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Background <p>Random-pattern skin flaps are widely used in reconstructive surgery; however their viability is often compromised by ischemia-reperfusion injury, leading to inflammation, oxidative stress, and apoptosis. ROCEN, a topical formulation containing avocado/soybean unsaponifiables, has demonstrated anti-inflammatory and tissue-regenerative properties in several preclinical models.</p> Objective <p>This study aimed to evaluate the protective effects of topical ROCEN on flap viability, inflammation, apoptosis, and associated molecular signaling in a rat model of random-pattern skin flap.</p> Methods <p>Thirty-two male Wistar rats were randomly assigned to four groups: intact, untreated flap, vehicle (lecithin), and ROCEN-treated flap. A 10 × 3&#xa0;cm caudally based skin flap was created using the modified McFarlane technique. Topical treatments were applied once daily for seven consecutive days. Outcomes included flap necrosis percentage, histopathological scoring using hematoxylin and eosin staining, caspase-3 activity, and protein levels of tumor necrosis factor-alpha (TNF-α), phosphorylated mammalian target of rapamycin (p-mTOR), and phosphorylated protein kinase B (p-Akt).</p> Results <p>ROCEN treatment significantly reduced the necrotic area (23.8% vs. 56.6% in untreated group; <i>p</i> &lt; 0.0001) and improved histopathological scores (<i>p</i> &lt; 0.05). ROCEN also decreased TNF-α (<i>p</i> &lt; 0.05), caspase-3 activity (<i>p</i> &lt; 0.01), and phosphorylation of mTOR and Akt (<i>p</i> &lt; 0.05 for both), compared with untreated and vehicle groups.</p> Conclusion <p>Topical ROCEN enhanced skin flap survival by attenuating inflammation, apoptosis, and mTOR/Akt signaling. These findings support its potential as a therapeutic adjunct in reconstructive surgery. However, further studies are needed to confirm its clinical efficacy and establish the safety of its topical application in humans.</p>

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Topical ROCEN (nanoliposomal avocado/soybean unsaponifiables) enhances survival of random-pattern skin flaps through Akt/mTOR pathway modulation

  • 期刊论文

  • 发表日期：

    2025年11月12日

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  • Mohammad Mahdi Mehrabi,
  • Moein Ghasemi,
  • Amirabbas Mohammadi Hamaneh,
  • Zeinab Esmaeili,
  • Sara Ashtari,
  • Fatemeh Nejati,
  • Ramin Goudarzi,
  • Seyed Mohammad Tavangar,
  • Ahmad Reza Dehpour,
  • Alireza Partoazar

摘要

Background

Random-pattern skin flaps are widely used in reconstructive surgery; however their viability is often compromised by ischemia-reperfusion injury, leading to inflammation, oxidative stress, and apoptosis. ROCEN, a topical formulation containing avocado/soybean unsaponifiables, has demonstrated anti-inflammatory and tissue-regenerative properties in several preclinical models.

Objective

This study aimed to evaluate the protective effects of topical ROCEN on flap viability, inflammation, apoptosis, and associated molecular signaling in a rat model of random-pattern skin flap.

Methods

Thirty-two male Wistar rats were randomly assigned to four groups: intact, untreated flap, vehicle (lecithin), and ROCEN-treated flap. A 10 × 3 cm caudally based skin flap was created using the modified McFarlane technique. Topical treatments were applied once daily for seven consecutive days. Outcomes included flap necrosis percentage, histopathological scoring using hematoxylin and eosin staining, caspase-3 activity, and protein levels of tumor necrosis factor-alpha (TNF-α), phosphorylated mammalian target of rapamycin (p-mTOR), and phosphorylated protein kinase B (p-Akt).

Results

ROCEN treatment significantly reduced the necrotic area (23.8% vs. 56.6% in untreated group; p < 0.0001) and improved histopathological scores (p < 0.05). ROCEN also decreased TNF-α (p < 0.05), caspase-3 activity (p < 0.01), and phosphorylation of mTOR and Akt (p < 0.05 for both), compared with untreated and vehicle groups.

Conclusion

Topical ROCEN enhanced skin flap survival by attenuating inflammation, apoptosis, and mTOR/Akt signaling. These findings support its potential as a therapeutic adjunct in reconstructive surgery. However, further studies are needed to confirm its clinical efficacy and establish the safety of its topical application in humans.