Background. Transforming growth factor β1 (TGF-β1) is an effective accelerator of soft tissue repair in both normal and impaired healing models; however, its in vivo mechanism of action remains unclear. Modern radiation techniques can create unique healing deficits, allowing for a more specific definition of tissue response to growth factor therapy. In the rat linear skin incision model, cobalt 60 photon beam total body irradiation (TBI), 800 rads, causes a marked depression of circulating monocytes and largely spares the skin tissue. Megavoltage electron beam surface irradiation (SI), 2500 rads, markedly impairs surface healing while sparing the bone marrow. With these models of selective healing deficits, the ability of TGF-β1 to accelerate tissue repair directly in the absence of circulating macrophage precursors (TBI) or in the presence of damaged dermal fibroblasts (SI) was evaluated. Methods. Adult male Sprague-Dawley rats were randomly assigned to groups of TBI, SI, or nonirradiated sham controls and received radiation 2 days before wounding. Paired linear full-thickness skin incisions were created and a single dose of TGF-β1 (2 μg/wound) or vehicle control was applied to each wound. Results. Both radiation techniques produced a marked healing deficit when assessed on postwounding days 7 and 12. TBI treatment was characterized by severe monocytopenia, confirmed by a tissue macrophage-specific immunohistochemical technique. On days 7 and 12 after wounding, TGF-β1 significantly accelerated soft tissue repair and wound-breaking strength in the TBI-treated rats, demonstrating an ability to directly promote the induction of collagen synthesis in the absence of monocytes/macrophages. In contrast, TGF-β1 was unable to reverse the SI-induced healing deficit characterized by impaired function of dermal fibroblasts. Conclusions. These in vivo observations provide further evidence for a direct mechanism of action by TGF-β1 on collagen synthesis by wound fibroblasts during soft tissue repair.
|Original language||English (US)|
|Number of pages||7|
|State||Published - Jan 1993|
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