Zhang Yu, Cai Renzhong, Li Jun, Wu Xu
Department of Thoracic and Cardiovascular Surgery/Huiqiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Department of Breast Surgery, Hainan General Hospital, Hainan Hospital Affiliated to Hainan Medical College, Haikou 570311, China.
Membranes (Basel). 2023 Mar 14;13(3):335. doi: 10.3390/membranes13030335.
Inflammatory cells mount an immune response against in vitro engineered cartilage implanted into immunocompetent animals, consequently limiting the usage of tissue-engineered cartilage to repair cartilage defects. In this study, curcumin (Cur)-an anti-inflammatory agent-was mixed with poly(lactic-co-glycolic acid) (PLGA) to develop a Cur/PLGA nanofibrous membrane with nanoscale pore size and anti-inflammatory properties. Fourier-transform infrared spectroscopy and high-performance liquid chromatography analyses confirmed the successful loading of Cur into the Cur/PLGA nanofibrous membrane. The results of the in vitro assay demonstrated the sustained release kinetics and enhanced stability of Cur in the Cur/PLGA nanofibrous membrane. Western blotting and enzyme-linked immunosorbent assay analyses revealed that the Cur/PLGA nanofibrous membrane significantly downregulated the expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α). A chondrocyte suspension was seeded into a porous PLGA scaffold, and the loaded scaffold was cultured for 3 weeks in vitro to engineer cartilage tissues. The cartilage was packed with the in vitro engineered Cur/PLGA nanofibrous membrane and subcutaneously implanted into rats to generate an immunosuppressive niche. Compared with those in the PLGA-implanted and pure cartilage (without nanofibrous membrane package)-implanted groups, the cartilage was well preserved and the inflammatory response was suppressed in the Cur/PLGA-implanted group at weeks 2 and 4 post-implantation. Thus, this study demonstrated that packaging the cartilage with the Cur/PLGA nanofibrous membrane effectively generated an immunosuppressive niche to protect the cartilage against inflammatory invasion. These findings enable the clinical translation of tissue-engineered cartilage to repair cartilage defects.
炎症细胞会对植入具有免疫活性动物体内的体外工程化软骨发起免疫反应，从而限制了组织工程化软骨用于修复软骨缺损的应用。在本研究中，将姜黄素（Cur）——一种抗炎剂——与聚乳酸-乙醇酸共聚物（PLGA）混合，以制备具有纳米级孔径和抗炎特性的Cur/PLGA纳米纤维膜。傅里叶变换红外光谱和高效液相色谱分析证实Cur成功负载到Cur/PLGA纳米纤维膜中。体外测定结果表明Cur在Cur/PLGA纳米纤维膜中具有缓释动力学和增强的稳定性。蛋白质印迹和酶联免疫吸附测定分析显示，Cur/PLGA纳米纤维膜显著下调炎症细胞因子（IL-1β、IL-6和TNF-α）的表达。将软骨细胞悬液接种到多孔PLGA支架中，将负载后的支架在体外培养3周以构建软骨组织。将构建的软骨用体外工程化的Cur/PLGA纳米纤维膜包裹，并皮下植入大鼠体内以形成免疫抑制微环境。与PLGA植入组和纯软骨（无纳米纤维膜包裹）植入组相比，在植入后第2周和第4周，Cur/PLGA植入组的软骨保存良好，炎症反应受到抑制。因此，本研究表明用Cur/PLGA纳米纤维膜包裹软骨可有效形成免疫抑制微环境，保护软骨免受炎症侵袭。这些发现使得组织工程化软骨修复软骨缺损能够进行临床转化。
