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									                                                                                       Kendra Sarratt
                                                                                   Tissue Engineering

                                 Cell-ECM Interactions: Wound Healing

        Imagine you are jumping a hurdle in a track race. As you approach the first hurdle, you

gather your strength to jump over it. Instead of clearing it, you trip over it, badly scraping your

shoulder. In a few weeks you look at your shoulder and see the scar that will remain for the rest

of your life. And you begin to question why you get a scar that does not go away every time you

injure yourself. It is all just a part of natural tissue engineering, illustrating interactions between

the cell and the extracellular matrix (ECM) that elicits wound healing.

        The process of wound healing in adults begins with a fibrin clot (blood clot) at the wound

site. This fibrin clot results from activation and clustering of miniature cells that lack a nucleus

and reside in the bloodstream, called platelets. Then the wound becomes inflamed and the body

produces and sends white blood cells to the wound site. Next skin cells, called keratinocytes

migrate into another ECM, the organized network of extracellular materials that is present

beyond the immediate vicinity of the plasma membrane of a cell (Karp, pg. 255). The

keratinocytes (skin cells) migrate to the ECM by first dissolving their initial attachment to a

protein called laminin in the layer between the epidermis and dermis. Then, by way of new cell

surface proteins called integrins that bind to the ECM components, the keratinocytes grasp hold

of and crawl over the provisional wound matrix and underlying wound dermis (Martin, pg.75).

Upon reaching the fibrin clot, the keratinocytes dissolve it with an enzyme. Then the

keratinocytes modify themselves by elongating and proliferating, eventually covering the wound

surface with a monolayer of skin cells. As healing progresses, tissue replaces the initial fibrin

clot in the wound and the wound physically contracts, bringing the wound margins toward one

another. During this time the fibroblasts, the major cell type that produces collagen, migrate into
the wound clot and deposit collagen. They also differentiate or transform into myofibroblasts,

cells that contract and generate force on the collagen matrix to induce a scar rich in collagen.

       Unlike embryos which have perfect wound healing (no scarring), adults during skin

regeneration go through a long-term wound healing process that results in a scar. This scarring

is due to extensive cell-ECM interactions previously discussed. Embryonic wound healing

reveals markedly different processes. The absence of scarring in embryos is not because

embryos do not possess an ECM (because they do), but rather because the keratinocytes that are

undifferentiated (or not skin cells yet) in the embryo do not move to the wound in the same way

skin cells in adults do. Unlike skin cells in adults which move to the wound by crawling (by way

of new integrins), the undifferentiated keratinocytes move to the wound by a purse-string action

that pulls the wound edges together (Martin, pg.77) without forming a scar. With this type of

movement, the undifferentiated keratinocytes unlike the skin cells in adults do not produce the

necessary myofibroblasts (see previous paragraph).

       The ECM dictates and directs wound healing. It induces stickiness, movement,

proliferation, and differentiation of the cells. By studying the ECM and how cells interact with

it, advancements in tissue engineering can be made to minimize scarring. As a result, there may

come a time when you jump over the hurdle again and fall, but your scar will be healed through

advances made in tissue engineering.


Karp, Gerald. Cell and Molecular Biology, John Wiley and Sons, Inc., pg.255. (1996).

Martin, Paul. 1997. Wound healing-aiming for perfect skin regeneration. Science. 276:75-81.


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