Engineering Cellular Response Using Nanopatterned Bulk Metallic Glass

Abstract

Nanopatterning of biomaterials is rapidly emerging as a tool to engineer cell function. Bulk metallic glasses (BMGs), a class of biocompatible materials, are uniquely suited to study nanopattern–cell interactions as they allow for versatile fabrication of nanopatterns through thermoplastic forming. Work presented here employs nanopatterned BMG substrates to explore detection of nanopattern feature sizes by various cell types, including cells that are associated with foreign body response, pathology, and tissue repair. Fibroblasts decreased in cell area as the nanopattern feature size increased, and fibroblasts could detect nanopatterns as small as 55 nm in size. Macrophages failed to detect nanopatterns of 150 nm or smaller in size, but responded to a feature size of 200 nm, resulting in larger and more elongated cell morphology. Endothelial cells responded to nanopatterns of 100 nm or larger in size by a significant decrease in cell size and elongation. On the basis of these observations, nondimensional analysis was employed to correlate cellular morphology and substrate nanotopography. Analysis of the molecular pathways that induce cytoskeletal remodeling, in conjunction with quantifying cell traction forces with nanoscale precision using a unique FIB-SEM technique, enabled the characterization of underlying biomechanical cues. Nanopatterns altered serum protein adsorption and effective substrate stiffness, leading to changes in focal adhesion density and compromised activation of Rho-A GTPase in fibroblasts. As a consequence, cells displayed restricted cell spreading and decreased collagen production. These observations suggest that topography on the nanoscale can be designed to engineer cellular responses to biomaterials.

Large-scale functionalization of biomedical porous titanium scaffolds surface with TiO2 nanostructures

“…The magnified SEM images (Fig. 7a1-d1) show that the BMSCs attach to the scaffold surface via filopodia, and the bonding between the filopodia and the nanostructures would guide cells to perceive and respond to the nanotopographical cues [29,30].…”

Criticality in Bulk Metallic Glass Constituent Elements

“…2 BMGs comprise transition metals that are often combined with metalloids, which are then combined in a multicomponent alloy. 3,4 The amorphous structure results in very high strength and elasticity, properties that are often paired with toughness, 5 flaw tolerance, 6 high corrosion resistance, [7][8][9][10] biocompatibility, [11][12][13] and favorable electrochemical behavior. 14 These properties have triggered wide commercial exploration of BMGs.…”

High Temperature In Situ Compression of Thermoplastically Formed Nano-scale Metallic Glass

“…1,2 In particular, metallic glasses formed at the nano-scale show attractive attributes in applications ranging from energy conversion 3,4 to bio-implants with favorable cell response. 5 Mechanical behavior of metallic glasses has been studied at the reduced length-scale with reports of a distinct size effect. 6,7 However, these deformation behavior studies have been mostly limited to room temperature.…”