Jeong Seol-Ha, Shin Da-Yong, Kang In-Ku, Song Eun-Ho, Seong Yun-Jeong, Park Ji-Ung, Kim Hyoun-Ee
Department of Materials Science and Engineering, Seoul National University, Seoul 08826, South Korea.
Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul 07061, South Korea.
ACS Biomater Sci Eng. 2018 Jul 9;4(7):2380-2389. doi: 10.1021/acsbiomaterials.8b00198. Epub 2018 May 22.
In this study, we report the development of a hyaluronic acid (HA)-based composite hydrogel containing calcium fluoride (CaF) with good biocompatibility and antibacterial properties for multifunctional wound dressing applications. CaF was newly selected for incorporation within HA because it can release both Ca and F ions, which are well-known ions for affecting cell proliferation and inhibiting bacterial growth, respectively. In particular, an in situ precipitation process enables easy control over the released amount of F ions by simply adjusting the precursor solutions (calcium chloride (CaCl) and ammonium fluoride (NHF)) used for the CaF precipitation. CaF particles were uniformly embedded within a HA-based pure hydrogel using an in situ precipitation process. Through variation of the CaCl and NHF concentrations used in the precipitation as well as the precipitation time, composite hydrogels with different ion-release profiles were obtained. By controlling the precipitation time, especially for 10 min and after 30 min, large differences in the ion-release profiles as a function of CaF concentration were observed. A shorter precipitation time resulted in faster release of fluoride, whereas for the 30 min and 1 h samples, sustained ion release was achieved. Colony tests and live/dead assays using and revealed a lower density of bacteria on the CaF composite hydrogels than on the pure hydrogel for both strains. In addition, improved cellular responses such as cell attachment and proliferation were also observed for the CaF composite hydrogels compared to those for the pure hydrogel. Furthermore, the composite hydrogels exhibited excellent wound healing efficiency, as evidenced by an in vitro cell migration assay. Finally, monitoring of the wound closure changes using a full-thickness wound in a rat model revealed the accelerated wound healing capability of the CaF composite hydrogels compared with that of the pure hydrogel. Based on our findings, these CaF composite hydrogels show great potential for application as advanced hydrogel wound dressings with antibacterial properties and accelerated wound-healing capabilities.
在本研究中，我们报道了一种基于透明质酸（HA）的复合水凝胶的开发，该水凝胶含有氟化钙（CaF），具有良好的生物相容性和抗菌性能，可用于多功能伤口敷料应用。新选择将CaF掺入HA中，因为它可以释放Ca和F离子，分别是影响细胞增殖和抑制细菌生长的著名离子。特别是，原位沉淀过程通过简单地调整用于CaF沉淀的前体溶液（氯化钙（CaCl）和氟化铵（NHF）），能够轻松控制F离子的释放量。使用原位沉淀过程将CaF颗粒均匀地嵌入基于HA的纯水凝胶中。通过改变沉淀中使用的CaCl和NHF浓度以及沉淀时间，获得了具有不同离子释放曲线的复合水凝胶。通过控制沉淀时间，特别是10分钟和30分钟后，观察到离子释放曲线随CaF浓度的变化存在很大差异。较短的沉淀时间导致氟化物释放更快，而对于30分钟和1小时的样品，则实现了持续的离子释放。使用两种菌株进行的菌落测试和活/死分析表明，CaF复合水凝胶上的细菌密度低于纯水凝胶。此外，与纯水凝胶相比，CaF复合水凝胶还观察到了改善的细胞反应，如细胞附着和增殖。此外，复合水凝胶表现出优异的伤口愈合效率，体外细胞迁移试验证明了这一点。最后，使用大鼠模型中的全层伤口监测伤口闭合变化，结果显示CaF复合水凝胶与纯水凝胶相比具有加速伤口愈合的能力。基于我们的研究结果，这些CaF复合水凝胶作为具有抗菌性能和加速伤口愈合能力的先进水凝胶伤口敷料具有巨大的应用潜力。
