{"title":"用于药物安全性评估的毒性测试平台从二维发展到先进的三维生物打印技术","authors":"Rohin Shyam , Rinni Singh , Mukul Bajpai , Arunkumar Palaniappan , Ramakrishnan Parthasarathi","doi":"10.1016/j.bprint.2024.e00363","DOIUrl":null,"url":null,"abstract":"<div><div>The process involved in the discovery of novel drugs in medical sciences is challenging due to the time-intensive process that results in a high cost of development. Additionally, it is reported that 90 % of new drugs fail in clinical trials and cannot reach the market. One of the primary reasons for failure is that research laboratories and pharmaceutical companies have been relying exclusively on data derived from animal-based models for testing the efficacy and safety of newly developed drugs. These models do not completely recapitulate human physiology or pathophysiology, resulting in a lower translational rate. Further, the evaluation of toxicity of drugs to the human body requires a more robust and holistic approach. Researchers across the globe are focusing on developing <em>in vitro</em>3D models as alternatives to traditional animal testing to circumvent these challenges. These model systems could replicate and mimic the human physiological microenvironment, cellular interactions, and arrangements. <em>In vitro</em>3D models would provide improved methods to evaluate and comprehend drug response, thereby reducing the burden on animal usage. Further, reducing the time and costs associated with developing, screening, drug failure, and translation of drugs is also realizable. In this communication, existing <em>in vitro</em> 3D models that are used in the drug development process are reviewed. In addition, the advancements in using 3D bioprinting and organ-on-a-chip technologies towards generating human reconstructed tissues/organs are also highlighted. The challenges from a technological and regulatory perspective on adapting these alternate animal models are also discussed.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"43 ","pages":"Article e00363"},"PeriodicalIF":0.0000,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evolution of toxicity testing platforms from 2D to advanced 3D bioprinting for safety assessment of drugs\",\"authors\":\"Rohin Shyam , Rinni Singh , Mukul Bajpai , Arunkumar Palaniappan , Ramakrishnan Parthasarathi\",\"doi\":\"10.1016/j.bprint.2024.e00363\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The process involved in the discovery of novel drugs in medical sciences is challenging due to the time-intensive process that results in a high cost of development. Additionally, it is reported that 90 % of new drugs fail in clinical trials and cannot reach the market. One of the primary reasons for failure is that research laboratories and pharmaceutical companies have been relying exclusively on data derived from animal-based models for testing the efficacy and safety of newly developed drugs. These models do not completely recapitulate human physiology or pathophysiology, resulting in a lower translational rate. Further, the evaluation of toxicity of drugs to the human body requires a more robust and holistic approach. Researchers across the globe are focusing on developing <em>in vitro</em>3D models as alternatives to traditional animal testing to circumvent these challenges. These model systems could replicate and mimic the human physiological microenvironment, cellular interactions, and arrangements. <em>In vitro</em>3D models would provide improved methods to evaluate and comprehend drug response, thereby reducing the burden on animal usage. Further, reducing the time and costs associated with developing, screening, drug failure, and translation of drugs is also realizable. In this communication, existing <em>in vitro</em> 3D models that are used in the drug development process are reviewed. In addition, the advancements in using 3D bioprinting and organ-on-a-chip technologies towards generating human reconstructed tissues/organs are also highlighted. The challenges from a technological and regulatory perspective on adapting these alternate animal models are also discussed.</div></div>\",\"PeriodicalId\":37770,\"journal\":{\"name\":\"Bioprinting\",\"volume\":\"43 \",\"pages\":\"Article e00363\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-10-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bioprinting\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2405886624000356\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Computer Science\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioprinting","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2405886624000356","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Computer Science","Score":null,"Total":0}
引用次数: 0
摘要
在医学科学领域,发现新药的过程具有挑战性,因为时间密集,开发成本高昂。此外,据报道,90% 的新药在临床试验中失败,无法进入市场。失败的主要原因之一是,研究实验室和制药公司一直完全依赖动物模型得出的数据来测试新开发药物的疗效和安全性。这些模型并不能完全再现人体生理或病理生理学,导致转化率较低。此外,评估药物对人体的毒性需要更强大、更全面的方法。全球研究人员正致力于开发体外 3D 模型,以替代传统的动物试验,从而规避这些挑战。这些模型系统可以复制和模拟人体生理微环境、细胞相互作用和排列。体外三维模型将为评估和理解药物反应提供更好的方法,从而减轻使用动物的负担。此外,减少与药物开发、筛选、药物失效和转化相关的时间和成本也是可以实现的。本文回顾了药物开发过程中使用的现有体外三维模型。此外,还重点介绍了利用三维生物打印和芯片器官技术生成人体重建组织/器官的进展。此外,还从技术和监管的角度讨论了采用这些替代动物模型所面临的挑战。
Evolution of toxicity testing platforms from 2D to advanced 3D bioprinting for safety assessment of drugs
The process involved in the discovery of novel drugs in medical sciences is challenging due to the time-intensive process that results in a high cost of development. Additionally, it is reported that 90 % of new drugs fail in clinical trials and cannot reach the market. One of the primary reasons for failure is that research laboratories and pharmaceutical companies have been relying exclusively on data derived from animal-based models for testing the efficacy and safety of newly developed drugs. These models do not completely recapitulate human physiology or pathophysiology, resulting in a lower translational rate. Further, the evaluation of toxicity of drugs to the human body requires a more robust and holistic approach. Researchers across the globe are focusing on developing in vitro3D models as alternatives to traditional animal testing to circumvent these challenges. These model systems could replicate and mimic the human physiological microenvironment, cellular interactions, and arrangements. In vitro3D models would provide improved methods to evaluate and comprehend drug response, thereby reducing the burden on animal usage. Further, reducing the time and costs associated with developing, screening, drug failure, and translation of drugs is also realizable. In this communication, existing in vitro 3D models that are used in the drug development process are reviewed. In addition, the advancements in using 3D bioprinting and organ-on-a-chip technologies towards generating human reconstructed tissues/organs are also highlighted. The challenges from a technological and regulatory perspective on adapting these alternate animal models are also discussed.
期刊介绍:
Bioprinting is a broad-spectrum, multidisciplinary journal that covers all aspects of 3D fabrication technology involving biological tissues, organs and cells for medical and biotechnology applications. Topics covered include nanomaterials, biomaterials, scaffolds, 3D printing technology, imaging and CAD/CAM software and hardware, post-printing bioreactor maturation, cell and biological factor patterning, biofabrication, tissue engineering and other applications of 3D bioprinting technology. Bioprinting publishes research reports describing novel results with high clinical significance in all areas of 3D bioprinting research. Bioprinting issues contain a wide variety of review and analysis articles covering topics relevant to 3D bioprinting ranging from basic biological, material and technical advances to pre-clinical and clinical applications of 3D bioprinting.