PFI-TT: Validation of a Modular Osteoarthritis Disease Model System for Early Stage Pharmaceutical Drug Screening

该创新-技术转化伙伴关系（PFI-TT）项目的更广泛影响/商业潜力在于其解决骨关节炎（OA）的创新战略，骨关节炎是一种影响超过3250万美国成年人的广泛致残性疾病。该项目引入了一种“芯片联合”系统，这是一种用于早期药物测试的新模型，可能会彻底改变我们对OA的理解，并使变革性治疗的开发成为可能。这一举措还具有教育价值，为研究生提供创业技能，并为部落学院的本科生提供研究机会，从而在学术界和工业界之间建立了一个界面。该项目的商业潜力有望为微生理系统（MPS）蓬勃发展的全球市场注入活力。这些系统可以改善人类疾病建模，减少药物研究对动物研究的依赖，并为难以治愈的疾病（如OA）的开创性药物治疗打开大门。拟议项目的重点是开发一个独特的芯片上联合MPS平台。MPS作为降低药物开发成本和最大限度地减少对动物模型依赖的潜在工具已受到关注。该项目旨在建立一个系统，使用具有仿生微米级和纳米级生物物理线索的细胞培养支架来模拟人类关节的多组织结构。该项目中采用的创新方法增强了MPS中人类细胞行为的重演。目的是建立一个体外系统，能够有效地表征关节健康对研究药物的反应。此外，该项目旨在验证MPS在将骨关节炎建模为关节疾病方面的有效性，从而促进早期临床前药物开发研究。通过利用这一尖端技术，该项目致力于推进MPS领域，并为药物开发流程的完善做出贡献。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/commercial potential of this Partnerships for Innovation - Technology Translation (PFI-TT) project lies in its innovative strategy to tackle osteoarthritis (OA), a widespread, disabling condition affecting over 32.5 million US adults. The project introduces a 'joint-on-a-chip' system, a novel model for early-stage drug testing, potentially revolutionizing our understanding of OA and enabling the development of transformative treatments. This initiative also boasts educational merits, providing graduate students with entrepreneurial skills and offering research opportunities to undergraduates from tribal colleges, thereby creating an interface between academia and industry. The project's commercial potential is poised to invigorate the burgeoning global market for microphysiological systems (MPSs). These systems allow for improved human disease modeling, reducing dependence on animal studies in pharmaceutical research, and opening doors to pioneering pharmaceutical treatments for difficult to cure diseases like OA.The proposed project focuses on the development of a unique joint-on-a-chip MPS platform. MPSs have gained attention as potential tools to decrease drug development costs and minimize reliance on animal models. The project aims to establish a system that uses cell culture scaffolds with biomimetic microscale and nanoscale biophysical cues to model the multi-tissue structure of human articular joints. The innovative approach taken in this project enhances the recapitulation of human cellular behavior within the MPS. The goal is to establish an in vitro system capable of efficiently characterizing joint health in response to investigational drugs. Additionally, the project seeks to validate the effectiveness of the MPS in modeling osteoarthritis as a disease of the joint, thus facilitating early preclinical pharmaceutical drug development research. By leveraging this cutting-edge technology, the project endeavors to advance the MPS field and contribute to the refinement of drug development processes.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.