Liu Zhiqing, Ge Yuwei, Zhang Linyuan, Wang Yueting, Guo Cheng, Feng Kai, Yang Shengbing, Zhai Zanjing, Chi Yingjun, Zhao Jie, Liu Fengxiang
Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
J Tissue Eng Regen Med. 2020 Oct;14(10):1403-1414. doi: 10.1002/term.3106. Epub 2020 Aug 2.
The repair of large bone defects has always been a challenge, especially with respect to regeneration capacity and autogenous bone availability. To address this problem, we fabricated a 3D-printed polylactic acid (PLA) and hydroxyapatite (HA) scaffold (3D-printed PLA-HA, providing scaffold) loaded with enhanced bone marrow (eBM, providing seed cells) combined with induced membrane (IM, providing grow factors) to repair large radial defects in rabbits. in vitro assays, we demonstrated that 3D-printed PLA-HA had excellent biocompatibility, as shown by co-culturing with mesenchymal stem cells (MSCs); eBM-derived MSCs exhibited considerable differentiation potential, as shown in trilineage differentiation assays. To investigate bone formation efficacy in vivo, the rabbit radial long bone defect model was established. In the first stage, polymethylmethacrylate (PMMA) was inserted into the bone defect to stimulate the formation of IM; in the second stage, iliac crest bone graft (ICBG) with IM, PLA-HA alone with the removal of IM, PLA-HA with IM, and PLA-HA in conjunction with IM and eBM were sequentially applied to repair the long bone defect. At 8, 12, and 16 weeks, X-ray plain radiography, microcomputed tomography, and histological analysis were performed to evaluate the efficacy of bone repair and bone regeneration in each group. We found that IM combined with PLA-HA and eBM prominently enhanced bone repair and reconstruction, equivalent to that of IM/ICBG. Taken together, the data suggest that PLA-HA loaded with eBM combined with IM can be an alternative to IM with bone autografts for the treatment of large bone defects.
大骨缺损的修复一直是一项挑战,尤其是在再生能力和自体骨可用性方面。为了解决这个问题,我们制备了一种3D打印的聚乳酸(PLA)和羟基磷灰石(HA)支架(3D打印PLA-HA,提供支架),其负载增强骨髓(eBM,提供种子细胞)并结合诱导膜(IM,提供生长因子)来修复兔桡骨大缺损。在体外试验中,我们证明3D打印PLA-HA具有优异的生物相容性,与间充质干细胞(MSCs)共培养即可证明;eBM来源的MSCs表现出相当大的分化潜能,三系分化试验即可证明。为了研究体内骨形成效果,建立了兔桡骨长骨缺损模型。在第一阶段,将聚甲基丙烯酸甲酯(PMMA)插入骨缺损处以刺激IM形成;在第二阶段,依次应用带IM的髂嵴骨移植(ICBG)、单独去除IM的PLA-HA、带IM的PLA-HA以及结合IM和eBM的PLA-HA来修复长骨缺损。在第8、12和16周时,进行X线平片、微型计算机断层扫描和组织学分析,以评估每组的骨修复和骨再生效果。我们发现IM联合PLA-HA和eBM显著增强了骨修复和重建,与IM/ICBG相当。综上所述,数据表明,负载eBM并结合IM的PLA-HA可作为IM联合自体骨移植治疗大骨缺损的替代方法。