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首页> 外文期刊>Biomaterials Science >Hydrogel 3D in vitro tumor models for screening cell aggregation mediated drug response
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Hydrogel 3D in vitro tumor models for screening cell aggregation mediated drug response

机译:水凝胶3D体外肿瘤模型用于筛选细胞聚集介导的药物反应

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Hydrogel-based 3D in vitro models comprising tumor ECM-mimetic biomaterials exhibit superlative potential as preclinical testing platforms for drug discovery and bioperformance screening. However, during hydrogel design and testing stages, the ideal selection between cancer cell laden 3D models or spheroid embedded hydrogel platforms remains to be elucidated. Selecting a disease-mimicking cellular arrangement within ECM hydrogels is paramount for anti-cancer therapeutics performance evaluation and may lead to differential outcomes. To investigate the effects assigned to varying cellular-arrangement, we developed dense 3D spheroid microtumors and cell-laden MG-63 osteosarcoma platforms embedded in GelMA and Matrigel ECM-mimetic scaffolds. These platforms enabled cancer cells/3D microtissues maturation and lorlatinib drug performance screening. Initial 3D spheroids assembly via the liquid overlay technique, resulted in the fabrication of dense cellular aggregates with reproducible size, morphology and necrotic core formation, thus mimicking the native tumor. Upon in vitro maturation, MG-63 spheroids encapsulated in hydrogel scaffolds exhibited significantly higher invasion and drug resistance than their cell laden hydrogel counterparts. Such data reveals inherent physiological and drug response variances among randomly distributed osteosarcoma cells and 3D spheroid-laden hydrogels. Overall, this highlights the importance of evaluating different cellular aggregation states when designing ECM-mimetic hydrogels for in vitro tumor modeling and high-throughput screening of anti-cancer therapeutics.
机译:基于水凝胶的3D体外模型,包括肿瘤ECM - 模拟生物材料表现出用于药物发现和生物信息筛选的临床前测试平台的最优性潜力。然而,在水凝胶设计和测试阶段期间,癌细胞载客3D模型或球状嵌入式水凝胶平台之间的理想选择仍有待阐明。选择ECM水凝胶中的疾病模仿蜂窝织布置对于抗癌治疗性能评估至关重要,可能导致差异结果。为了研究分配给不同的细胞安排的效果,我们开发了嵌入在凝胶和Matrigel ECM模拟支架中的致密3D球形Microotors和Cell-Laden Mg-63骨肉瘤平台。这些平台使癌细胞/ 3D微调成熟和Lorlatinib药物性能筛选使能。通过液体覆盖技术的初始3D球体组装,导致致密细胞聚集体的制造具有可再现的大小,形态和坏死核心形成,从而模仿原生肿瘤。在体外成熟时,包封在水凝胶支架中的Mg-63球体表现出比其细胞升温水凝胶对应物显着更高的侵袭和耐药性。这些数据揭示了随机分布的骨肉瘤细胞和3D锭剂升温水凝胶中固有的生理和药物反应差异。总体而言,这突出了在设计ECM模拟水凝胶时评估不同细胞聚集状态的重要性,用于体外肿瘤建模和抗癌治疗剂的高通量筛选。

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