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Osteochondral regeneration using scaffold-free constructs of adipose tissue-derived mesenchymal stem cells made by a bio three-dimensional printer with a needle-array in rabbits
Regenerative Therapy ( IF 3.4 ) Pub Date : 2020-07-24 , DOI: 10.1016/j.reth.2020.05.004
Daiki Murata , Yoshihiro Kunitomi , Kaori Harada , Satoshi Tokunaga , Shoko Takao , Koichi Nakayama

Osteoarthritis is a major joint disease for which medical interventions have been extensively investigated in humans and animals. In this study, we examined the regeneration of articular cartilage and subchondral bone using a scaffold-free construct consisting of adipose tissue-derived mesenchymal stem cells (AT-MSCs) fabricated using a bio three-dimensional (3D) printer. AT-MSCs were isolated from three rabbits and cultured to a number of sufficient for creation of 3D-printed constructs. One construct consisted of 960 spheroids obtained from 3.5 × 104 autologous AT-MSCs. The construct was then implanted into an osteochondral defect (diameter 4 mm and depth 4 mm) surgically bored into the left femoral trochlear groove of each rabbit. Three months after implantation, healing was assessed by computed tomography, magnetic resonance (MR) imaging, and pathology. MR images were evaluated based on a modified two-dimensional (2D)-magnetic resonance observation of cartilage repair tissue (MOCART) grading system, and gross and microscopic histology were scored according to the International Cartilage Repair Society scale. At the time of imaging, treated defects had become radiopaque, while control defects remained radiolucent. Total 2D-MOCART scores were higher in the implanted defects than in the controls, but not to a statistically significant extent. Similarly, average histological scores were comparable among all groups, although average gross scores were significantly higher in implanted defects than in controls. This is the first demonstration of a scaffold-free 3D-printed construct consisting of autologous AT-MSCs regenerating cartilage and subchondral bone within three months.



中文翻译:

使用生物三维打印机用针阵列在兔中使用无脂肪组织来源的间充质干细胞构建无支架的骨软骨再生

骨关节炎是一种主要的关节疾病,已经在人和动物中广泛研究了医疗干预措施。在这项研究中,我们使用无支架构建物检查了关节软骨和软骨下骨的再生,该构建物由使用生物三维(3D)打印机制造的脂肪组织来源的间充质干细胞(AT-MSC)组成。从三只兔子中分离出AT-MSC,并培养至足以产生3D打印构建体的数量。一种构建体由960个从3.5×10 4获得的球体组成自体AT-MSC。然后将该构建体植入外科手术钻入每只兔子的左股骨滑车槽的骨软骨缺损(直径4 mm,深度4 mm)中。植入后三个月,通过计算机断层扫描,磁共振(MR)成像和病理学评估愈合情况。基于改进的软骨修复组织(MOCART)分级二维(2D)磁共振观察评估MR图像,并根据国际软骨修复学会量表对肉眼和显微镜下的组织学评分。在成像时,已处理的缺陷变为不透射线,而对照缺陷仍保持射线可透。植入的缺损中的2D-MOCART总分高于对照组,但没有统计学上的显着性。同样,所有组的平均组织学评分均相当,尽管植入缺损的平均总评分明显高于对照组。这是无支架3D打印构建体的首次展示,该构建体由自体AT-MSC在三个月内再生软骨和软骨下骨组成。

更新日期:2020-07-24
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