Department of General Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Huangpu, Shanghai, China.
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Huangpu, Shanghai, China.
Int J Nanomedicine. 2020 Jan 20;15:333-346. doi: 10.2147/IJN.S225197. eCollection 2020.
Wound healing, especially of extensive full-thickness wounds, is one of the most difficult problems in clinical studies. In this study, we prepared a novel substance P (SP)-delivery system using zeolite imidazolate framework-8 (ZIF-8) nanoparticles.
We synthesized ZIF-8 nanoparticles using a modified biomimetic mineralization method. We then coated SP-loaded ZIF-8 nanoparticles (SP@ZIF-8) with polyethylene glycol-thioketal (PEG-TK) to fabricate SP@ZIF-8-PEG-TK nanoparticles, and encapsulated them in injectable hydrogel composed of sodium alginate and pectin and cross-linked using calcium chloride. The final hydrogel wound dressing containing SP@ZIF-8-PEG-TK nanoparticles was called SP@ZIF-8-PEG-TK@CA.
The fabricated ZIF-8 nanoparticles had high SP-loading efficiency. SP-release assay showed that the SP@ZIF-8-PEG-TK nanoparticles maintained drug activity and showed responsive release under stimulation by reactive oxygen species. The SP@ZIF-8-PEG-TK nanoparticles promoted proliferation of human dermal fibroblasts, up-regulated expression levels of inflammation-related genes in macrophages, and exhibited favorable cytocompatibility in vitro. Full-thickness excision wound models in vivo confirmed that SP@ZIF-8-PEG-TK@CA dressings had excellent wound-healing efficacy by promoting an early inflammatory response and subsequent M2 macrophage polarization in the wound-healing process.
In conclusion, these findings indicated that SP@ZIF-8-PEG-TK@CA dressings might be useful for wound dressing applications in the clinic.
创伤愈合，尤其是广泛的全层伤口的愈合，是临床研究中最困难的问题之一。在本研究中，我们使用沸石咪唑酯骨架-8（ZIF-8）纳米粒子制备了一种新型的神经肽（SP）递药系统。
我们使用改良的仿生矿化方法合成了 ZIF-8 纳米粒子。然后，我们将载有 SP 的 ZIF-8 纳米粒子（SP@ZIF-8）用聚乙二醇硫代缩酮（PEG-TK）包被，制备出 SP@ZIF-8-PEG-TK 纳米粒子，并将其包裹在由海藻酸钠和果胶组成的可注射水凝胶中，再用氯化钙交联。最终的含有 SP@ZIF-8-PEG-TK 纳米粒子的水凝胶伤口敷料被称为 SP@ZIF-8-PEG-TK@CA。
所制备的 ZIF-8 纳米粒子具有较高的 SP 载药效率。SP 释放实验表明，SP@ZIF-8-PEG-TK 纳米粒子在活性氧刺激下保持药物活性并呈现响应性释放。SP@ZIF-8-PEG-TK 纳米粒子促进了人真皮成纤维细胞的增殖，上调了巨噬细胞中炎症相关基因的表达水平，并且在体外具有良好的细胞相容性。体内全层切除伤口模型证实，SP@ZIF-8-PEG-TK@CA 敷料通过促进伤口愈合过程中的早期炎症反应和随后的 M2 巨噬细胞极化，具有优异的伤口愈合效果。
总之，这些发现表明 SP@ZIF-8-PEG-TK@CA 敷料可能在临床伤口敷料应用中具有应用前景。
