Biomedical Engineering Reference
In-Depth Information
Chapter 5
Wound Healing Assay
5.1 Biological Introduction
Cell migration plays a critical role in a diverse array of processes both in phys-
iological conditions and in pathological situations. In developing embryos, the
coordinated movement of cells of different origin, over short and long distance
paths, is fundamental for organogenesis, as defects at all stages of such a coop-
erative migration lead to severe embryonic malformations, resulting in drastic
overall consequences [220]. In adult organisms, cell movement is instead essen-
tial in wound healing, where epidermal tissues are repaired by the progressive
extension of tongues of epidermal cells, which completely close the lesions,
as well as in the cases of inflammations. On the other hand, cell migration is
involved in chronic inflammatory diseases and artheriosclerosis, and is respon-
sible for the primary dissemination of tumors and its following metastatization
[337]. It is also important in biomedical engineering applications, where bioac-
tive scaffolds act as physical support structures and insoluble regulators for
cell activity (i.e., adhesion, growth, and differentiation) in in vivo or in vitro
regenerations of various tissues, such as cartilage, skin, or peripheral nerves
[63, 178, 373, 418].
An accurate description of cell migratory capacity, as well as a deep analy-
sis of the complex multilevel underpinning processes, are therefore pivotal is-
sues in developmental biology, giving rise to a number of experimental models.
In particular, given the outstanding amount and heterogeneity of approaches,
a first and useful differentiation can be made following their scale of inter-
est. At the cellular and subcellular level, a large set of experimental works
have taken into account the dynamics of the movement of single individu-
als, providing a good understanding of the driving mechanical and molecular
mechanisms, as the activation of integrin receptors [382], the activity of focal
adhesion structures [188], or the cytoskeletal polarization [267, 311, 328]. At
the multicellular level, the migration of populations has been analyzed, draw-
ing the attention on both the migratory capacities of entire cultures and on
the cooperative behaviors and interactions of single individuals.
In this regard, one of the most common experimental models is the wound
healing assay, which measures the overall motility of a cell population by
quantifying its invasion of a planar substrate. In particular, it consists of the
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