Development of Novel Three-Dimensional Printed Scaffolds for Osteochondral Regeneration
Development of Novel Three-Dimensional Printed Scaffolds for Osteochondral Regeneration
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DOI：
10.1089/ten.tea.2014.0138
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发表时间：
2015-01-01
影响因子：
4.1
通讯作者：
Zhang, Lijie Grace
中科院分区：
文献类型：
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作者：
Holmes, Benjamin;Zhu, Wei;Zhang, Lijie Grace
随着现代医学的进步，人们正在探索和开发各种方法来治疗严重的关节骨软骨缺损。然而，由于骨软骨缺陷固有的再生能力差、复杂的分层结构和不同的生物力学特性，治愈骨软骨缺陷仍然非常具有挑战性。本研究的目的是创建新型三维（3D）打印骨软骨支架，该支架具有优异的界面机械性能和生物相容性，以促进人骨髓间充质干细胞（MSC）生长和软骨分化。为此，我们设计并 3D 打印了一系列创新的双相 3D 模型，模拟关节关节的骨软骨区域。我们的机械测试结果表明，与同质设计相比，我们的具有关键结构的双相支架在压缩（最大杨氏模量为 31 MPa）和剪切（最大断裂强度为 5768 N/mm(2)）方面具有增强的机械特性。这些结果也与数值模拟相关。为了提高其生物相容性，支架的表面进一步用乙酰化胶原蛋白（骨软骨细胞外基质的主要成分之一）进行修饰。 MSC 增殖结果表明，胶原蛋白的掺入以及仿生设计的微观特征可以在体外 5 天后极大地促进 MSC 生长。两周的软骨形成分化结果表明，我们的新型支架（称为“关键”支架），无论有或没有表面胶原修饰，都显示出增强的软骨形成（例如，与均质对照相比，胶原修饰的关键支架上的糖胺聚糖、II 型胶原沉积和总蛋白含量增加了 130%、114% 和 236%）。
As modern medicine advances, various methodologies are being explored and developed in order to treat severe osteochondral defects in joints. However, it is still very challenging to cure the osteochondral defects due to their poor inherent regenerative capacity, complex stratified architecture, and disparate biomechanical properties. The objective of this study is to create novel three-dimensional (3D) printed osteochondral scaffolds with both excellent interfacial mechanical properties and biocompatibility for facilitating human bone marrow mesenchymal stem cell (MSC) growth and chondrogenic differentiation. For this purpose, we designed and 3D printed a series of innovative bi-phasic 3D models that mimic the osteochondral region of articulate joints. Our mechanical testing results showed that our bi-phasic scaffolds with key structures have enhanced mechanical characteristics in compression (a maximum Young's modulus of 31 MPa) and shear (a maximum fracture strength of 5768 N/mm(2)) when compared with homogenous designs. These results are also correlated with numerical simulation. In order to improve their biocompatibility, the scaffolds' surfaces were further modified with acetylated collagen (one of the main components in osteochondral extracellular matrix). MSC proliferation results demonstrated that incorporation of a collagen, along with biomimetically designed micro-features, can greatly enhance MSC growth after 5 days in vitro. Two weeks' chondrogenic differentiation results showed that our novel scaffolds (dubbed "key" scaffolds), both with and without surface collagen modification, displayed enhanced chondrogenesis (e.g., 130%, 114%, and 236% increases in glycosaminoglycan, type II collagen deposition, and total protein content on collagen-modified key scaffolds when compared with homogeneous controls).