Calcium: a potential central regulator in wound healing in the skin

Abstract

Calcium has an established role in the normal homeostasis of mammalian skin and serves as a modulator in keratinocyte proliferation and differentiation. Gradients of calcium concentration increasing from 0.5 mM in the basal layer to > 1.4 mM in the stratum granulosum are consistent with migration patterns in response to minor abrasion (normal wear). Dermal fibroblasts require calcium but are approximately 100 times less sensitive than keratinocytes. Normal calcium metabolism in the skin is dependent on cell membrane and cytosolic calcium binding proteins (calmodulin, cadherins, etc.), but their modulation through parathyroid hormone, vitamin D or growth factors in normal or damaged tissue is not well documented. In wound repair, calcium is predominantly involved as Factor IV in the hemostatic phase, but it is expected to be required in epidermal cell migration and regeneration patterns in later stages of healing. Calcium alginate dressings are designed to liberate calcium early in the acute phase to promote hemostasis, but it is presently unclear whether the supplementary calcium influences the intracellular environment at later stages of wound repair, notably during the remodeling phase. Although experimental studies suggest that control of calcium is obligatory in wound management, we know very little as to how calcium in the wound bed is modulated through hormones, vitamin D, or various growth factors. Also, there is limited information as to how calcium released either from dressings, platelets, or from the circulation through the action of parathyroid hormone, growth factors or other modulators influences cell migration and remodeling in skin wounds, although experimental models suggest that management of calcium is essential in wound management. (WOUND REP REG 2002;10:271–285)