Rei Ogawa - Total Scar Management: From Lasers to Surgery for Scars, Keloids, and Scar Contractures

From the dawn of man to the present day, traumatic injuries have persisted as a major cause of morbidity and mortality. Even as recently as the Civil War in the United States, up to 24% of upper extremity amputations and 88% of amputations just below the hip resulted in death []. Increased insight into the cellular and molecular mechanisms underpinning wound healing holds promise for improving the lives of these individuals and driving the development of new therapies. Accordingly, in this chapter we will focus attention on understanding the mammalian response to injury, basic mechanisms of healing, local and systemic factors affecting healing, and recent advances in the management of chronic wounds and scars.

Healing is not a science, but the intuitive art of wooing natureW.H. Auden []

The survival of a living organism depends on its ability to maintain a stable internal environment, known as homeostasis. When homeostasis is perturbed by environmental changes, also known as stressors, complex biological systems within the organism work in tandem to reestablish equilibrium via the process of growth adaptation [].

As a homeostatic regulatory response, growth adaptation depends on the type of stressor, its magnitude, and the type of cell, tissue, or organ affected. Take, for example, the response of skeletal muscle to mechanical stress in the form of strength training. As the mechanical stress increases, muscle cells respond in kind by increasing the number of contractile proteins, myofibrils, and energy stores leading to an overall growth in cell size known as hypertrophy []. The response to increased stress need not be binary, however, as seen in the gravid uterus which undergoes both hypertrophy and hyperplasia in response to mechanical and hormonal stimuli in order to better accommodate a growing fetus.

In contrast to the above processes, tissues experiencing a decrease in stress diminish in size, or atrophy, due to disuse or withdrawal of trophic factors such as oxygen, nutrients, and hormonal stimulation. Mechanisms of atrophy include a decrease in cell size or number. The former occurs via autophagy (Ancient Greek for self-eating), in which cytoplasmic contents are enzymatically degraded and recycled within lysosomes, as well as the ubiquitin-proteosome pathway which targets short-lived (and often damaged) proteins for destruction []. A decrease in cell number, on the other hand, can be achieved by an organized program of cell death known as apoptosis or the chaotic destruction of large groups of cells in response to injury as seen in necrosis.

External changes in mechanical stress can lead to changes in cell size or number, while certain environmental exposures can induce metaplasia, a reversible transformation of one differentiated cell type into another type better suited to handle this exposure. The most common forms of metaplasia involve changes in surface epithelium. A classic example is the alteration in the lining of the lower esophagus in the setting of persistent reflux esophagitis, known as Barretts esophagus. The typical lining of the esophagus is squamous epithelium which can slough off without damaging underlying layers and is, therefore, ideal for overcoming the mechanical friction of a food bolus. When there is chronic inflammation due to persistent acid reflux, however, epithelial stem cells are reprogrammed into mucus-secreting columnar cells like those seen in the small intestine which are better able to withstand an acidic environment. Although this may be beneficial in the short term, this process of cellular reprogramming can be maladaptive if the inciting exposure is not resolved. With time, cellular growth and proliferation becomes disordered, known as