Liu Bin, Li Junqin, Lei Xing, Miao Sheng, Zhang Shuaishuai, Cheng Pengzhen, Song Yue, Wu Hao, Gao Yi, Bi Long, Pei Guoxian
Department of Orthopedics, Xijing Hospital, Fourth Military Medical University Xi'an 710032 P. R. China
Department of Orthopedics, Linyi People's Hospital Linyi 276000 P. R. China.
RSC Adv. 2020 Jul 7;10(43):25652-25661. doi: 10.1039/d0ra03040f. eCollection 2020 Jul 3.
Injectable hydrogels have long been gaining attention in the bone tissue engineering field owing to their ability to mix homogeneously with cells and therapeutic agents, minimally invasive administration, and seamless defect filling. Despite the advantages, the use of injectable hydrogels as cell delivery carriers is currently limited by the challenge of mimicking the natural microenvironment of the loaded cells, promoting cell proliferation, and enhancing bone regeneration. To overcome these problems, we aimed to develop an injectable and -forming nanocomposite hydrogel composed of gelatin, alginate, and LAPONITE® to mimic the architecture and composition of the extracellular matrix. The encapsulated rat bone marrow mesenchymal stem cells (rBMSCs) survived in the nanocomposite hydrogel, and the gel promoted cell proliferation . Systematic research of the biomimetic hydrogel with or without cells was conducted in a critical-size (8 mm) rat bone defect model. The results proved that the hydrogel loaded with rBMSCs significantly promoted bone healing in rat calvarial defects, compared to the hydrogel without cells, and that the hydrogel did not provoked side effects on the recipients. Given these advantageous properties, the developed cell-loaded injectable nanocomposite hydrogel can greatly accelerate the bone healing in critical bone defects, thus providing a clinical potential candidate for orthopedic applications.
由于可注射水凝胶能够与细胞和治疗剂均匀混合、微创给药以及无缝填充缺损,长期以来一直受到骨组织工程领域的关注。尽管具有这些优点,但目前将可注射水凝胶用作细胞递送载体受到挑战,即难以模拟负载细胞的自然微环境、促进细胞增殖以及增强骨再生。为了克服这些问题,我们旨在开发一种由明胶、藻酸盐和锂皂石组成的可注射且可成型的纳米复合水凝胶,以模拟细胞外基质的结构和组成。封装在其中的大鼠骨髓间充质干细胞(rBMSCs)在纳米复合水凝胶中存活,并且该凝胶促进了细胞增殖。在临界尺寸(8毫米)的大鼠骨缺损模型中对含细胞和不含细胞的仿生水凝胶进行了系统研究。结果证明,与不含细胞的水凝胶相比,负载rBMSCs的水凝胶显著促进了大鼠颅骨缺损处的骨愈合,并且该水凝胶对受体没有引发副作用。鉴于这些有利特性,所开发的负载细胞的可注射纳米复合水凝胶可以极大地加速临界骨缺损处的骨愈合,从而为骨科应用提供一种具有临床潜力的候选材料。