Institute for Regenerative Medicine, Sechenov University, 119991 Moscow, Russia.
Central Research Institute of Dentistry and Maxillofacial Surgery, 119991 Moscow, Russia.
Int J Mol Sci. 2024 Sep 17;25(18):10013. doi: 10.3390/ijms251810013.
Currently, an increasing number of patients are undergoing extensive surgeries to restore the mucosa of the gums in the area of recessions. The use of a connective tissue graft from the palate is the gold standard of such surgical treatment, but complications, especially in cases of extensive defects, have led to the development of approaches using xenogeneic collagen matrices and methods to stimulate their regenerative and vasculogenic potential. This study investigated the potential of a xenogeneic scaffold derived from porcine skin Mucoderm and injections of the pCMV-VEGF165 plasmid ('Neovasculgen') to enhance soft gingival tissue volume and vascularization in an experimental model in rabbits. In vitro studies demonstrated the biocompatibility of the matrix and plasmid with gingival mesenchymal stem cells, showing no toxic effects and supporting cell viability and metabolic activity. In the in vivo experiment, the combination of Mucoderm and the pCMV-VEGF165 plasmid (0.12 mg) synergistically promoted tissue proliferation and vascularization. The thickness of soft tissues at the implantation site significantly increased with the combined application (3257.8 ± 1093.5 µm). Meanwhile, in the control group, the thickness of the submucosa was 341.8 ± 65.6 µm, and after the implantation of only Mucoderm, the thickness of the submucosa was 2041.6 ± 496.8 µm. Furthermore, when using a combination of Mucoderm and the pCMV-VEGF165 plasmid, the density and diameter of blood vessels were notably augmented, with a mean value of 226.7 ± 45.9 per 1 mm of tissue, while in the control group, it was only 68.3 ± 17.2 per 1 mm of tissue. With the application of only Mucoderm, it was 131.7 ± 37.1 per 1 mm of tissue, and with only the pCMV-VEGF165 plasmid, it was 145 ± 37.82 per 1 mm of the sample. Thus, the use of the pCMV-VEGF165 plasmid ('Neovasculgen') in combination with the xenogeneic collagen matrix Mucoderm potentiated the pro-proliferative effect of the membrane and the pro-vascularization effect of the plasmid. These results indicate the promising potential of this innovative approach for clinical applications in regenerative medicine and dentistry.
目前，越来越多的患者接受了广泛的手术，以修复牙龈退缩区域的粘膜。使用来自腭部的结缔组织移植物是这种手术治疗的金标准，但并发症，尤其是在广泛缺损的情况下，导致了使用异种胶原基质和刺激其再生和血管生成潜力的方法的发展。本研究调查了源自猪皮 Mucoderm 的异种支架和注射 pCMV-VEGF165 质粒（'Neovasculgen'）在兔实验模型中增强软组织体积和血管化的潜力。体外研究表明，基质和质粒与牙龈间充质干细胞具有生物相容性，没有毒性作用，并支持细胞活力和代谢活性。在体内实验中，Mucoderm 与 pCMV-VEGF165 质粒（0.12mg）联合使用协同促进组织增殖和血管生成。植入部位软组织的厚度随着联合应用显著增加（3257.8 ± 1093.5 µm）。同时，在对照组中，黏膜下组织的厚度为 341.8 ± 65.6 µm，仅植入 Mucoderm 后，黏膜下组织的厚度为 2041.6 ± 496.8 µm。此外，当使用 Mucoderm 和 pCMV-VEGF165 质粒的组合时，血管的密度和直径明显增加，组织中每 1mm 的平均值为 226.7 ± 45.9，而在对照组中，每 1mm 组织中仅为 68.3 ± 17.2。仅应用 Mucoderm 时，每 1mm 组织为 131.7 ± 37.1，仅应用 pCMV-VEGF165 质粒时，每 1mm 样本为 145 ± 37.82。因此，pCMV-VEGF165 质粒（'Neovasculgen'）与异种胶原基质 Mucoderm 的联合应用增强了膜的促增殖作用和质粒的促血管生成作用。这些结果表明，这种创新方法在再生医学和牙科的临床应用中具有广阔的应用前景。
