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Issue 5, 2014
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Hydrogel scaffolds as in vitro models to study fibroblast activation in wound healing and disease

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Abstract

Wound healing results from complex signaling between cells and their environment in response to injury. Fibroblasts residing within the extracellular matrix (ECM) of various connective tissues are critical for matrix synthesis and repair. Upon injury or chronic insult, these cells activate into wound-healing cells, called myofibroblasts, and repair the damaged tissue through enzyme and protein secretion. However, misregulation and persistence of myofibroblasts can lead to uncontrolled accumulation of matrix proteins, tissue stiffening, and ultimately disease. Extracellular cues are important regulators of fibroblast activation and have been implicated in their persistence. Hydrogel-based culture models have emerged as useful tools to examine fibroblast response to ECM cues presented during these complex processes. In this Mini-Review, we will provide an overview of these model systems, which are built upon naturally-derived or synthetic materials, and mimic relevant biophysical and biochemical properties of the native ECM with different levels of control. Additionally, we will discuss the application of these hydrogel-based systems for the examination of fibroblast function and fate, including adhesion, migration, and activation, as well as approaches for mimicking both static and temporal aspects of extracellular environments. Specifically, we will highlight hydrogels that have been used to investigate the effects of matrix rigidity, protein binding, and cytokine signaling on fibroblast activation. Last, we will describe future directions for the design of hydrogels to develop improved synthetic models that mimic the complex extracellular environment.

Graphical abstract: Hydrogel scaffolds as in vitro models to study fibroblast activation in wound healing and disease

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Publication details

The article was received on 13 Dec 2013, accepted on 19 Feb 2014 and first published on 05 Mar 2014


Article type: Minireview
DOI: 10.1039/C3BM60319A
Citation: Biomater. Sci., 2014,2, 634-650
  • Open access: Creative Commons BY-NC license
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    Hydrogel scaffolds as in vitro models to study fibroblast activation in wound healing and disease

    M. E. Smithmyer, L. A. Sawicki and A. M. Kloxin, Biomater. Sci., 2014, 2, 634
    DOI: 10.1039/C3BM60319A

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