Co-culture cell-derived extracellular matrix loaded electrospun microfibrous scaffolds for bone tissue engineering
Co-culture cell-derived extracellular matrix loaded electrospun microfibrous scaffolds for bone tissue engineering
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DOI：
10.1016/j.msec.2019.01.127
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发表时间：
2019-06-01
影响因子：
7.9
通讯作者：
Vashishth, Deepak
中科院分区：
文献类型：
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作者：
Carvalho, Marta S.;Silva, Joao C.;Vashishth, Deepak
细胞衍生的细胞外基质（ECM）已被用作组织工程的支架，创建仿生微环境，该仿生微环境为细胞提供物理、化学和机械刺激，并通过模拟其体内微环境来支持细胞粘附、增殖、迁移和分化。尽管细胞来源的ECM的生物活性增强，但其作为支架再生硬组织如骨的应用仍然受到其不足的机械性能的阻碍。细胞来源的ECM与合成生物材料的组合可能会导致一个有效的策略，以提高支架的机械性能和结构支持。静电纺丝已用于骨组织工程中以制造纤维和多孔支架，模仿ECM中发现的分级组织的纤维状结构和架构。虽然支架的结构可能类似于ECM架构，但由于缺乏生物活性和骨诱导因子，大多数这些静电纺丝支架未能实现功能。在这项研究中，我们开发了生物活性的细胞衍生的ECM静电纺丝聚己内酯（PCL）支架从ECM来源于人间充质干/基质细胞（MSC），人脐静脉内皮细胞（HUVEC）及其组合的基础上的假设，即细胞衍生的ECM纳入PCL纤维将增强支架的生物功能。本研究的目的是制造和表征细胞衍生的ECM电纺PCL支架，并评估其增强MSC成骨分化的能力，设想骨组织工程应用。我们的研究结果表明，与单独的PCL相比，所有细胞衍生的ECM电纺支架促进了显著的细胞增殖，同时呈现出相似的物理/机械特性。此外，MSC：HUVEC-ECM电纺支架显著增强了MSC的成骨分化，如通过增加的ALP活性和成骨基因表达水平所证实的。据我们所知，这些结果描述了第一项研究，表明MSC：HUVEC-ECM可能被开发为骨组织工程应用的仿生电纺支架。
Cell-derived extracellular matrix (ECM) has been employed as scaffolds for tissue engineering, creating a biomimetic microenvironment that provides physical, chemical and mechanical cues for cells and supports cell adhesion, proliferation, migration and differentiation by mimicking their in vivo microenvironment. Despite the enhanced bioactivity of cell-derived ECM, its application as a scaffold to regenerate hard tissues such as bone is still hampered by its insufficient mechanical properties. The combination of cell-derived ECM with synthetic biomaterials might result in an effective strategy to enhance scaffold mechanical properties and structural support. Electrospinning has been used in bone tissue engineering to fabricate fibrous and porous scaffolds, mimicking the hierarchical organized fibrillar structure and architecture found in the ECM. Although the structure of the scaffold might be similar to ECM architecture, most of these electrospun scaffolds have failed to achieve functionality due to a lack of bioactivity and osteoinductive factors. In this study, we developed bioactive cell-derived ECM electrospun polycaprolactone (PCL) scaffolds produced from ECM derived from human mesenchymal stem/stromal cells (MSC), human umbilical vein endothelial cells (HUVEC) and their combination based on the hypothesis that the cell-derived ECM incorporated into the PCL fibers would enhance the biofunctionality of the scaffold. The aims of this study were to fabricate and characterize cell-derived ECM electrospun PCL scaffolds and assess their ability to enhance osteogenic differentiation of MSCs, envisaging bone tissue engineering applications. Our findings demonstrate that all cell-derived ECM electrospun scaffolds promoted significant cell proliferation compared to PCL alone, while presenting similar physical/mechanical properties. Additionally, MSC:HUVEC-ECM electrospun scaffolds significantly enhanced osteogenic differentiation of MSCs as verified by increased ALP activity and osteogenic gene expression levels. To our knowledge, these results describe the first study suggesting that MSC:HUVEC-ECM might be developed as a biomimetic electrospun scaffold for bone tissue engineering applications.