State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 8 Shuangqing Road, Haidian District, Beijing, 100085, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
J Nanobiotechnology. 2020 Jun 3;18(1):84. doi: 10.1186/s12951-020-00641-2.
Fracture incidence increases with ageing and other contingencies. However, the strategy of accelerating fracture repair in clinical therapeutics remain a huge challenge due to its complexity and a long-lasting period. The emergence of nano-based drug delivery systems provides a highly efficient, targeted and controllable drug release at the diseased site. Thus far, fairly limited studies have been carried out using nanomedicines for the bone repair applications. Perfluorocarbon (PFC), FDA-approved clinical drug, is received increasing attention in nanomedicine due to its favorable chemical and biologic inertness, great biocompatibility, high oxygen affinity and serum-resistant capability. In the premise, the purpose of the current study is to prepare nano-sized PFC materials and to evaluate their advisable effects on promoting bone fracture repair.
Our data unveiled that nano-PFC significantly enhanced the fracture repair in the rabbit model with radial fractures, as evidenced by increased soft callus formation, collagen synthesis and accumulation of beneficial cytokines (e.g., vascular endothelial growth factor (VEGF), matrix metalloprotein 9 (MMP-9) and osteocalcin). Mechanistic studies unraveled that nano-PFC functioned to target osteoblasts by stimulating their differentiation and activities in bone formation, leading to accelerated bone remodeling in the fractured zones. Otherwise, osteoclasts were not affected upon nano-PFC treatment, ruling out the potential target of nano-PFC on osteoclasts and their progenitors.
These results suggest that nano-PFC provides a potential perspective for selectively targeting osteoblast cell and facilitating callus generation. This study opens up a new avenue for nano-PFC as a promising agent in therapeutics to shorten healing time in treating bone fracture.
骨折发病率随着年龄的增长和其他意外情况而增加。然而,由于其复杂性和长期持续时间,在临床治疗中加速骨折修复的策略仍然是一个巨大的挑战。基于纳米的药物输送系统的出现为在患病部位提供高效、靶向和可控的药物释放提供了可能。到目前为止,使用纳米药物进行骨修复应用的研究相当有限。全氟碳化合物(PFC)是一种经过 FDA 批准的临床药物,由于其良好的化学和生物惰性、高生物相容性、高氧亲和力和抗血清能力,在纳米医学中受到越来越多的关注。在本研究中,目的是制备纳米级 PFC 材料,并评估其对促进骨骨折修复的适宜效果。
我们的数据显示,纳米 PFC 显著增强了兔桡骨骨折模型中的骨折修复,表现为软骨痂形成增加、胶原合成增加和有益细胞因子(如血管内皮生长因子(VEGF)、基质金属蛋白酶 9(MMP-9)和骨钙素)的积累。机制研究表明,纳米 PFC 通过刺激成骨细胞的分化和骨形成中的活性来靶向成骨细胞,从而加速骨折区域的骨重塑。此外,纳米 PFC 治疗对破骨细胞没有影响,排除了纳米 PFC 对破骨细胞及其前体的潜在作用靶点。
这些结果表明,纳米 PFC 为选择性靶向成骨细胞和促进骨痂生成提供了一种潜在的方法。这项研究为纳米 PFC 作为一种有前途的治疗药物开辟了新途径,可缩短治疗骨折的愈合时间。