Regulation and Directing Stem Cell Fate by Tissue Engineering Functional Microenvironments: Scaffold Physical and Chemical Cues

Abstract

It is well known that stem cells reside within tissue engineering functional microenvironments that physically localize them and direct their stem cell fate. Recent efforts in the development of more complex and engineered scaffold technologies, together with new understanding of stem cell behavior in vitro, have provided a new impetus to study regulation and directing stem cell fate. A variety of tissue engineering technologies have been developed to regulate the fate of stem cells. Traditional methods to change the fate of stem cells are adding growth factors or some signaling pathways. In recent years, many studies have revealed that the geometrical microenvironment played an essential role in regulating the fate of stem cells, and the physical factors of scaffolds including mechanical properties, pore sizes, porosity, surface stiffness, three-dimensional structures, and mechanical stimulation may affect the fate of stem cells. Chemical factors such as cell-adhesive ligands and exogenous growth factors would also regulate the fate of stem cells. Understanding how these physical and chemical cues affect the fate of stem cells is essential for building more complex and controlled scaffolds for directing stem cell fate.

Figure 1

(a, d) Different 3D-printed bone tissue engineering scaffolds. Fused deposition modeling of polymer bone tissue models. (b, e) Direct extrusion 3D printing of calcium phosphate bioceramics. (c, f) Selected laser melting 3D printing of titanium femoral head nail prosthesis [12, 18, 29, 35].

Figure 2

SEM micrographs of different electrospun nanofibers. (a) Electrospun PCL nanofiber [50]. (b) Electrospun-aligned PLGA nanofiber [51]. (c) Electrospun-aligned PLGA/gelatin nanofiber [51]. (d) Electrospun PLA nanofiber [52]. (e) Electrospun silk fibroin-gelatin nanofiber (50 : 50) [52]. (f) Electrospun silk fibroin-gelatin nanofiber (70 : 30) [52].

Figure 3

Typical orderly micropatterned scaffold surface. HA bioceramic micropatterned surface with regular small concaves (a) and larger concaves (b) [57]. HA ceramics with spherical array (c) [61]. Micropatterned vertical grooves (d) and inclined grooves (e) [59]. Ordered hexagonal-shape patterns (f) [61]. Quadrate convexes with smaller space (g) and larger space (h) [60]. Grid-shaped patterns (i) [63].

Figure 4

The stiffness affecting the fate of stem cell in vivo, adopted figure from Butcher et al. [98]; the brain is softer than bone, and stem cells are more likely to differentiate into neural differentiation on a soft cell matrix. By contrast, osteogenic differentiation is more likely to occur on scaffolds, which are harder and have material properties similar to those of newly formed bones.

Figure 5

Nanotechnology on different materials with different topographies. (a) Porous silicon fabricated by electrochemical etching, adopted figure from Wang et al. [123]. (b) Colloidal lithography fabricated by self-assembly and sputtering [105]. (c) Nanogrooves fabricated by UV-assisted capillary force lithography [124]. (d) TiO₂ nanotube fabricated by anodization [125]. (e) Binary colloidal crystals fabricated by self-assembly [126]. (f) Nanopillars (polyurethane acrylate) fabricated by nanoimprinting [127].

Figure 6

Compared with 2D environment, 3D environment could carry growth factors, maintain stiffness, and promote stem cell differentiation [135].

Figure 7

Mechanical signal transduction. Mechanical signaling influences the proliferation and differentiation of stem cells through integrins, ion channels, receptors or exogenous growth factors, and complex intracellular pathways [171].