Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad 38000 Punjab, Pakistan.
Biomed Mater. 2021 Mar 9;16(4):042003. doi: 10.1088/1748-605X/abe6d8.
Advanced biomaterials are increasingly used for numerous medical applications from the delivery of cancer-targeted therapeutics to the treatment of cardiovascular diseases. The issues of foreign body reactions induced by biomaterials must be controlled for preventing treatment failure. Therefore, it is important to assess the biocompatibility and cytotoxicity of biomaterials on cell culture systems before proceeding to in vivo studies in animal models and subsequent clinical trials. Direct use of biomaterials on animals create technical challenges and ethical issues and therefore, the use of non-animal models such as stem cell cultures could be useful for determination of their safety. However, failure to recapitulate the complex in vivo microenvironment have largely restricted stem cell cultures for testing the cytotoxicity of biomaterials. Nevertheless, properties of stem cells such as their self-renewal and ability to differentiate into various cell lineages make them an ideal candidate for in vitro screening studies. Furthermore, the application of stem cells in biomaterials screening studies may overcome the challenges associated with the inability to develop a complex heterogeneous tissue using primary cells. Currently, embryonic stem cells, adult stem cells, and induced pluripotent stem cells are being used as in vitro preliminary biomaterials testing models with demonstrated advantages over mature primary cell or cell line based in vitro models. This review discusses the status and future directions of in vitro stem cell-based cultures and their derivatives such as spheroids and organoids for the screening of their safety before their application to animal models and human in translational research.
先进的生物材料越来越多地被用于各种医学应用，从癌症靶向治疗药物的输送到心血管疾病的治疗。必须控制生物材料引起的异物反应问题，以防止治疗失败。因此，在进行动物模型体内研究和随后的临床试验之前，在细胞培养系统上评估生物材料的生物相容性和细胞毒性非常重要。直接在动物身上使用生物材料会带来技术挑战和伦理问题，因此，使用非动物模型，如干细胞培养物，可能有助于确定其安全性。然而，未能再现复杂的体内微环境在很大程度上限制了干细胞培养物用于测试生物材料的细胞毒性。尽管如此，干细胞的特性，如其自我更新和分化为各种细胞谱系的能力，使它们成为体外筛选研究的理想候选物。此外，干细胞在生物材料筛选研究中的应用可能克服与使用原代细胞无法开发复杂异质组织相关的挑战。目前，胚胎干细胞、成体干细胞和诱导多能干细胞被用作体外初步生物材料测试模型，与基于成熟原代细胞或细胞系的体外模型相比具有明显优势。这篇综述讨论了体外基于干细胞的培养物及其衍生物（如球体和类器官）的现状和未来方向，用于在将其应用于动物模型和转化研究之前筛选其安全性。
