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经生物大分子和负载吡罗昔康的明胶纳米纤维改性的大孔支架表面,用于半月板软骨修复。

Macroporous scaffold surface modified with biological macromolecules and piroxicam-loaded gelatin nanofibers toward meniscus cartilage repair.

机构信息

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.

出版信息

Int J Biol Macromol. 2021 Jul 31;183:1327-1345. doi: 10.1016/j.ijbiomac.2021.04.151. Epub 2021 Apr 29.

DOI:10.1016/j.ijbiomac.2021.04.151
PMID:33932422
Abstract

Meniscus cartilage has poor self-healing capacity in the inner zone and its damage leads to articular cartilage degeneration. Here we have developed hybrid constructs using polycaprolactone (PCL) and polyurethane (PU) surface modified by gelatin (G), chitosan (C), and hyaluronic acid (H) biomacromolecules and piroxicam-loaded gelatin nanofibers (PCL/PU/GCH/P). The surface of constructs was crosslinked using EDC and NHS. The scaffolds were investigated by SEM, FTIR spectroscopy, swelling test, degradation rate, mechanical tests, and in vitro piroxicam release assay. Furthermore, the cell-seeded scaffolds were evaluated by SEM, viability assay, dapi staining, cell migration, proliferation, and gene expression of chondrocytes within these scaffolds. Finally, the animal study was performed in a rabbit model. Chondrocyte and rabbit adipose-derived mesenchymal stem cells (ASCs) from the infrapatellar fat pad (Hoffa's fat pad) were used. Swelling and degradation rate were increased in the modified scaffolds. Tensile and compressive Young's modulus also were near to human native meniscus tissue. The highest expression level of chondrocyte marker genes was observed for the PCL/PU/GCH scaffold. A significant regeneration was obtained in rabbits treated with ASCs-loaded PCL/PU/GCH/P scaffold after 3 months. The surface-modified scaffolds with or without ASCs could successfully accelerate meniscus regeneration and exhibit potential application in meniscus tissue engineering.

摘要

半月板软骨在内侧区域自我修复能力差,其损伤会导致关节软骨退化。在这里,我们使用聚己内酯(PCL)和聚氨酯(PU)开发了混合结构,其表面经过明胶(G)、壳聚糖(C)和透明质酸(H)生物大分子以及负载吡罗昔康的明胶纳米纤维(PCL/PU/GCH/P)改性。使用 EDC 和 NHS 对构建体的表面进行交联。通过 SEM、FTIR 光谱、溶胀试验、降解率、力学试验和体外吡罗昔康释放试验对支架进行了研究。此外,通过 SEM、活力测定、DAPI 染色、细胞迁移、增殖以及这些支架内软骨细胞的基因表达对细胞接种支架进行了评估。最后,在兔模型中进行了动物研究。使用来自髌下脂肪垫(Hoffa 脂肪垫)的软骨细胞和兔脂肪间充质干细胞(ASCs)。改性支架的溶胀和降解速率增加。拉伸和压缩杨氏模量也接近人体天然半月板组织。PCL/PU/GCH 支架的软骨细胞标志物基因表达水平最高。在 3 个月后,用负载 ASC 的 PCL/PU/GCH/P 支架治疗的兔子获得了显著的再生。表面改性的支架无论是否负载 ASC,都能成功促进半月板再生,并在半月板组织工程中具有潜在应用。

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