The spaces between these loops are filled by cells of various kinds, the most important being the fibroblasts, which are destined to form cicatricial fibrous tissue.  These fibroblasts are large irregular nucleated cells derived mainly from the proliferation of the fixed connective-tissue cells of the part, and to a less extent from the lymphocytes and other mononuclear cells which have migrated from the vessels.  Among the fibroblasts, larger multi-nucleated cells—­giant cells—­are sometimes found, particularly when resistant substances, such as silk ligatures or fragments of bone, are embedded in the tissues, and their function seems to be to soften such substances preliminary to their being removed by the phagocytes.  Numerous polymorpho-nuclear leucocytes, which have wandered from the vessels, are also present in the spaces.  These act as phagocytes, their function being to remove the red corpuscles and fibrin of the original clot, and this performed, they either pass back into the circulation in virtue of their amoeboid movement, or are themselves eaten up by the growing fibroblasts.  Beyond this phagocytic action, they do not appear to play any direct part in the reparative process.  These young capillary loops, with their supporting cells and fluids, constitute granulation tissue, which is usually fully formed in from three to five days, after which it begins to be replaced by cicatricial or scar tissue.

Formation of Cicatricial Tissue.—­The transformation of this temporary granulation tissue into scar tissue is effected by the fibroblasts, which become elongated and spindle-shaped, and produce in and around them a fine fibrillated material which gradually increases in quantity till it replaces the cell protoplasm.  In this way white fibrous tissue is formed, the cells of which are arranged in parallel lines and eventually become grouped in bundles, constituting fully formed white fibrous tissue.  In its growth it gradually obliterates the capillaries, until at the end of two, three, or four weeks both vessels and cells have almost entirely disappeared, and the original wound is occupied by cicatricial tissue.  In course of time this tissue becomes consolidated, and the cicatrix undergoes a certain amount of contraction—­cicatricial contraction.

Healing of Epidermis.—­While these changes are taking place in the deeper parts of the wound, the surface is being covered over by epidermis growing in from the margins.  Within twelve hours the cells of the rete Malpighii close to the cut edge begin to sprout on to the surface of the wound, and by their proliferation gradually cover the granulations with a thin pink pellicle.  As the epithelium increases in thickness it assumes a bluish hue and eventually the cells become cornified and the epithelium assumes a greyish-white colour.

Clinical Aspects.—­So long as the process of repair is not complicated by infection with micro-organisms, there is no interference with the general health of the patient.  The temperature remains normal; the circulatory, gastro-intestinal, nervous, and other functions are undisturbed; locally, the part is cool, of natural colour and free from pain.