Gradient Material Strategies for Hydrogel Optimization in Tissue Engineering Applications

Abstract

Although a number of combinatorial/high-throughput approaches have been developed for biomaterial hydrogel optimization, a gradient sample approach is particularly well suited to identify hydrogel property thresholds that alter cellular behavior in response to interacting with the hydrogel due to reduced variation in material preparation and the ability to screen biological response over a range instead of discrete samples each containing only one condition. This review highlights recent work on cell-hydrogel interactions using a gradient material sample approach. Fabrication strategies for composition, material and mechanical property, and bioactive signaling gradient hydrogels that can be used to examine cell-hydrogel interactions will be discussed. The effects of gradients in hydrogel samples on cellular adhesion, migration, proliferation, and differentiation will then be examined, providing an assessment of the current state of the field and the potential of wider use of the gradient sample approach to accelerate our understanding of matrices on cellular behavior.

Keywords: cell–material interface; combinatorial method; gradient.

Figure 1

Schematic of gradient profiles in material samples.

Figure 2

Staining of neural specific βIII tubulin (red) with nuclear stain (blue) in human induced pluripotent stem cell derive neural stem cells after 14 days of neural differentiation culture on polyethylene glycol hydrogels possessing a continuous gradient in Young's modulus. Scale bar is 100 µm across whole gradient and 50 µm enlargement. Modified and reprinted with permission of John Wiley & Sons, Inc. from [36].

Figure 3

mRNA expression of βIII tubulin (TUJ1) in mouse embryonic stem cells and human induced pluripotent stem cell derive neural stem cells over a time course of neural differentiation on polyethylene glycol hydrogels possessing continuous concentration gradients of N-cadherin-derived peptide HAVDI (His-Ala-Val-Asp-Ile). GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; NCAD: N-cadherin; hiPSC: human induced pluripotent stem cell; NSC: neural stem cells. Reprinted with permission from [85] with permission from Elsevier, Copyright 2016 Elsevier, Ltd., and [55], Copyright 2017 American Chemical Society.