College of Food Science and Technology, Yunnan Agricultural University, No. 452 Fengyuan Road, Kunming 650000, China; Yunnan Provincial Key Laboratory of Precision Nutrition and Personalized Food Manufacturing, Yunnan Agricultural University, Kunming 650000, China.
Department of Cardiovascular Surgery, The First People's Hospital of Yunnan Province, Xishan District, No.157 Jinbi Road, Kunming 650032, China; School of Medical, Kunming University of Science and Technology, No.727 Jingming South Road, Kunming 650000, China.
Int J Biol Macromol. 2024 Jun;269(Pt 2):132140. doi: 10.1016/j.ijbiomac.2024.132140. Epub 2024 May 7.
Wounding is one of the most common healthcare problems. Bioactive hydrogels have attracted much attention in first-aid hemostasis and wound healing due to their excellent biocompatibility, antibacterial properties, and pro-healing bioactivity. However, their applications are limited by inadequate mechanical properties. In this study, we first prepared edible rose-derived exosome-like nanoparticles (ELNs) and used them to encapsulate antimicrobial peptides (AMP), abbreviated as ELNs(AMP). ELNs(AMP) showed superior intracellular antibacterial activity, 2.5 times greater than AMP, in in vitro cell infection assays. We then prepared and tested an FDA-approved fibrin-gel of fibrinogen and thrombin encapsulating ELNs(AMP) and novobiocin sodium salt (NB) (ELNs(AMP)/NB-fibrin-gels). The fibrin gel showed a sustained release of ELNs(AMP) and NB over the eight days of testing. After spraying onto the skin, the formulation underwent in situ gelation and developed a stable patch with excellent hemostatic performance in a mouse liver injury model with hemostasis in 31 s, only 35.6 % of the PBS group. The fibrin gel exhibited pro-wound healing properties in the mouse-infected skin defect model. The thickness of granulation tissue and collagen of the ELNs(AMP)/NB-fibrin-gels group was 4.00, 6.32 times greater than that of the PBS group. In addition, the ELNs(AMP)/NB-fibrin-gels reduced inflammation (decreased mRNA levels of TNF-α, IL-1β, IL6, MCP1, and CXCL1) at the wound sites and demonstrated a biocompatible and biosafe profile. Thus, we have developed a hydrogel system with excellent hemostatic, antibacterial, and pro-wound healing properties, which may be a candidate for next-generation tissue regeneration with a wide clinical application for first-aid hemostasis and infected wound healing.
创伤是最常见的医疗保健问题之一。由于其出色的生物相容性、抗菌性能和促进愈合的生物活性，生物活性水凝胶在急救止血和伤口愈合方面引起了广泛关注。然而，它们的应用受到机械性能不足的限制。在本研究中，我们首先制备了可食用的玫瑰衍生的外泌体样纳米颗粒（ELNs），并将其用于封装抗菌肽（AMP），缩写为 ELNs(AMP)。ELNs(AMP)在体外细胞感染实验中表现出比 AMP 高 2.5 倍的卓越细胞内抗菌活性。然后，我们制备并测试了一种 FDA 批准的纤维蛋白原和凝血酶包封 ELNs(AMP)和新生霉素钠盐（NB）的纤维蛋白凝胶（ELNs(AMP)/NB-纤维蛋白凝胶）。该纤维蛋白凝胶在 8 天的测试中显示出 ELNs(AMP)和 NB 的持续释放。在喷涂到皮肤上后，该制剂在原位凝胶化并形成稳定的贴片，在止血时间为 31 秒的小鼠肝损伤模型中表现出出色的止血性能，仅为 PBS 组的 35.6%。纤维蛋白凝胶在感染皮肤缺陷模型中的小鼠伤口愈合中表现出促伤口愈合的特性。ELNs(AMP)/NB-纤维蛋白凝胶组的肉芽组织和胶原蛋白厚度分别是 PBS 组的 4.00、6.32 倍。此外，ELNs(AMP)/NB-纤维蛋白凝胶减少了伤口部位的炎症（降低 TNF-α、IL-1β、IL6、MCP1 和 CXCL1 的 mRNA 水平），并表现出生物相容性和生物安全性特征。因此，我们开发了一种具有出色止血、抗菌和促伤口愈合性能的水凝胶系统，它可能成为下一代组织再生的候选者，具有广泛的急救止血和感染性伤口愈合的临床应用。
