SBIR Phase I: An Innovative Full-Thickness Human Skin Model for Increased Throughput Screening in Drug Discovery

这个小型企业创新研究(SBIR)第一阶段项目建议开发一种全厚度的体外人体皮肤模型，其格式能够提高化合物的筛选能力。该项目将1)开发生产成纤维细胞来源的真皮替代物的培养条件，2)使用这些方法以更高产量的形式制造皮肤模型，3)表征这些组织的生化、结构和功能特性。这一模型系统的建立将为药物筛选、经皮给药方法评估、皮肤毒理学测试和皮肤特异性疾病模型(如黑色素瘤)的开发提供一个一致的体外测试平台。开发的工艺改进将促进纸巾生产的自动化，并可能可扩展到更小的纸巾规格。这项研究的更广泛影响在于能够提供一种更可靠、更准确、更具成本效益的方法来确定药物和其他化合物对人体皮肤的影响。生物技术、制药和消费品公司投入大量资源来筛选新产品及其成分的皮肤毒性和渗透性。目前，测试通常是使用单层细胞或动物模型进行的，尽管有充分证据表明，这些系统无法准确预测人类的药物疗效，这是导致候选药物在临床试验中成本高昂、失败率高的原因之一。体外皮肤模型显示出提高筛选能力的潜力，但目前的模型昂贵且产量相对较低。建议的模型将提供准确、高效和具有成本效益的化学筛选，同时避免与动物试验相关的伦理和监管问题。

This Small Business Innovation Research (SBIR) Phase I project proposes to develop a full-thickness in vitro human skin model in a format enabling increased-throughput screening of compounds. The project will 1) develop culture conditions for production of fibroblast-derived dermal equivalents, 2) use these methods to manufacture skin models in a higher-throughput format, and 3) characterize the biochemical, structural, and functional properties of these tissues. Establishment of this model system will provide a consistent in vitro test platform for drug screening, assessment of transdermal delivery methods, dermal toxicology testing, and development of skin-specific disease models (i.e. melanoma). The developed process improvements will facilitate automation of tissue production and may be scalable to even smaller tissue formats. The broader impact of this research resides in the ability to provide a more reliable, accurate, and cost-effective method of determining the effects of drugs and other chemical compounds on human skin. Biotechnology, pharmaceutical, and consumer product companies devote substantial resources to screening new products and their components for dermal toxicity and permeability. Currently, testing is typically performed using monolayer cells or animal models, despite a well-documented inability for those systems to accurately predict drug efficacy in humans, a problem that contributes to the costly, high failure rate of drug candidates in clinical trials. In vitro skin models show the potential to improve screening capabilities, but current models are expensive and relatively low-throughput. The proposed model will provide accurate, efficient, and cost-effective chemical screening, while avoiding the ethical and regulatory concerns associated with animal testing.