Nanoscale tissue engineering: spatial control over cell-materials interactions

Abstract

Cells interact with the surrounding environment by making tens to hundreds of thousands of nanoscale interactions with extracellular signals and features. The goal of nanoscale tissue engineering is to harness the interactions through nanoscale biomaterials engineering in order to study and direct cellular behaviors. Here, we review the nanoscale tissue engineering technologies for both two- and three-dimensional studies (2- and 3D), and provide a holistic overview of the field. Techniques that can control the average spacing and clustering of cell adhesion ligands are well established and have been highly successful in describing cell adhesion and migration in 2D. Extension of these engineering tools to 3D biomaterials has created many new hydrogel and nanofiber scaffolds technologies that are being used to design in vitro experiments with more physiologically relevant conditions. Researchers are beginning to study complex cell functions in 3D, however, there is a need for biomaterials systems that provide fine control over the nanoscale presentation of bioactive ligands in 3D. Additionally, there is a need for 2- and 3D techniques that can control the nanoscale presentation of multiple bioactive ligands and the temporal changes in cellular microenvironment.

Self-Assembled Peptide Amphiphile Nanofibers and PEG Composite Hydrogels as Tunable ECM Mimetic Microenvironment

“…The biological outcomes of introducing a biomaterial to the cellular microenvironment are dependent on cell−material interactions at the nanoscale level. 10 Cells can sense biochemical properties of a material such as the presence of bioactive ligands 11 as well as biophysical characteristics, including dimensionality 12 and matrix stiffness. 13 Therefore, functionalization of hydrogels is crucial for the modulation of cellular characteristics and plays an important role at biochemical and biophysical interfaces, depending on the desired cellular outcome for a specific application.…”

Engineered Contractile Skeletal Muscle Tissue on a Microgrooved Methacrylated Gelatin Substrate

“…9,10 In addition, recent developments in micropatterning and self-assembly have further enhanced the promise of hydrogels for tissue engineering and drug delivery. [11][12][13][14] Micropatterning approaches can be used to alter the behavior and fate of cells such as elongation, 15,16 differentiation, 17 and cell-cell contact and signaling. 18 Therefore, by combining micropatterning technologies and hydrogel microarchitecture, mechanical properties of scaffolds can be tuned to mimic those of the desired tissues.…”

The role of structure in the nonlinear mechanics of cross-linked semiflexible polymer networks

“…29 Understanding network mechanics and architecture at such small scale is extremely important for studies of biological cells, not only to give insights into cytoskeletal mechanics, but also because cells interact with the surrounding extracellular environment through small (micro-to nano-) scale interactions. 30 In view of these, it is crucial to base the analysis on a realistic model of semiflexible network for which the microstructure can be quantitatively parameterized. Therefore, we develop discrete 3D semiflexible networks with tunable fiber dimensions and show that the nonlinear mechanics can be explained exclusively through the structural features of the network.…”