The preliminary investigation on mechanism of preventing spinal interface osteolysis via surface-modified tissue-engineered cage

Honggang Guo, S. Feng, Yuebin Zhou, Fang-Lian Yao, Yinzhong Liu, Zhi Chen, Y. Liang, Tao Wang
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Abstract

Objective To evaluate the interrelationship between intervertebral osteolysis and inflammatory or osteoclastic gene expression. Methods Adipose derived stromal cells (ADSCs) were osteoinduced, conventioanl tissue-engineered (TE) and surface-modified TE cage constructs were establisehd. Anterior cervical fusion model of goat was established. Implantation was carried out according to following six group: surface-modified TE cage group [Nd: YAG+ RGD+ β- tricalcium phosphate (β-TCP)/chitosan (CS)/polycaprolactone (PCL) cage+ ADSCs], TE cage group (β-TCP/CS/PCL cage+ ADSCs), non-modified β-TCP/CS/PCL cage, hydroxyapatite (HA) cage, titanium and bone allograft cage. Three-dimensional CT was used to observe morphology changing, bone mineralization ratio, new bone mension and osteoblatic quantity, interleukin-6 (IL-6), metalloprotease-1 (MMP-1), tumor necrosis factor-α (TNF-α) and tartrate resistant acid phosphatase (TRAP), and osteoprotein (OPG) gene expression were detected at 2, 4, 8, 12, 16, 20, 24, 28 and 36 weeks. Biomechanical property was also detected at different interval. Results Compared with other groups, implant subsidence and migration were not found in surface-modified TE cage group. Meanwhile, new bone prolifreated remarkably with satisfactory data of bone mineralization ratio, and new bone mension or osteoblatic quantity [(63.9±1.3)%, (76.54±1.8)%, (73.8±2.3) cells]. IL-6, MMP-1, TNF-α and TRAP gene downregulated (0.09±0.01, 0.13±0.02, 0.08±0.01). Conversely, Runx2 and OPG gene upregulated (0.73±0.13, 0.57±0.16). In addition, data of bone strength and rang of motion in surface-modified TE cage group were significantly higher than those of other groups [(4.38±0.25) Nm/degree, (6.55±0.19)°]. Conclusion Invertebral osteolysis can be effectively controlled by surface-modified TE approach, and this provides a potential therapy for implant aseptic loosening. Key words: Osteolysis; Cage; Surface modification; Tissue engineering; Interface
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表面修饰组织工程支架预防脊髓界面骨溶解机制的初步研究
目的探讨椎间骨溶解与炎症或破骨细胞基因表达的相关性。方法采用骨诱导脂肪源性基质细胞(ADSCs),建立常规组织工程(TE)和表面修饰的TE笼结构。建立山羊颈前路融合术模型。根据以下六组进行植入:表面修饰的TE笼组[Nd:YAG+RGD+β-磷酸三钙(β-TCP)/壳聚糖(CS)/聚己内酯(PCL)笼+ADSCs]、TE笼组(β-TCP/CS/PCL笼+ADSCs)、非修饰的β-TCP/CS/PCL笼、羟基磷灰石(HA)笼、钛和同种异体骨笼。用三维CT观察2、4、8、12、16、20、24、28和36周时骨形态变化、骨矿化率、新骨尺寸和清骨量、白细胞介素-6(IL-6)、金属蛋白酶-1(MMP-1)、肿瘤坏死因子-α(TNF-α)和酒石酸抗性酸性磷酸酶(TRAP)的变化,并检测骨蛋白(OPG)基因的表达。在不同的时间间隔也检测到生物力学特性。结果与其他组相比,表面修饰TE笼组未发现种植体下沉和迁移。同时,新骨明显增生,骨矿化率、新骨尺寸或清骨量[(63.9±1.3)%,(76.54±1.8)%,[(73.8±2.3)个细胞]数据令人满意。IL-6、MMP-1、TNF-α和TRAP基因下调(0.09±0.01、0.13±0.02、0.08±0.01)。相反,Runx2和OPG基因上调(0.73±0.13、0.57±0.16)。此外,表面修饰TE笼组的骨强度和运动范围明显高于其他组[(4.38±0.25)Nm/度,(6.55±0.19)°]。关键词:骨溶解;笼;表面改性;组织工程;接口
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