Pilloni Andrea, Marini Lorenzo, Gagliano Nicoletta, Canciani Elena, Dellavia Claudia, Cornaghi Laura Brigida, Costa Ezio, Rojas Mariana A
Section of Periodontics, Department of Oral and Maxillofacial Sciences, Sapienza University of Rome, Rome, Italy.
Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy.
J Periodontol. 2023 Jul;94(7):868-881. doi: 10.1002/JPER.22-0338. Epub 2023 Feb 9.
Hyaluronic acid (HA) exerts a fundamental role in tissue repair. In vitro and animal studies demonstrated its ability to enhance wound healing. Nevertheless, in vivo human studies evaluating mechanisms involved in oral soft tissue repair are lacking. The aim of this study was to evaluate the in vivo effect of HA on early wound healing of human gingival (G) tissues.
In the present randomized, split-mouth, double-blind, clinical trial, G biopsies were obtained in eight patients 24 h post-surgery after HA application (HA group) and compared with those obtained from the same patients without HA application (no treatment; NT group). Clinical response was evaluated through the Early Wound Healing Score (EHS). Microvascular density (MVD), collagen content and cellular proliferation were evaluated through sirius red and Masson trichrome staining, and Ki-67 immunohistochemistry, respectively. To assess collagen turnover, MMP-1, MMP-2, MMP-9, TGF-β1 protein levels and LOX, MMP1, TIMP1, TGFB1 gene expression were analyzed by western blot and real time polymerase chain reaction.
Twenty-four hours after surgery, the EHS was significantly higher in the HA group. MVD, collagen content, and cell proliferation were not affected. LOX mRNA, MMP-1 protein, and TIMP1 gene expression were significantly upregulated in the HA compared to the NT group.
The additional use of 0.8% HA gel does not modify new blood vessel growth in the early phase of gingival wound healing. Concerning the secondary outcomes, HA seems to enhance extracellular matrix remodeling and collagen maturation, which could drive early wound healing of G tissues to improve clinical parameters.
透明质酸（HA）在组织修复中发挥着重要作用。体外和动物研究表明其具有促进伤口愈合的能力。然而，缺乏评估参与口腔软组织修复机制的人体体内研究。本研究的目的是评估HA对人牙龈（G）组织早期伤口愈合的体内作用。
在本项随机、双侧、双盲临床试验中，8例患者在应用HA后24小时进行G组织活检（HA组），并与未应用HA的同一患者的活检组织（未治疗；NT组）进行比较。通过早期伤口愈合评分（EHS）评估临床反应。分别通过天狼星红和Masson三色染色以及Ki-67免疫组织化学评估微血管密度（MVD）、胶原蛋白含量和细胞增殖。为了评估胶原蛋白周转，通过蛋白质免疫印迹法和实时聚合酶链反应分析MMP-1、MMP-2、MMP-9、TGF-β1蛋白水平以及LOX、MMP1、TIMP1、TGFB1基因表达。
术后24小时，HA组的EHS显著更高。MVD、胶原蛋白含量和细胞增殖未受影响。与NT组相比，HA组中LOX mRNA、MMP-1蛋白和TIMP1基因表达显著上调。
额外使用0.8% HA凝胶不会改变牙龈伤口愈合早期的新血管生长。关于次要结果，HA似乎可促进细胞外基质重塑和胶原蛋白成熟，这可能推动G组织的早期伤口愈合以改善临床参数。
