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新型成纤维细胞浸渍羟乙基纤维素凝胶在大鼠全层烧伤模型中的伤口愈合作用:一项临床前研究

The Wound-Healing Effect of a Novel Fibroblasts-Impregnated Hydroxyethylcellulose Gel in a Rat Full-Thickness Burn Model: A Preclinical Study.

作者信息

Novosad Yury A, Shabunin Anton S, Enukashvily Natella I, Supilnikova Olga V, Konkina Anastasia I, Semenova Natalia Yu, Yatsemirsky Gleb S, Zinoviev Evgenii V, Rodionova Kristina N, Kryshen Kirill L, Borodina Antonina Yu, Makarov Alexander Yu, Fedyuk Andrey M, Nilov Alexander D, Chikulaeva Elena V, Konkova Lidiya S, Chustrak Irina S, Traxova Veronika V, Safonov Platon A, Vissarionov Sergey V, Prikhodko Egor M, Yurkevich Yury V

机构信息

Professor G.I. Gaivoronsky Laboratory of Experimental Traumatology and Orthopedics with Vivarium, H. Turner National Medical Research Center for Children's Orthopedics and Trauma Surgery, 196603 St. Petersburg, Russia.

Institute of Biomedical Systems and Biotechnologies, Peter the Great St. Petersburg Polytechnic University, 195251 St. Petersburg, Russia.

出版信息

Biomedicines. 2024 Sep 28;12(10):2215. doi: 10.3390/biomedicines12102215.

Abstract

The objective of this study was to assess the efficacy of a cell-containing wound dressing based on fibroblasts in hydroxyethylcellulose (HEC) gel for the local treatment of deep partial-thickness and/or full-thickness skin burns in an animal model. The rats (male Wistar, n = 100) were subjected to a full-thickness thermal burn (16 cm). Radical necrectomy was performed one day after the burn. Three days later, the rats were randomly assigned to one of four groups: group 1 (no treatment), group 2 (chloramphenicol and methyluracil ointment, a routine clinical treatment), group 3 (a gel without cells, mock treatment), and group 4 (a dermal fibroblast-impregnated HEC gel). The treatment lasted for five days. The wound-healing process was evaluated by planimetric, cytologic, histologic, and immunohistochemical methods. The differences in the rate of wound healing and the characteristics of wound cytology were identified. In the group 4, a regenerative type of cytogram was revealed, characterized by a significantly increased number of fibroblastic cells in comparison to samples from non-treated and mock-treated animals. Biopsy samples of burn wounds from animals in the group 4l demonstrated the presence of mature granulation tissue and a large number of microvessels. The repair process was stimulated, as evidenced by the increased thickness of newly formed granulation tissue and epidermis in the wound zone, elevated cellularity, and enhanced re-epithelialization activity. The number of Ki-67-positive proliferating cells was significantly higher in group 4 than in the control groups). A small number of non-proliferating donor fibroblasts was observed in the wound area 3 days after the end of treatment. The cell product is an effective agent for promoting wound healing during the regenerative phase. The experiments demonstrated that a gel populated by dermal fibroblasts can stimulate reparative regeneration processes in deep partial- and full-thickness burn wounds.

摘要

本研究的目的是评估一种基于成纤维细胞的含细胞伤口敷料在羟乙基纤维素(HEC)凝胶中对动物模型中深度部分厚度和/或全层皮肤烧伤进行局部治疗的疗效。将大鼠(雄性Wistar,n = 100)进行全层热烧伤(16 cm)。烧伤后一天进行彻底的坏死组织切除术。三天后,将大鼠随机分为四组之一:第1组(不治疗),第2组(氯霉素和甲基尿嘧啶软膏,一种常规临床治疗),第3组(无细胞凝胶,模拟治疗)和第4组(真皮成纤维细胞浸渍的HEC凝胶)。治疗持续五天。通过平面测量、细胞学、组织学和免疫组织化学方法评估伤口愈合过程。确定了伤口愈合速率和伤口细胞学特征的差异。在第4组中,显示出一种再生型细胞图谱,其特征是与未治疗和模拟治疗动物的样本相比,成纤维细胞数量显著增加。第4组动物烧伤伤口的活检样本显示存在成熟的肉芽组织和大量微血管。修复过程受到刺激,伤口区域新形成的肉芽组织和表皮厚度增加、细胞增多以及再上皮化活性增强证明了这一点。第4组中Ki-67阳性增殖细胞的数量明显高于对照组。治疗结束后3天,在伤口区域观察到少量非增殖性供体成纤维细胞。该细胞产物是促进再生期伤口愈合的有效药物。实验表明,由真皮成纤维细胞填充的凝胶可以刺激深度部分厚度和全层烧伤伤口的修复再生过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/924f/11505042/2059d76c6131/biomedicines-12-02215-g001.jpg

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