局部递送4-氨基吡啶促进烧伤创面皮肤再生。

Govindaraj Ellur, Meenakshi Kamaraj, John Elfar, Prem Kumar Govindappa, Johnson V John
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引用次数: 0

摘要

烧伤创面是一种常见的创伤性损伤,损害细胞功能,阻碍愈合过程,经常导致严重的皮肤损失。虽然自体皮肤移植被认为是治疗烧伤的金标准,但由于供体部位的发病率和对大量组织的要求,其广泛应用受到限制。传统的伤口敷料和治疗往往不能保证完全恢复。4-氨基吡啶(4-AP)最初被fda批准用于治疗多发性硬化症,也被证明通过全身给药转化角化细胞和成纤维细胞来加速烧伤伤口愈合。然而,长期系统使用4-AP会导致显著的副作用。在这项研究中,我们的目的是重新利用4-AP治疗皮肤烧伤创面,通过使用laponite-明胶凝胶配方局部递送。该方法可实现烧伤部位非侵入性和局部给药。我们评估了4-AP凝胶剪切减薄行为的物理性质、药物释放动力学、生物相容性和使用划痕试验的功能性伤口愈合。此外,我们的体内实验表明,负载4-AP的凝胶通过促进皮肤烧伤后的再上皮化和毛囊再生,促进成纤维细胞向肌成纤维细胞转化,从而加速伤口愈合,从而支持细胞外基质重塑。这种4-AP凝胶的新应用为目前的烧伤创面治疗提供了一种有希望的替代方案,可能会改善烧伤患者的预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Topical Delivery of 4-Aminopyridine Enhances Skin Regeneration in Burn Wounds.

Burn wounds are a common traumatic injury that impair cellular function and hinder the healing process, often resulting in significant skin loss. While autologous skin grafting is considered the gold standard for treating burns, its widespread use is limited due to donor site morbidity and the requirement for large amounts of tissue. Traditional wound dressings and treatments often fail to ensure complete recovery. Being initially FDA-approved to treat multiple sclerosis, 4-aminopyridine (4-AP) has also been shown to accelerate burn wound closure by transforming keratinocytes and fibroblasts when administered systemically. However, prolonged systemic use of 4-AP can lead to significant side effects. In this study, we aimed to repurpose 4-AP for treating skin burn wounds by delivering it topically using a laponite-gelatin gel formulation. This method allows for non-invasive and localized drug delivery on burn wound site. We evaluated the physical properties of the 4-AP gel shear thinning behavior, drug release kinetics, biocompatibility, and functional wound closure using a scratch assay. Moreover, our in vivo experiments showed that the 4-AP loaded gel accelerates wound healing by enhancing re-epithelialization and hair follicle regeneration and promoting fibroblast to myofibroblast transformation, which supports extracellular matrix remodeling after skin burns. This novel application of the 4-AP gel could offer a promising alternative to current burn wound therapies, potentially leading to improved outcomes for burn patients.

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