Department of Materials Science and Engineering, National Chiao Tung University, Hsinchu, Taiwan.
Department of Biomedical Engineering, I-Shou University, Kaohsiung, Taiwan.
Int J Nanomedicine. 2018 Jun 7;13:3177-3188. doi: 10.2147/IJN.S156284. eCollection 2018.
Stimulating the proliferation and differentiation of chondrocytes for the regeneration of articular cartilage is a promising strategy, but it is currently ineffective. Although both physical stimulation and growth factors play important roles in cartilage repair, their interplay remains unclear and requires further investigation. In this study, we aimed to clarify their contribution using a magnetic drug carrier that not only can deliver growth factors but also provide an external stimulation to cells in the two-dimensional environment.
We developed a nanocapsule (transforming growth factor-β1 [TGF-β1]-loaded magnetic amphiphilic gelatin nanocapsules [MAGNCs]; TGF-β1@MAGNCs) composed of hexanoic-anhydride-grafted gelatin and iron oxide nanoparticles to provide a combination treatment of TGF-β1 and magnetically induced physical stimuli. With the expression of Arg-Gly-Asp peptide in the gelatin, the TGF-β1@MAGNCs have an inherent affinity for chondrogenic ATDC5 cells.
In the absence of TGF-β1, ATDC5 cells treated with a magnetic field show significantly upregulated Col2a1 expression. Moreover, TGF-β1 slowly released from biodegradable TGF-β1@ MAGNCs further improves the differentiation with increased expression of Col2a1 and Aggrecan.
Our study shows the time-dependent interplay of physical stimuli and growth factors on chondrogenic regeneration, and demonstrates the promising use of TGF-β1@MAGNCs for articular cartilage repair.
刺激软骨细胞的增殖和分化以实现关节软骨再生是一种很有前途的策略,但目前效果不佳。虽然物理刺激和生长因子在软骨修复中都起着重要作用,但它们的相互作用尚不清楚,需要进一步研究。在这项研究中,我们旨在使用一种既能输送生长因子又能为二维环境中的细胞提供外部刺激的磁药物载体来阐明它们的作用。
我们开发了一种由己酸酐接枝明胶和氧化铁纳米粒子组成的纳米胶囊(转化生长因子-β1 [TGF-β1]负载的磁性两亲性明胶纳米胶囊[TGF-β1@MAGNCs]),以提供 TGF-β1 和磁诱导物理刺激的联合治疗。由于明胶中表达了精氨酸-甘氨酸-天冬氨酸肽,TGF-β1@MAGNCs 对软骨形成的 ATDC5 细胞具有固有亲和力。
在没有 TGF-β1 的情况下,经磁场处理的 ATDC5 细胞 Col2a1 的表达明显上调。此外,从可生物降解的 TGF-β1@ MAGNCs 缓慢释放的 TGF-β1 进一步改善了分化,Col2a1 和 Aggrecan 的表达增加。
我们的研究表明了物理刺激和生长因子对软骨生成再生的时间依赖性相互作用,并证明了 TGF-β1@MAGNCs 在关节软骨修复中的应用具有广阔的前景。