Dispersion of ceramic granules within human fractionated adipose tissue to enhance endochondral bone formation
Dispersion of ceramic granules within human fractionated adipose tissue to enhance endochondral bone formation
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陶瓷颗粒在人体脂肪组织中的分散以增强软骨内骨的形成
DOI：
10.1016/j.actbio.2019.11.046
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发表时间：
2020-01-15
影响因子：
9.7
通讯作者：
Scherberich, Arnaud
中科院分区：
文献类型：
--
作者：
Huang, Ru-Lin;Guerrero, Julien;Scherberich, Arnaud
由肥大软骨组成的材料工程，作为通过软骨内骨化（ECO）从头骨形成的生理模板，有望成为一类新的生物骨替代品。在这里，我们评估了陶瓷颗粒与分级的人脂肪组织（“纳米脂肪”）的组合诱导的骨形成的效率和再现性，然后在体外引发肥大软骨。将人纳米脂肪与不同体积比的陶瓷颗粒（0.2-1 mm）混合并培养以依次诱导增殖（3周）、软骨形成（4周）和肥大（2周）。将所得工程化构建体异位植入裸鼠中。陶瓷颗粒的存在调节组织的形成，在体外和体内。特别是，它们以1：16的比例分散在纳米脂肪中导致体外细胞数量和糖胺聚糖积累显著增加，以及体内骨形成的量和供体间重现性显著增加。我们的研究结果概述了一个战略，有效利用纳米脂肪骨再生在自体设置，现在应该在原位situation.Statement的意义在这项研究中，我们评估了骨形成的效率和再现性相结合的陶瓷颗粒和分馏的人脂肪组织，也被称为纳米脂肪，在体外引发成肥大软骨。当异位植入裸鼠体内时，所得到的工程化软骨结构导致骨和骨髓形成，比单独的纳米脂肪更可重复和更强烈。该项目评估了陶瓷颗粒对天然脂肪组织生态位内间充质祖细胞的功能和软骨形成分化的影响，并概述了纳米脂肪在自体环境中用于骨再生的有效应用的新策略。(C)2019 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Engineering of materials consisting of hypertrophic cartilage, as physiological template for de novo bone formation through endochondral ossification (ECO), holds promise as a new class of biological bone substitutes. Here, we assessed the efficiency and reproducibility of bone formation induced by the combination of ceramic granules with fractionated human adipose tissue ("nanofat"), followed by in vitro priming to hypertrophic cartilage. Human nanofat was mixed with different volumetric ratios of ceramic granules (0.2-1 mm) and cultured to sequentially induce proliferation (3 weeks), chondrogenesis (4 weeks), and hypertrophy (2 weeks). The resulting engineered constructs were implanted ectopically in nude mouse. The presence of ceramic granules regulated tissue formation, both in vitro and in vivo. In particular, their dispersion in nanofat at a ratio of 1:16 led to significantly increased cell number and glycosaminoglycan accumulation in vitro, as well as amount and inter-donor reproducibility of bone formation in vivo. Our findings outline a strategy for efficient utilization of nanofat for bone regeneration in an autologous setting, which should now be tested at an orthotopic site.Statement of significanceIn this study, we assessed the efficiency and reproducibility of bone formation by a combination of ceramic granules and fractionated human adipose tissue, also known as nanofat, in vitro primed into hypertrophic cartilage. The resulting engineered cartilaginous constructs, when implanted ectopically in nude mouse, resulted in bone and bone marrow formation, more reproducibly and strongly that nanofat alone. This project evaluates the impact of ceramic granules on the functionality and chondrogenic differentiation of mesenchymal progenitors inside their native adipose tissue niche and outlines a novel strategy for an efficient application of nanofat for bone regeneration in an autologous setting. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.