Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Key Laboratory of Regenerative Medicine of Ministry of Education, Guangdong Provincial Engineering and Technological Research Centre for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
Department of Ophthalmology, General Hospital of Southern Theater Command, PLA, Guangzhou 510010, China.
Acta Biomater. 2024 Nov;189:270-285. doi: 10.1016/j.actbio.2024.09.045. Epub 2024 Oct 1.
Diabetic ulcers are one of the common complications in diabetic patients. Delayed wound healing is associated with persistent pro-inflammatory M1 polarization, reduced angiogenesis and increased reactive oxygen species (ROS) in the microenvironment. Wound healing consists of multiple phases and therefore requires treatment tailored to each phase. In this study, a biphasic drug-releasing microneedle (MN) was fabricated to achieve early ROS scavenging and late accelerated angiogenesis to promote wound healing. Vascular endothelial growth factor (VEGF) was first encapsulated in methacryloylated sulfonated chitosan (SCSMA) microspheres (V@MP), and then V@MP was loaded into hyaluronic acid (HA) microneedles along with cerium dioxide nanoparticles (CONPs). Rapid dissolution of HA rapidly releases the CONPs to clear ROS, whereas the V@MP stays in the wound. SCSMA slow degradation prolongs the release of VEGF, thereby promoting angiogenesis. In vitro and in vivo studies have shown that this biphasic drug-releasing smart microneedle improves cell proliferation and migration, effectively scavenges ROS, promotes angiogenesis and tissue regeneration, and synergistically promotes M2 macrophage polarization. It provides a new delivery mode for nano-enzymes and growth factors that could be multifunctional and synergistic in the treatment of diabetic ulcers. STATEMENT OF SIGNIFICANCE: In our study, we present a microneedle (V@MP/C@MN) that can release drugs biphasically, which showed good repair ability in diabetic ulcer model. Large amounts of CONPs were rapidly released to alleviate oxidative stress during the inflammation of the wound, and V@MP stayed in the wound for a long period of time to release VEGF and promote angiogenesis in the late stage of wound healing. The results indicated that V@MP/C@MN could promote cell proliferation and migration, effectively scavenge ROS, promote angiogenesis and tissue regeneration, and synergistically promote M2 macrophage polarization, which could play a multifunctional and synergistic role in the treatment of diabetic ulcers.
糖尿病溃疡是糖尿病患者常见的并发症之一。伤口愈合延迟与持续的促炎 M1 极化、血管生成减少和微环境中活性氧（ROS）增加有关。伤口愈合由多个阶段组成，因此需要针对每个阶段进行治疗。在这项研究中，制备了一种双相药物释放微针（MN），以实现早期 ROS 清除和晚期加速血管生成，从而促进伤口愈合。首先将血管内皮生长因子（VEGF）包封在甲基丙烯酰化磺化壳聚糖（SCSMA）微球（V@MP）中，然后将 V@MP 与二氧化铈纳米颗粒（CONPs）一起装载到透明质酸（HA）微针中。HA 的快速溶解迅速释放 CONPs 以清除 ROS，而 V@MP 留在伤口中。SCSMA 的缓慢降解延长了 VEGF 的释放，从而促进了血管生成。体外和体内研究表明，这种双相药物释放智能微针可提高细胞增殖和迁移能力，有效清除 ROS，促进血管生成和组织再生，并协同促进 M2 巨噬细胞极化。它为纳米酶和生长因子提供了一种新的输送模式，可在治疗糖尿病溃疡方面具有多功能和协同作用。
在我们的研究中，我们提出了一种可以双相释放药物的微针（V@MP/C@MN），它在糖尿病溃疡模型中表现出良好的修复能力。大量 CONPs 迅速释放，以缓解伤口炎症期间的氧化应激，而 V@MP 长时间留在伤口中，以在伤口愈合的后期释放 VEGF 并促进血管生成。结果表明，V@MP/C@MN 可促进细胞增殖和迁移，有效清除 ROS，促进血管生成和组织再生，并协同促进 M2 巨噬细胞极化，可在治疗糖尿病溃疡方面发挥多功能和协同作用。
