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含钆生物纳米复合材料修复兔膝关节软骨下骨缺损和关节软骨。

Repairing of Subchondral Defect and Articular Cartilage of Knee Joint of Rabbit by Gadolinium Containing Bio-Nanocomposites.

机构信息

Department of Orthopedics, The Third Affiliated Hospital of Qiqihar Medical College, Qiqihar 161000, Heilongjiang, China.

出版信息

J Biomed Nanotechnol. 2021 Aug 1;17(8):1584-1597. doi: 10.1166/jbn.2021.3106.

DOI:10.1166/jbn.2021.3106
PMID:34544536
Abstract

A variety of gadolinium (Gd) based nanoparticles (NPs) were synthesized due to the unique magnetic properties of Gd-containing rare earth compounds and the particularity of micro/nano-materials, which were then incorporated into hydroxyapatite (HA) to obtain inorganic-organic composite materials. Then, HA/Gd NPs containing slow-release transforming growth factor (TGF-β1) were harvested. Adipose-derived stem cells (ADSCs) were extracted from the adipose tissue of a four-month-old New Zealand white rabbit. HA/Gd NPs were attached to absorbable gelatin sponge to obtain HA/Gd NPs/gelatin sponge composite scaffold. In addition, the third generation ADSCs were taken and cultured in the composite scaffold, so that ADSCs-HA/Gd bio-nanocomposites were obtained. The in vitro culture test of osteoblast MC3T3-E1 showed that Gd-containing NPs had good biocompatibility. The prepared HA/Gd NPs loaded with TGF-β1 were spherical, with an average particle size of (9.16 ± 3.16) μm. The NPs were easy to aggregate and adherent. Enzyme-linked immunosorbent assay (ELISA) test results showed that TGF-β1 in NPs was sustained and released continuously for 29 days. HA/Gd NPs/gelatin sponge composite scaffold combined with ADSCs were co-cultured for three days, and the electron microscope showed that the HA/Gd NPs were dispersed, and the cells could adhere and grow well. Then, animal models of rabbit knee articular cartilage defects were established and were rolled into three groups (ADSCs-HA/Gd nano group, HA/Gd nano scaffold group, and blank control). The repair area of the rabbit knee of ADSCs-HA/Gd nano group was smooth and flat, the scaffold was absorbed, the toluidine blue stain was positive, and the type II collagen immunohistochemical stain was positive. In general, ADSCs-HA/Gd nanomaterials were helpful for chondrogenic cell differentiation and had certain adoption prospects in the field of tissue engineering to repair cartilage defects.

摘要

由于含钆稀土化合物的独特磁性和微/纳米材料的特殊性,合成了多种基于钆(Gd)的纳米颗粒(NPs),然后将其掺入羟基磷灰石(HA)中,以获得无机-有机复合材料。然后,收获含有缓慢释放转化生长因子(TGF-β1)的 HA/Gd NPs。从四个月大的新西兰白兔的脂肪组织中提取脂肪来源的干细胞(ADSCs)。将 HA/Gd NPs 附着在可吸收明胶海绵上,得到 HA/Gd NPs/明胶海绵复合支架。此外,取第三代 ADSCs 在复合支架中培养,得到 ADSCs-HA/Gd 生物纳米复合材料。成骨细胞 MC3T3-E1 的体外培养试验表明,含 Gd 的 NPs 具有良好的生物相容性。负载 TGF-β1 的 HA/Gd NPs 呈球形,平均粒径为(9.16±3.16)μm。 NPs 容易聚集和附着。酶联免疫吸附试验(ELISA)检测结果表明,NPs 中的 TGF-β1 持续释放 29 天。HA/Gd NPs/明胶海绵复合支架与 ADSCs 共培养 3 天,电镜显示 HA/Gd NPs 分散,细胞能良好附着生长。然后,建立了兔膝关节软骨缺损动物模型,并将其分为三组(ADSCs-HA/Gd 纳米组、HA/Gd 纳米支架组和空白对照组)。ADSCs-HA/Gd 纳米组兔膝关节修复区平整光滑,支架吸收,甲苯胺蓝染色阳性,Ⅱ型胶原免疫组化染色阳性。综上所述,ADSCs-HA/Gd 纳米材料有助于软骨细胞的成软骨分化,在组织工程修复软骨缺损领域具有一定的应用前景。

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