Haptotaxis (from Greek ἅπτω (hapto, "touch, fasten") and τάξις (taxis, "arrangement, order")) is the directional motility or outgrowth of cells, e.g. in the case of axonal outgrowth, usually up a gradient of cellular adhesion sites or substrate-bound chemoattractants (the gradient of the chemoattractant being expressed or bound on a surface, in contrast to the classical model of chemotaxis, in which the gradient develops in a soluble fluid.). These gradients are naturally present in the extracellular matrix (ECM) of the body during processes such as angiogenesis or artificially present in biomaterials where gradients are established by altering the concentration of adhesion sites on a polymer substrate. Clinical Significance Haptotaxis plays a major role in the efficient healing of wounds. For example, when corneal integrity is compromised, epithelial cells quickly cover the damaged area by proliferation and migration (haptotaxis). In the corneal stroma, keratocytes within the wounded area undergo apoptosis, leaving the stroma devoid of cells that must be replaced. Keratocytes surrounding the wounded area proliferate and become fibroblasts that migrate to fill the wounded area. This creates a healthy environment with myofibroblasts and extracellular matrix. This is known as light backscattering or subepithial haze. When there is injury to an epithelial cell heptotaxis occurs, which is highly influenced by the cell's velocity, which is in turn influenced by direction of cell motility. Cells migrate easily and quickly in packs, so when one cell moves the rest follow in response to the gradient and initial cell movement. Mechanical effects like the buildup of tensile forces may play an important role for both division as well as motility of cells in tissue. Methods of Study As defined above, haptotaxis is the motility of cells up a gradient of substrate bound molecules. There is a wide variety of procedures to set up this gradient in vitro for the study of haptotaxis. The two main categories can be classified into either continuous or digital. Both types are relatively easy to produce, but digital gradients give more accurate concentration calculations. Overall, the methods in use currently can be improved to mirror the in vivo environment more, as the resolution of the gradients is not as sharp in vitro as they are in vivo. Also, biological gradients have the ability to change geometry, which current models in vitro cannot mimic. These gradients are useful in gaining understanding of the basics of haptotaxis, but because of the complex