Controlled Nanoscale Topographies for Osteogenic Differentiation of Mesenchymal Stem Cells

Abstract

Nanotopography with length scales of the order of extracellular matrix elements offers the possibility of regulating cell behavior. Investigation of the impact of nanotopography on cell response has been limited by inability to precisely control geometries, especially at high spatial resolutions, and across practically large areas. In this paper, we demonstrate well-controlled and periodic nanopillar arrays of silicon and investigate their impact on osteogenic differentiation of human mesenchymal stem cells (hMSCs). Silicon nanopillar arrays with critical dimensions in the range of 40-200 nm, exhibiting standard deviations below 15% across full wafers were realized using self-assembly of block copolymer colloids. Immunofluorescence and quantitative polymerase chain reaction (RT-qPCR) measurements reveal clear dependence of osteogenic differentiation of hMSCs on the diameter and periodicity of the arrays. Further, the differentiation of hMSCs was found to be dependent on the age of the donor. While osteoblastic differentiation was found to be promoted by the pillars with larger diameters and heights independent of donor age, they were found to be different for different spacings. Pillar arrays with smaller pitch promoted differentiation from a young donor, while a larger spacing promoted those of an old donor. These findings can contribute for the development of personalized treatments of bone diseases, namely novel implant nanostructuring depending on patient age.

<p>Directional Osteo-Differentiation Effect of hADSCs on Nanotopographical Self-Assembled Polystyrene Nanopit Surfaces</p>

“…Another study suggested that nanopillar arrays (silicon nanopillar arrays with critical dimensions in the range of 40-200 nm) can enhance osteogenic differentiation of human mesenchymal stem cells. 14 Although different nanostructure surfaces are used, the specific cell responses to nanoscale topography are confirmed in the present study. Moreover, the present study offers a new nanopit structure with directional osteo-differentiation effect of hADSCs.…”

“…Recently, the nanoscale surface topography was proven to have highly promising effects on regulating survival, proliferation, migration, and differentiation of adult MSCs. 13,14 Implant materials with nanostructured surfaces have shown promising applications in orthopedic surgical field. 15 The nanoscale surface morphology remarkably determines cellular responses, which have an important role in the optimization of medical implant biocompatibility.…”

F-actin Regulates Osteoblastic Differentiation of Mesenchymal Stem Cells on TiO2 Nanotubes Through MKL1 and YAP/TAZ

“…In biomedicine, surface topography is also able to direct cellular behaviors, including cell migration, adhesion, proliferation, and differentiation. The latest studies reveal that nanoscale topography can direct mesenchymal stem cells (MSCs) to differentiate into osteoblasts so as to reinforce early osseointegration [9][10][11][12]. It is even reported that combined micro-and nano-scale surface modification can cause MSCs to differentiate into contractile smooth muscle cells [13].…”

Nanoplasmonic Arrays with High Spatial Resolutions, Quality, and Throughput for Quantitative Detection of Molecular Analytes

“…A representative AFM image recorded in the tapping mode is shown in Figure 3b. The characterization is critical for each batch of samples, and it is possible to scale the process to several batches of wafers [41]. Points A, B, C, and D correspond to four positions representing systematically increasing radial distances from the center to the edge of the wafer.…”