Surface energy and stiffness discrete gradients in additive manufactured scaffolds for osteochondral regeneration
Surface energy and stiffness discrete gradients in additive manufactured scaffolds for osteochondral regeneration
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DOI：
10.1088/1758-5090/8/1/015014
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发表时间：
2016-03-01
期刊：
影响因子：
9
通讯作者：
Moroni, Lorenzo
中科院分区：
文献类型：
--
作者：
Di Luca, Andrea;Longoni, Alessia;Moroni, Lorenzo
生物支架技术的快速发展使发育生物学设计标准在再生医学三维支架中的应用取得了前所未有的进展。考虑到人体中的组织和器官按照特定的物理化学梯度发育，在这项研究中，我们假设增材制造（AM）技术将显著有助于构建包含此类梯度的3D支架。具体而言，我们考虑了表面能和刚度梯度，并分析了它们对成人骨髓间充质干细胞分化为骨骼谱系的影响。离散的逐步宏观梯度，通过顺序沉积不同的生物可降解的生物材料，即聚（乳酸）（PLA），聚己内酯（PCL），聚（环氧乙烷对苯二甲酸酯）/聚（对苯二甲酸丁二醇酯）（PEOT/PBT）共聚物在AM过程中，获得。在本体水平上，PEOT/PBT均质支架分别比PCL、PLA和梯度支架支持更高的碱性磷酸酶（ALP）活性。与离散梯度支架相比，所有均质生物材料支架也支持显著更高量的糖胺聚糖（GAG）产生。有趣的是，对不同材料隔室的分析揭示了PCL、PLA和PEOT/PBT对表面能梯度的特定贡献。而PEOT/PBT区域与显著更高的ALP活性相关，PLA区域与显著更高的GAG产生相关。这些结果表明，细胞活性可能受到3D支架中不同生物材料化学物质的特定空间分布的影响，并且工程表面能离散梯度可以被认为是设计骨软骨再生支架的吸引人的标准。
Swift progress in biofabrication technologies has enabled unprecedented advances in the application of developmental biology design criteria in three-dimensional scaffolds for regenerative medicine. Considering that tissues and organs in the human body develop following specific physico-chemical gradients, in this study, we hypothesized that additive manufacturing (AM) technologies would significantly aid in the construction of 3D scaffolds encompassing such gradients. Specifically, we considered surface energy and stiffness gradients and analyzed their effect on adult bone marrow derived mesenchymal stem cell differentiation into skeletal lineages. Discrete step-wise macroscopic gradients were obtained by sequentially depositing different biodegradable biomaterials in the AM process, namely poly(lactic acid) (PLA), polycaprolactone (PCL), and poly(ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT) copolymers. At the bulk level, PEOT/PBT homogeneous scaffolds supported a higher alkaline phosphatase (ALP) activity compared to PCL, PLA, and gradient scaffolds, respectively. All homogeneous biomaterial scaffolds supported also a significantly higher amount of glycosaminoglycans (GAGs) production compared to discrete gradient scaffolds. Interestingly, the analysis of the different material compartments revealed a specific contribution of PCL, PLA, and PEOT/PBT to surface energy gradients. Whereas PEOT/PBT regions were associated to significantly higher ALP activity, PLA regions correlated with significantly higher GAG production. These results show that cell activity could be influenced by the specific spatial distribution of different biomaterial chemistries in a 3D scaffold and that engineering surface energy discrete gradients could be considered as an appealing criterion to design scaffolds for osteochondral regeneration.