Ma Shufang, Feng Xinxing, Liu Fangxiu, Wang Bin, Zhang Hua, Niu Xufeng
Department of Rheumatology The Fourth Central Hospital of Baoding City Baoding P. R. China.
Endocrinology and Cardiovascular Disease Centre Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing P. R. China.
Eng Life Sci. 2021 May 12;21(10):709-720. doi: 10.1002/elsc.202100040. eCollection 2021 Oct.
Poly(lactide-co-glycolide) (PLGA) shows great potentials in biomedical applications, in particular with the field of biodegradable implants and control release technologies. However, there are few systematic and detailed studies on the influence of PLGA degradation behavior on the immunogenicity. In this study, in order to develop a method for dynamically assessing the immunological response of PLGA throughout the implantation process, PLGA particles are fabricated using an o/w single-emulsion method. The physicochemical characterizations of the prepared PLGA particles during in vitro hydrolytic degradation are investigated. Then, a series of immunological effects triggered by PLGA by-products formed with degradation process are evaluated, including cell viability, apoptosis, polarization and inflammatory reaction. THP-1 human cell line is set as in vitro cell model. Our results show that PLGA degradation-induced acid environment decreases cell viability and increases cell apoptosis, which is a potential factor affecting cell function. In particular, the macrophages exhibit up-regulations in both M1 subtype related surface markers and pro-inflammatory cytokines with the degradation process of PLGA, which indicates the degradation products of PLGA can convert macrophages to the pro-inflammatory (M1) polarization state. All these findings provide the mechanism of PLGA-induced inflammation and lay the foundation for the design of next-generation PLGA-based biomaterials endowed with immunomodulatory functions.
聚（丙交酯-乙交酯）（PLGA）在生物医学应用中显示出巨大潜力，尤其是在可生物降解植入物和控释技术领域。然而，关于PLGA降解行为对免疫原性的影响，很少有系统而详细的研究。在本研究中，为了开发一种在整个植入过程中动态评估PLGA免疫反应的方法，采用水包油单乳液法制备PLGA颗粒。研究了制备的PLGA颗粒在体外水解降解过程中的物理化学特性。然后，评估了由降解过程中形成的PLGA副产物引发的一系列免疫效应，包括细胞活力、凋亡、极化和炎症反应。将THP-1人细胞系作为体外细胞模型。我们的结果表明，PLGA降解诱导的酸性环境降低了细胞活力并增加了细胞凋亡，这是影响细胞功能的一个潜在因素。特别是，随着PLGA的降解过程，巨噬细胞在M1亚型相关表面标志物和促炎细胞因子方面均表现出上调，这表明PLGA的降解产物可将巨噬细胞转化为促炎（M1）极化状态。所有这些发现提供了PLGA诱导炎症的机制，并为设计具有免疫调节功能的下一代基于PLGA的生物材料奠定了基础。
