the cell behavior consequently

FIGURE 3

Various aspects of surface topography, Different types of mechanical stresses, and electrical stimulations in tissue engineering. (Top) Different surface topographic textures have different impacts on cell activities and responses. Four different aspects of topography demonstrated in the figure, are surface patterns, roughness, alignment, and pore size. (Middle) Mechanical forces in cell niches such as compression, shear, fluid flow, hydrostatic pressure, and tensile can be sensed by cells through diverse mechanisms. The direction of arrows illustrates the direction of mechanical force. (Below) Electrical stimulation along with parameters involved in electric current play crucial roles in the cell behavior. Three methods to induce electric current are direct coupling, capacitive coupling, and inductive coupling