ResidentNet/Basic Science/New Tissue

WOUND HEALING: NEW TISSUE FORMATION
Continued...

Buds connect with contiguous buds to form loops. Loops develop a basal membrane from extracellular matrix components and then develop their own vascular buds. This process continues until -- Voila! Contact is made with an intact blood vessel and a capillary loop forms with directed blood flow. The wound is now adequately re-perfused and this has all been accomplished within days of the trauma. (Image expandable to 58K GIF).

New highly vascularized tissue has a granular appearance (which may be why it's called granulated tissue), and is recognizable by its visible pinhead-size rounded nodules. Nodules that are dark red in color and appear moist and shiny indicate good healing. Poor healing is indicated by a bluish color and a smeary fibrin appearance. (Image expandable to 36K JPEG).
As the new connective tissue is being created, existing vessels are recanalized and the old fibrin network is broken down by tissue plasminogen activator or t-PA. Collagenase, synthesized by fibroblasts, keeps collagen production in check, and has a critical function in the process of collagen maturation.

Part of the process of collagen maturation includes developing cross-links between peptide chains or between collagen molecules. It is the cross links that gives collagen and the scar strength. Also during the maturation process, collagenase breaks down inappropriately oriented collagen molecules. The result is that the new collagen, initially laid down in a chaotic, disorganized way, becomes oriented along the lines of contour stress in a manner similar to the way nature intended and nontraumatized collagen appears. (Image expandable to 54K JPEG).

Having formed abundant collagen fibers, the fibroblasts transform either into fibrocytes or myofibroblasts, the latter has contractile properties. Consequently the collagen fibers tighten. The end result of the process? Shrinking scar tissue! (Image expandable to 36K JPEG)

Ah . . .but the wound surface, you wonder. Repair of the epithelium is needed to keep the undesirables out and the vital essentials -- body fluids and electrolytes, for example -- from escaping. Reconstruction of the epithelium of the skin is a Herculean task as the epidermis is composed of four layers: the basal layer, which lies just above the dermis, the prickle cell layer, the granular layer, and finally the stratum corneum, which is composed of dead cells and keratin. (Image expandable to 46K JPEG).

Reconstruction takes place in four stages: Detachment, migration, proliferation, and differentiation. Within 24 hours of wounding, the basal cell layer of the epidermis adjacent to the wound thickens and marginal cells elongate and migrate over the wound. The cells at the advancing epithelial edge are followed by a monolayer of new epithelial cells. The new epithelial cells advance across the wound until they eventually meet epithelial cells moving in from the opposite direction. (Think of it as being like the meeting of the transcontinental railroad.) (Click on image to download Quicktime movie)

The price of wound repair is a scar, which appears reddish at first but as the connective tissue grows tauter and vascularization slows, it gradually looses color. Hair, sebaceous and sweat glands are also absent, as is the ridged pattern of the epidermis. Thus the new skin's appearance is unusually smooth. (Image expandable to 36K JPEG)

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Please see Wound Healing in Specific Tissues