Abdelkhalek Mohamed A, Abdelaal Mohamed M, Abdel Gaber Sara A
Institute of Nanoscience and Nanotechnology, Kafrelsheikh University, 33516 Kafrelsheikh, Egypt.
Cardiothoracic Surgery Department, Medicine Faculty, Kafrelsheikh University, 33516 Kafrelsheikh, Egypt.
Int J Pharm. 2025 Oct 15;683:126023. doi: 10.1016/j.ijpharm.2025.126023. Epub 2025 Aug 5.
Diabetic foot ulcers (DFUs) pose a major clinical burden due to chronic infection and impaired tissue regeneration. This study presents a dual-stage therapeutic strategy to promote the healing of infected diabetic wounds. In the first stage, cold atmospheric plasma was applied for 20 s which exerted a potent antibacterial effect against Staphylococcus aureus and Pseudomonas aeruginosa. The second stage involved in situ electrospinning of arginine-loaded mesoporous silica nanoparticles (Arg@MSN) embedded within polycaprolactone (PCL) nanofibers (Arg@NFs) using a portable, pen-like electrospinning device. MSN were spherical with an average diameter of 85 ± 10 nm and 80 % arginine loading was achieved. The nanofibers were randomly oriented with a fiber diameter ranging between 100 and 140 nm. Arg@NFs demonstrated 87 ± 5 % arginine release over seven days. In vivo studies showed that plasma-treated wounds exhibited a 2.85-fold increase in wound closure compared to the Arg@NFs group by day 14, while the combination therapy led to a complete wound healing. Histological and Masson's trichrome staining revealed full epithelialization and dense collagen deposition in the dual treatment group. Compared to monotherapies, the dual therapy group showed a significantly higher expression of VEGF, FGF, and PDGF and a significant downregulation of NF-κB and COX-2. These findings highlight that combining non-thermal plasma with arginine-releasing nanofibers is a promising therapeutic strategy for enhancing infected diabetic wound healing.
糖尿病足溃疡（DFUs）由于慢性感染和组织再生受损而带来重大临床负担。本研究提出了一种双阶段治疗策略来促进感染性糖尿病伤口的愈合。在第一阶段，应用冷大气等离子体20秒，其对金黄色葡萄球菌和铜绿假单胞菌具有强大的抗菌作用。第二阶段涉及使用便携式笔状静电纺丝装置将负载精氨酸的介孔二氧化硅纳米颗粒（Arg@MSN）原位静电纺丝到聚己内酯（PCL）纳米纤维（Arg@NFs）中。MSN呈球形，平均直径为85±10nm，精氨酸负载量达到80%。纳米纤维随机取向，纤维直径在100至140nm之间。Arg@NFs在七天内精氨酸释放率为87±5%。体内研究表明，到第14天时，与Arg@NFs组相比，经等离子体处理的伤口愈合率提高了2.85倍，而联合治疗导致伤口完全愈合。组织学和Masson三色染色显示双治疗组完全上皮化且胶原沉积致密。与单一疗法相比，联合治疗组VEGF、FGF和PDGF的表达显著更高，NF-κB和COX-2显著下调。这些发现突出表明，将非热等离子体与释放精氨酸的纳米纤维相结合是增强感染性糖尿病伤口愈合的一种有前景的治疗策略。
