Cai Xiang, Zhu Jiawen, Luo Xin, Jin Guoguo, Huang Yadong, Li Lihua
State Key Laboratory of Bioactive Molecules and Drug Gability Assessment, Jinan University, Guangzhou 510632, China.
Institute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou 510632, China.
Bioengineering (Basel). 2023 Dec 29;11(1):38. doi: 10.3390/bioengineering11010038.
Approximately 59.4-100% of head and neck cancer patients receiving radiotherapy or radio chemotherapy suffer from aphthous ulcers (AUs), which seriously affect the subsequent treatment. At the same time, AUs are a common oral mucosal disease with a high incidence rate among the population, often accompanied by severe pain, and affect both physical and mental health. Strategies to increase the ulcer healing rate and relieve pain symptoms quickly is a long-term clinical objective. Oral mucosal discontinuity is the main histological hallmark of AUs. So, covering the inner mucosal defect with an in vitro engineered oral mucosal equivalent shows good prospects for AU alleviation. Fibronectin (FN) is a glycopeptide in the extracellular matrix and exhibits opsonic properties, aiding the phagocytosis and clearance of foreign pathogens through all stages of ulcer healing. But native FN comes from animal blood, which has potential health risks. rhFN3C was designed with multi-domains of native FN, whose core functions are the recruitment of cells and growth factors to accelerate AU healing. rhFN3C is a peptide-fused recombinant protein. The peptides are derived from the positions of 1444-1545 (FNIII10) and 1632-1901 (FNIII12-14) in human native FN. We optimized the fermentation conditions of rhFN3C in BL21 to enable high expression levels. rhFN3C is thermally stable and nontoxic for L929, strongly promotes the migration and adhesion of HaCaT, decreases the incidence of wound infection, and shortens the mean healing time by about 2 days compared to others ( < 0.01). rhFN3C may have great potential for use in the treatment of AUs. The specific methods and mechanisms of rhFN3C are yet to be investigated.
接受放疗或放化疗的头颈癌患者中,约59.4%-100%会患口疮性溃疡(AUs),这严重影响后续治疗。同时,AUs是一种常见的口腔黏膜疾病,在人群中发病率很高,常伴有剧痛,影响身心健康。提高溃疡愈合率并快速缓解疼痛症状的策略是长期的临床目标。口腔黏膜连续性中断是AUs的主要组织学特征。因此,用体外构建的口腔黏膜替代物覆盖黏膜内缺损对缓解AUs显示出良好前景。纤连蛋白(FN)是细胞外基质中的一种糖肽,具有调理特性,在溃疡愈合的各个阶段有助于吞噬和清除外来病原体。但天然FN来自动物血液,存在潜在健康风险。重组人纤连蛋白3C(rhFN3C)是根据天然FN的多个结构域设计的,其核心功能是募集细胞和生长因子以加速AUs愈合。rhFN3C是一种肽融合重组蛋白。这些肽来源于人天然FN中1444-1545位(FNIII10)和1632-1901位(FNIII12-14)。我们优化了rhFN3C在BL21中的发酵条件以实现高表达水平。rhFN3C热稳定,对L929无毒,强烈促进HaCaT细胞的迁移和黏附,降低伤口感染发生率,与其他物质相比平均愈合时间缩短约2天(<0.01)。rhFN3C在治疗AUs方面可能具有巨大潜力。rhFN3C的具体作用方法和机制还有待研究。