球体
生物加工
组织工程
自愈水凝胶
细胞包封
生物材料
纳米技术
三维细胞培养
3D生物打印
材料科学
生物制造
生物医学工程
细胞
细胞培养
化学
生物
工程类
生物技术
高分子化学
生物化学
遗传学
作者
Nikolas Di Caprio,Jason A. Burdick
标识
DOI:10.1016/j.actbio.2022.09.052
摘要
Cellular spheroids are aggregates of cells that are being explored to address fundamental biological questions and as building blocks for engineered tissues. Spheroids possess distinct advantages over cellular monolayers or cell encapsulation in 3D natural and synthetic hydrogels, including direct cell-cell interactions and high cell densities, which better mimic aspects of many tissues. Despite these advantages, spheroid cultures often exhibit uncontrollable growth and may be too simplistic to mimic complex tissue structures. To address this, biomaterials are being leveraged to further expand the use of cellular spheroids for biomedical applications. In this review, we provide an overview of recent studies that utilize engineered biomaterials to guide spheroid formation and function, as well as their fabrication into tissues for use as tissue models and for therapeutic applications. First, we describe biomaterial strategies that allow the high-throughput fabrication of homogeneously-sized spheroids. Next, we summarize how engineered biomaterials are introduced into spheroid cultures either internally as microparticles or externally as hydrogel microenvironments to influence spheroid behavior (e.g., differentiation, fusion). Lastly, we discuss a variety of biofabrication strategies (e.g., 3D bioprinting, melt electrowriting) that have been used to develop macroscale tissue models and implantable constructs through the guided assembly of spheroids. Overall, the goal of this review is to provide a summary of how biomaterials are currently being engineered and leveraged to support spheroids in biomedical applications, as well as to provide a future outlook of the field. STATEMENT OF SIGNIFICANCE: Cellular spheroids are becoming increasingly used as in vitro tissue models or as 'building blocks' for tissue engineering and repair strategies. Engineered biomaterials and their processing through biofabrication approaches are being leveraged to structurally support and guide spheroid processes. This review summarizes current approaches where such biomaterials are being used to guide spheroid formation, function, and fabrication into tissue constructs. As the field is rapidly expanding, we also provide an outlook on future directions and how new engineered biomaterials can be implemented to further the development of biofabricated spheroid-based tissue constructs.
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