The Effect of Exogenous Zinc Concentration on the Responsiveness of MC3T3-E1 Pre-Osteoblasts to Surface Microtopography: Part I (Migration)

Abstract

Initial cell-surface interactions are guided by the material properties of substrate topography. To examine if these interactions are also modulated by the presence of zinc, we seeded murine pre-osteoblasts (MC3T3-E1, subclone 4) on micropatterned polydimethylsiloxane (PDMS) containing wide (20 µm width, 30 µm pitch, 2 µm height) or narrow (2 µm width, 10 µm pitch, 2 µm height) ridges, with flat PDMS and tissue culture polystyrene (TC) as controls. Zinc concentration was adjusted to mimic deficient (0.23 µM), serum-level (3.6 µM), and zinc-rich (50 µM) conditions. Significant differences were observed in regard to cell morphology, motility, and contact guidance. We found that cells exhibited distinct anisotropic migration on the wide PDMS patterns under either zinc-deprived (0.23 µM) or serum-level zinc conditions (3.6 µM). However, this effect was absent in a zinc-rich environment (50 µM). These results suggest that the contact guidance of pre-osteoblasts may be partly influenced by trace metals in the microenvironment of the extracellular matrix.

Proliferation and osteogenic response of MC3T3‐E1 pre‐osteoblastic cells on porous zirconia ceramics stabilized with magnesia or yttria

“…The transformation of a cell from spherical to spread‐out shape, observed on both ceramics, is important for cell survival and it is acknowledged that cells undergo significant changes when attaching and spreading on substrates . However, bivalent trace metals in the microenvironment of biomaterial surfaces influence initial cell‐surface interactions and may also affect the responsiveness of osteoblasts to microtopography, as it has been shown for zinc ions . In addition, Mg ions play important roles in the binding interactions of fibronectin and vitronectin, which may explain the different morphology of cells cultured on MgSZ …”

“…34 However, bivalent trace metals in the microenvironment of biomaterial surfaces influence initial cell-surface interactions and may also affect the responsiveness of osteoblasts to microtopography, as it has been shown for zinc ions. 35 In addition, Mg ions play important roles in the binding interactions of fibronectin and vitronectin, which may explain the different morphology of cells cultured on MgSZ. 36 A fully spread, flat cell morphology, was reported to be better with respect to cell proliferation and differentiation.…”

Enhanced osteogenic differentiation of MC3T3‐E1 cells on grid‐topographic surface and evidence for involvement of YAP mediator

“…Scaffolds or materials should be designed to mimic the extracellular matrix (ECM) in vivo as much as possible in order to improve the cells performance of appropriate function. [1][2][3] Numerous studies have shown that several signal pathways initiated from stimulation in the microenvironment can regulate cell behaviors such as cell adhesion, proliferation, and differentiation. [4][5][6] Thus, the topographical feature of the scaffold surface to which cells adhere is an important characteristics for cell differentiation and tissue regeneration.…”

“…To develop new biomaterials in bone tissue engineering, it is important to find a more effective scaffold with bone conduction properties, but many challenges exist. Scaffolds or materials should be designed to mimic the extracellular matrix (ECM) in vivo as much as possible in order to improve the cells performance of appropriate function . Numerous studies have shown that several signal pathways initiated from stimulation in the microenvironment can regulate cell behaviors such as cell adhesion, proliferation, and differentiation .…”

The Effect of Exogenous Zinc Concentration on the Responsiveness of MC3T3-E1 Pre-Osteoblasts to Surface Microtopography: Part II (Differentiation)

“…Depriving pre-osteoblasts of zinc reduces their differentiation capacity by decreasing ALP and osteopontin expression, as well as calcium deposition [ 14 ]. We have previously demonstrated that levels of exogenous zinc can disrupt the interaction of pre-osteoblasts with topographical surface features, particularly in their actin organization and contact guidance behavior [ 16 ]. Because contact guidance is closely linked to osteogenic differentiation and mineralization [ 17 – 19 ], zinc may also have an effect on the differentiation of osteoblasts cultured on various topographies.…”