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首页> 外文会议>World biomaterials congress >Electrospun fibrous platforms as 3D in vitro model for screening chemotherapeutic drug effect in tissue regeneration and cancer therapy
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Electrospun fibrous platforms as 3D in vitro model for screening chemotherapeutic drug effect in tissue regeneration and cancer therapy

机译：电纺纤维平台作为3D体外模型，用于筛选组织再生和癌症治疗中的化学治疗药物作用

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Introduction: All tissues - i.e., healthy and cancerous ones - are composed of cells regulating body processes, maintenance and wound healing, and the extracellular matrix (ECM) - a chemically and structurally complex matter able to dynamically influence phenotypic/not phenotypic cell involved in regeneration and degeneration processes. Recently, much more attention has been referred to the definition of 3D in vitro tissue models able to reproduce ECM functionalities, by controlling molecular transport for an optimal administration of biochemical signals (i.e., growth factors, drugs) to guide cells fate in different ways. In this context, engineered scaffolds may provide a support matrix with ECM-like physical/structural properties suitable to in vitro reproduce all the main functionalities that healthy tissue or tumor microenvironment exert in vivo. In particular, electrospinning is emerging as an interesting micro/nano-fabrication technique to develop 3D platforms to predict the effect of chemotherapeutic drugs on in vitro cell activities. Here, we investigate how Poly-ε-caprolactone (PCL) electrospun scaffolds may influence the behavior of hMSC or tumor cells (i.e., hepatocarcinoma) in response to different chemotherapeutic molecules administration in order to validate their use as in vitro model for tissue engineering and cancer therapy. Materials and Methods: PCL fibers were produced by electrospinning technique, dissolving the polymer in chloroform (0.33 g/ml). hMSC and Hep G2 cells were seeded onto PCL electrospun fibers. Cell survival was analyzed by MTT assay. In particular, hMSC differentiation was analyzed by YIP-1B expression in presence or in absence of 5-AZA (1 and 5uM). Meanwhile, Hep G2 proliferation was evaluated by Brdu ELISA in the presence of doxorubicin (0.4 and 0.8 μM). In both cases, qualitative cell attachment was observed by FESEM analysis. Results and Discussion: We demonstrated that PCL fibers did not exert a cytotoxic effect on hMSCs, whereas they may reduce Hep G2 cell viability compared to plate control. SEM clearly showed hMSC and Hep G2 adhesion onto electrospun PCL fibers. Brdu assay suggested that PCL without doxorubicin significantly inhibited Hep G2 proliferation compared to plate control, but did not improve the effect of doxorubicin on Hep G2 proliferation. Contrariwise, in the case of hMSCs treated with 5-AZA, PCL fibers significantly increased YIP-1B expression - as index of myogenic differentiation, compared to plate control. Conclusion: We demonstrate that 3D fibrous network with the structural organization of ECM collagen fibers may influence interactions among cells mediated by chemotherapeutic drugs. This may open new interesting routes in drug administration to minimize side effects while preserving therapeutic benefits, thus concurring to the definition of more efficacious preclinical models for tissue regeneration/degeneration.
机译：介绍：所有组织 - 即健康和癌症的组织 - 由调节身体过程，维持和伤口愈合的细胞组成，细胞外基质（ECM） - 一种化学和结构性复杂物质，能够动态地影响表型/不是所涉及的表型细胞再生和变性过程。最近，通过控制用于最佳生化信号（即生长因子，药物）的分子传输来引导细胞命运的分子传输，更加重视能够再现ECM功能的3D体外组织模型的关注。在这方面，工程支架可以提供支持基质与ECM状适于体外再生的所有主要功能的物理/结构性质，健康的组织或体内肿瘤微环境使出。特别地，静电纺丝作为一种有趣的微/纳米制造技术，以开发3D平台以预测化学治疗药物对体外细胞活性的影响。在这里，我们研究如何聚ε己内酯（PCL）电支架可能影响的hMSC的行为或肿瘤细胞（即，肝癌）响应于不同化疗分子施用，以验证其用作体外模型用于组织工程和癌症疗法。材料和方法：通过静电纺丝技术生产PCL纤维，将聚合物溶解在氯仿中（0.33g / ml）。将HMSC和HEPG2细胞接种到PCL电纺纤维上。通过MTT测定分析细胞存活。特别地，通过在存在或不存在5-AZA（1和5um）的情况下通过YIP-1B表达分析HMSC分化。同时，通过Brdu ELISA在多柔比星（0.4和0.8μm）存在下评估HEP G2增殖。在这两种情况下，通过FESEM分析观察到定性细胞附着。结果与讨论：我们证明PCL纤维对HMSC而言并未对其进行细胞毒性作用，而它们可以减少与板控制相比的HEP G2细胞活力。 SEM清楚地显示出HMSC和HEPG2粘附到Electrom ow PCL纤维上。 Brdu测定表明，与板控制相比，没有多柔比蛋白的PCL显着抑制了HEP G2增殖，但没有改善多柔比星对肝脏G2增殖的影响。相反，在用5-AZA处理的HMSCs的情况下，与板控制相比，PCL纤维显着增加了YIP-1B表达显着增加 - 作为肌遗传分化的指数。结论：我们证明了具有ECM胶原纤维的结构组织的3D纤维网络可能影响化学治疗药物介导的细胞之间的相互作用。这可能会在药物管理局中开辟新的有趣路线，以尽量减少副作用，同时保持治疗益处，因此同时调整用于组织再生/变性更有效的临床前模型的定义。

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