Initiating the inflammatory phase of incisional healing prior to tissue injury.

Abstract

The time required for incisional healing accounts for the majority of postoperative pain and convalescence. Impaired healing prolongs the process further. If a method for accelerating acute incisional wound healing could be developed, patients would benefit from decreased wound failure and an earlier return to their premorbid condition. In a rat dermal model, cytokine or vehicle infiltration prior to incision was performed using a single dose or four daily doses preincision. Planned incision sites were primed with the proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) or platelet-derived growth factor BB (PDGF-BB) in an effort to activate the inflammatory phase of healing prior to wounding. At the time of incision closure, one half of the incisions were treated with transforming growth factor beta(2) (TGF-beta(2)). Incisional sites were biopsied and stained with hematoxylin and eosin and immunohistochemistry for inflammatory cells and fibroblast populations and breaking strength was measured. Priming skin with GM-CSF or PDGF-BB mimicked the early inflammatory phase of wound healing. Macrophage staining (EB1) and fibroblast staining (vimentin) were significantly increased prior to incision. Inflammatory priming as well as priming coupled with TGF-beta(2) at the time of the incision closure synergistically improved breaking strength. This study demonstrates that sequential therapy consisting of priming of tissue with an inflammatory cytokine followed by application of a proliferative cytokine at the time of incision closure nearly doubles the breaking strength of an acute wound. By manipulating the inflammatory and early proliferative phases of wound healing with tissue growth factors, it may be possible to accelerate acute wound repair and shift the wound healing trajectory to the left.