SBIR Phase II: A novel 3D bioprinting system for rapid high-throughput tissue fabrication

这个小型企业创新研究（SBIR）第二阶段项目的更广泛影响是提供一个高通量生物制品平台，可以为各种应用创建生理相关的体外组织模型，包括药物测试，检测开发，治疗和生物医学研究。目前的药物开发过程是漫长的，低效的，昂贵的。它耗资约18亿美元，需要12-15年才能推出一种药物。大约92%通过临床前测试的药物在随后的人体试验中失败，这突出表明缺乏足够的临床前测试工具来生成预测数据。在临床试验中未能检测到药物对人体重要器官的毒性，往往导致药物上市后退出市场，这给药物制造商造成了巨大的经济损失，也给患者带来了负面的身心影响。该技术将通过以高通量方式提供更可靠和临床相关的药物测试结果，显着提高药物安全性，提高效率并降低药物开发成本。这项技术还可以为关键的生物医学研究提供患者特异性组织（例如疾病建模）和体内治疗应用，提供一个可行的解决方案，以疾病没有治愈或有效的治疗尚未。这个小企业创新研究（SBIR）第二期项目将支持开发一个高通量生物制品平台，兼容高通量筛选（HTS）系统广泛用于药物筛选和检测开发。目前，传统的微制造策略和主流的基于生物打印机的关键瓶颈是缺乏可扩展性和吞吐量，以适应HTS系统中所需的可扩展制造。随着3D仿生人体组织模型在制药行业中的日益普及，迫切需要先进的制造系统，这些系统能够实现快速和简化的组织制造方法，这些方法与已经建立的HTS平台兼容，用于潜在候选药物的临床前毒性测试。拟议的项目将开发一个基于并行光学投影的3D生物打印平台，用于在HTS系统中常用的多孔板内直接制造3D组织。所提出的3D生物打印系统的实施将允许随后直接在威尔斯孔内进行原位药物筛选或测定测试，并大大提高制药行业和生物医学研究界的生物制造工作流程效率。这台生物打印机将作为一个强大的工具，用于在工业规模上大规模生产3D组织模型，以推进药物发现和检测开发。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact of this Small Business Innovation Research (SBIR) Phase II project is to provide a high-throughput biofabrication platform that can create physiologically relevant in vitro tissue models for diverse applications including drug testing, assay development, therapeutics, and biomedical research. The current drug development process is lengthy, inefficient, and expensive. It costs about $1.8 billion and takes 12-15 years to launch a single drug. Approximately 92% of the drugs that passed preclinical testing failed in subsequent human trials, highlighting the lack of adequate preclinical testing tools to generate predictive data. Failure to detect the drug-induced toxicity to the vital human organs in clinical trials often leads to market withdrawal of the drug after launch, which causes enormous financial losses to the drug manufacturer and also negative physical and mental effects for patients. The proposed technology will significantly improve drug safety, increase the efficiency and lower the cost of drug development by providing more reliable and clinically relevant drug testing results in a high-throughput fashion. This technology can also provide patient-specific tissues for critical biomedical research (e.g. disease modeling) and in vivo therapeutic applications, providing a viable solution to diseases without no cures or effective treatment yet.This Small Business Innovation Research (SBIR) Phase II project will support the development of a high-throughput biofabrication platform that is compatible with the high-throughput screening (HTS) systems widely used for drug screening and assay development. Currently, the key bottleneck for traditional microfabrication strategies and mainstream nozzle-based bioprinters is the lack of scalability and throughput to accommodate scalable manufacturing necessary in HTS systems. With the growing adoption of 3D biomimetic human tissue models in the pharmaceutical industry, there is a critical need for advanced manufacturing systems that enable rapid and streamlined tissue fabrication methods that are compatible with already established HTS platforms for preclinical toxicity testing of potential drug candidates. The proposed project will develop a parallel optical projection-based 3D bioprinting platform for direct manufacturing of 3D tissues within multiwell plates commonly used in the HTS systems. Implementation of the proposed 3D bioprinting system will permit subsequent in situ drug screening or assay testing directly within the wells and drastically improve biofabrication workflow efficiencies for the pharmaceutical industry and biomedical research community. This bioprinter will serve as a powerful instrument for the mass production of 3D tissue models at the industrial scale to advance drug discovery and assay development.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.