The Efficacy of Platelet-rich Plasma Gel and Topical Estradiol Alone or in Combination on Healing of Full-thickness Wounds
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Estrogens can indirectly influence the proliferative phase of wound healing.27–29
In normal wounds, synthesis of heat-shock protein, PDGF, and FGF is stimulated within 24 hours after dermal injury, then VEGF, PGDF, FGF, and EGF are synthesized. Increased synthesis returns to normal levels between days 7 and 14 of injury parallel to wound healing.8 In the present study, angiogenesis was determined a significant increase in PRP gel + estradiol group and estradiol group on the 14th day (P < 0.05). Estrogen is assumed to be responsible for the rapid increase of angiogenesis on day 14. The application of PRP to the full-thickness skin wounds improved overall healing by reducing contraction as well as showing a trend toward increasing epithelization rate and stimulating angiogenesis. However, these differences did not seem to occur in the low platelet count (PRP [3.92-fold]) treatment. This was likely due to the small sample size with insufficient power to detect the difference. Two other possible explanations are the inability of this volume to cover the wound serving as a tissue scaffold completely and possible reduction in the amount of growth factors released.
Studies on ovariectomized rat models have shown that the number of macrophages in full-thickness wounds (with substantial loss) significantly decrease on days 3 and 5, and that the inflammatory phase of the healing was delayed in the absence of estrogen.30,31 This also shows that the presence of estrogen shapes the inflammatory phase and increases the number of macrophages. Macrophages, in addition to their known functions, take part in the synthesis of growth factors such as interleukin-1 (IL-1), PDGF, TGF-β, epidermal growth factor, and insulin-like growth factor, thus contributing to the proliferation phase.30 In the present study, macrophage counts were not significantly different between the groups on days 7, 14, and 21. Considering these results, one can hypothesize that the substances used did not exert a notable effect on macrophage counts.
Granulation tissue is particularly important for the healing of large wounds. Fibroblasts are crucial elements of granulation tissue. The proliferation of fibroblasts is influenced by several factors such as inflammatory products, chemotactic factors, and growth factors.33 In the present study, fibrosis was nearly the same on day 7 in all groups and an increase tendency was observed afterwards. There was no significant difference between the treatment groups and sterile saline solution group could be noted during the rest of the study. However, another study34 found significant increases in fibroblast and collagen production in PRP-treated wounds because PRP contains growth factors such as PDGF and TGF-β, which can stimulate cell replication and extracellular matrix production.35 Specifically, Henderson et al34 showed that PRP increased fibroblast proliferation and collagen production in porcine burn wounds. The reason for such a discrepancy is not clear, but the high covariance of the present study was not sensitive enough to corroborate statistically significant differences in fibroblasts that might account for a portion of it.
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