Kurenkova Anastasiia D, Serejnikova Natalia B, Sheleg Sofia A, Fayzullin Alexey L, Denisov Nikolai E, Igrunkova Alexandra V, Sadchikova Elena R, Antoshin Artem A, Timashev Peter S
Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya St., 119991 Moscow, Russia.
Department of Human Anatomy and Histology, N.V. Sklifosovsky Institute of Clinical Medicine, Sechenov First Moscow State Medical University (Sechenov University), 11, Building 10, Mokhovaya St., 125009 Moscow, Russia.
Int J Mol Sci. 2025 Feb 24;26(5):1956. doi: 10.3390/ijms26051956.
Ear reconstruction surgeries for congenital deformities and trauma are common, highlighting the need for improved cartilage regeneration. Lactoferrin (LF), a natural and cost-effective protein, is promising due to its anti-inflammatory, antimicrobial, and prochondrogenic properties. This study investigates the effects of LF on the viability, proliferation, and chondrogenesis of rabbit auricular chondrocytes. For in vitro studies, auricular chondrocytes were cultured for three passages, after which 3D pellets were formed. LF significantly increased chondrocyte metabolic activity by 1.5 times at doses of 10 and 500 μg/mL. At passage 3, LF at concentrations of 10 and 100 μg/mL increased cell proliferation rates by 2- and 1.5-fold, respectively. Immunohistochemical staining of the pellets demonstrated that LF at 10 μg/mL increased the amount of sex-determining region Y-Box Transcription Factor 9 (Sox9)+ cells by 30%, while at 100 μg/mL, it doubled the type II collagen deposits. For in vivo studies, a rabbit ear defect model was utilized. On post-operative day 60, the LF-treated group exhibited more mature cartilage regeneration, with a higher density of elastic fibers. By day 90 post-surgery, LF application led to the restoration of normal elastic cartilage throughout the defect. These findings suggest that LF promotes auricular chondrocytes chondrogenesis and could be beneficial for tissue engineering of the elastic cartilage.
用于先天性畸形和创伤的耳部重建手术很常见，这凸显了改善软骨再生的必要性。乳铁蛋白（LF）是一种天然且经济高效的蛋白质，因其具有抗炎、抗菌和促软骨生成特性而颇具前景。本研究调查了LF对兔耳软骨细胞活力、增殖和软骨形成的影响。在体外研究中，耳软骨细胞培养三代后形成三维微球。在10和500μg/mL剂量下，LF可使软骨细胞代谢活性显著提高1.5倍。在第3代时，10和100μg/mL浓度的LF分别使细胞增殖率提高了2倍和1.5倍。微球的免疫组织化学染色显示，10μg/mL的LF使性别决定区Y盒转录因子9（Sox9）+细胞数量增加了30%，而在100μg/mL时，II型胶原沉积量增加了一倍。在体内研究中，使用了兔耳缺损模型。术后第60天，LF治疗组显示出更成熟的软骨再生，弹性纤维密度更高。到术后第90天，应用LF导致整个缺损处恢复了正常的弹性软骨。这些发现表明，LF促进耳软骨细胞软骨形成，可能对弹性软骨组织工程有益。
