Department of ORL-HNS, Shanghai East Hospital, Shanghai, China.
School of Medicine, Tongji University, Shanghai, China.
FASEB J. 2021 May;35(5):e21442. doi: 10.1096/fj.202002611R.
Cold atmospheric plasma (CAP) is an emerging technology for biomedical applications, exemplified by its antimicrobial and antineoplastic potentials. On the contrary, acidic fibroblast growth factor (aFGF) has been a long-standing potent mitogen for cells from various origins. In this study, we are the first to develop a multimodal treatment combining the aforementioned physicochemical and pharmacological treatments and investigated their individual and combined effects on wound healing, angiogenesis, neurogenesis, and osteogenesis. This work was performed at the tissue, cellular, protein, and gene levels, using histochemical staining, flow cytometry, ELISA, and PCR, respectively. Depending on the type of target tissue, various combinations of aforementioned methods were used. The results showed that the enhancement on would healing and angiogenesis by CAP and aFGF were synergistic. The former was manifested by increased murine fibroblast proliferation and reduced cutaneous tissue inflammation, whereas the latter by upregulated proangiogenic markers in vivo, for example, CD31, VEGF, and TGF-β, and downregulated antiangiogenic proteins in vitro, for example, angiostatin and angiopoietin-2, respectively. In addition, aFGF outperformed CAP during neurogenesis, which was evidenced by superior neurite outgrowth, while CAP exceeded aFGF in osteogenesis which was demonstrated by more substantial bone nodule formation. These novel findings not only support the fact that CAP and aFGF are both multipotent agents during tissue regeneration, but also highlight the potential of our multimodal treatment combining the individual advantages of CAP and aFGF. The versatile administration route, that is, topical and/or systemic, might further broaden its applications.
冷等离体等离子体（CAP）是一种新兴的生物医学应用技术，其具有抗菌和抗肿瘤潜能就是很好的例证。相反，酸性成纤维细胞生长因子（aFGF）一直以来都是各种来源细胞的强有力有丝分裂原。在这项研究中，我们首次开发了一种将上述物理化学和药理学治疗相结合的多模态治疗方法，并研究了它们对伤口愈合、血管生成、神经发生和骨生成的单独和联合作用。这项工作分别在组织、细胞、蛋白质和基因水平上使用组织化学染色、流式细胞术、ELISA 和 PCR 进行。根据靶组织的类型，使用了上述方法的各种组合。结果表明，CAP 和 aFGF 对伤口愈合和血管生成的增强具有协同作用。前者表现为增加了小鼠成纤维细胞的增殖和减少了皮肤组织的炎症，而后者则通过体内上调了促血管生成标记物，例如 CD31、VEGF 和 TGF-β，以及体外下调了抗血管生成蛋白，例如血管抑素和血管生成素-2。此外，在神经发生方面，aFGF 优于 CAP，表现为更好的神经突生长，而在骨生成方面，CAP 优于 aFGF，表现为更多的骨结节形成。这些新发现不仅支持 CAP 和 aFGF 在组织再生过程中都是多能剂的事实，而且还突出了我们的多模态治疗方法的潜力，该方法结合了 CAP 和 aFGF 的各自优势。多用途的给药途径，即局部和/或全身给药，可能会进一步拓宽其应用范围。
