The next “domino” to fall in the healing cascade is the domino of the proliferative phase.

The purpose of this step of the healing cascade is to both repair vascular integrity, and mend the tissue defect.  Vascular integrity is restored through neoangiogenesis.  The cellular mediator of neoagniogeneis is keratinocyte through elaboration of angiogenic factors including such major players as vascular endothelial growth factor (VEGF).

Granulation tissue formation is a fibroblast dependent process, whereby converted “wound fibroblasts”are the predominant cellular component.  Through this fibroblast dependent process granulation tissue forms through the deposition of collagen, restoring extracellular matrix.  Wound fibroblast migration is dependent upon viable integrin binding sites in the extracellular matrix.this process is mediated by such growth factors is transforming growth factor beta (TGFB) and platelet derived growth factor (PDGF)

As this is the step in which the healing, aggressively happens, I think this is an opportune time to discuss wound healing goals. There are really 2 major goals one being regeneration, and the alternative goal of scar tissue formation. The ultimate goal in wound healing is regeneration which restores normal tissue function and normal tissue appearance.  Wounds that involve the epidermis are superficial dermis typically will heal through the process of regeneration. A less desirable but acceptable goal is scar tissue formation.  Most wound I encounter go beyond the deep dermis into subcutaneous and beyond, healing in these cases occurs by formation of a scar.  Scar tissue formation is an acceptable goal as it restores a functional barrier, although a barrier with less tensile strength than regenerated skin.