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.
Highlights
To expedite progress toward clinical deployment of tissue engineering applications, biomaterial optimization is moving from traditional ad hoc approaches to combinatorial/high-throughput methods [1]
Types of gradient samples constructed for biological studies and the observed changes in cellular response in gradient material samples will be covered
It is possible that the current RGD concentration gradient hydrogel adhesion studies do not present RGD concentration levels as high as the dendritic cell study did to the cells, that the different cell types used have different responses to RGD concentrations, or that additional material or mechanical property differences between studies are altering the results
Summary
To expedite progress toward clinical deployment of tissue engineering applications, biomaterial optimization is moving from traditional ad hoc approaches to combinatorial/high-throughput methods [1]. A major advantage of using a gradient material sample approach over design of experiments and arrays to understand cell–material interactions and optimize matrix conditions for biological response is the reduced variation in sample preparation between conditions in the test range because they are housed in a single sample This reduced variation enables greater resolution of regions of cellular transitions, allowing for more accurate identification of thresholds in the test range. As a number of material properties are known to affect cellular behavior, a number of gradient hydrogel systems, High-Throughput 2018, 7, 1 which will be discussed below, have been developed to tune cellular response It is, important to note that the aqueous nature of hydrogels makes their material properties susceptible to changes in the local environment (bioactive signaling interactions, cells, ions, etc.) compared to other tissue engineering matrix types, such as foams and nanofibers. These changes can complicate analysis of the cellular response because multiple material properties can change at once, but through characterization of the matrices can improve analysis of cellular response
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