Department of Chemical Engineering, Wonkwang, University, Iksan, Jeonbuk, 54538, Republic of Korea.
Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Jeonbuk, 54538, Republic of Korea.
Int J Nanomedicine. 2024 Mar 1;19:1683-1697. doi: 10.2147/IJN.S435156. eCollection 2024.
Cartilage regeneration is a challenging issue due to poor regenerative properties of tissues. Electrospun nanofibers hold enormous potentials for treatments of cartilage defects. However, nanofibrous materials used for the treatment of cartilage defects often require physical and/or chemical modifications to promote the adhesion, proliferation, and differentiation of cells. Thus, it is highly desirable to improve their surface properties with functionality. We aim to design hydrophilic, adhesive, and compound K-loaded nanofibers for treatments of cartilage defects.
Hydrophilic and adhesive compound K-containing polycaprolactone nanofibers (CK/PCL NFs) were prepared by coatings of gallic acid-conjugated chitosan (CHI-GA). Therapeutic effects of CHI-GA/CK/PCL NFs were assessed by the expression level of genes involved in the cartilage matrix degradation, inflammatory response, and lipid accumulations in the chondrocytes. In addition, Cartilage damage was evaluated by safranin O staining and immunohistochemistry of interleukin-1β (IL-1β) using OA animal models. To explore the pathway associated with therapeutic effects of CHI-GA/CK/PCL NFs, cell adhesion, phalloidin staining, and the expression level of integrins and peroxisome proliferator-activated receptor (PPARs) were evaluated.
CHI-GA-coated side of the PCL NFs showed hydrophilic and adhesive properties, whereas the unmodified opposite side remained hydrophobic. The expression levels of genes involved in the degradation of the cartilage matrix, inflammation, and lipogenesis were decreased in CHI-GA/CK/PCL NFs owing to the release of CK. In vivo implantation of CHI-GA/CK/PCL NFs into the cartilage reduced cartilage degradation induced by destabilization of the medial meniscus (DMM) surgery. Furthermore, the accumulation of lipid deposition and expression levels of IL-1β was reduced through the upregulation of PPAR.
CHI-GA/CK/PCL NFs were effective in the treatments of cartilage defects by inhibiting the expression levels of genes involved in cartilage degradation, inflammation, and lipogenesis as well as reducing lipid accumulation and the expression level of IL-1β via increasing PPAR.
由于组织再生能力差，软骨再生是一个具有挑战性的问题。静电纺纳米纤维在治疗软骨缺陷方面具有巨大的潜力。然而，用于治疗软骨缺陷的纳米纤维材料通常需要物理和/或化学改性以促进细胞的黏附、增殖和分化。因此，提高其表面性能具有重要意义。我们旨在设计亲水性、黏附性和负载化合物 K 的纳米纤维以治疗软骨缺陷。
通过将没食子酸接枝壳聚糖（CHI-GA）涂覆来制备亲水性、黏附性的含化合物 K 的聚己内酯纳米纤维（CK/PCL NFs）。通过评估与软骨基质降解、炎症反应和软骨细胞脂质积累相关的基因表达水平来评估 CHI-GA/CK/PCL NFs 的治疗效果。此外，通过 safranin O 染色和 OA 动物模型中白细胞介素-1β（IL-1β）的免疫组化评估软骨损伤。为了探索 CHI-GA/CK/PCL NFs 治疗效果相关的途径，评估了细胞黏附、鬼笔环肽染色以及整合素和过氧化物酶体增殖物激活受体（PPARs）的表达水平。
PCL NFs 的 CHI-GA 涂层侧表现出亲水性和黏附性，而未经修饰的相反侧仍保持疏水性。由于 CK 的释放，CHI-GA/CK/PCL NFs 中与软骨基质降解、炎症和脂肪生成相关的基因表达水平降低。将 CHI-GA/CK/PCL NFs 植入软骨内可减少内侧半月板不稳定（DMM）手术引起的软骨降解。此外，通过上调 PPAR 减少了脂质沉积的积累和 IL-1β 的表达水平。
CHI-GA/CK/PCL NFs 通过抑制与软骨降解、炎症和脂肪生成相关的基因表达水平以及通过增加 PPAR 减少脂质积累和 IL-1β 的表达水平，有效治疗软骨缺陷。
