EAGER: An Interfacial Approach to Artificial Red Blood Cells

EAGER：人工红细胞的界面方法

• 批准号: 1560709
• 负责人: jiandi wan
• 金额: $ 10.39万
• 依托单位: Rochester Institute of Tech
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-15 至 2018-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1560709&HistoricalAwards=false
• 关键词: EAGER; Interfacial; Approach; Artificial; Red

Wan, Jiandi CBET - 1560709 EAGER: An Interfacial Approach to Artificial Red Blood CellsRed blood cells (RBCs) deliver oxygen to tissues and are the essential component of blood. Significant loss of RBCs due to emergencies and/or combat injuries requires blood transfusion, a life-saving intervention. RBCs, however, can only be stored outside the body for 14 days and transfusion of stored RBCs has been linked to increased risks of sickness and death. Artificial RBCs that have the similar features with natural RBCs and an improved storage lifetime are expected to overcome the problems associated with natural RBCs. Furthermore, artificial RBCs can be utilized as drug delivery vehicles when specific drugs are incorporated, and thus provide novel therapeutic advances in drug delivery. Current methods used to generate artificial RBCs, however, fail to mimic either the shape or softness of natural RBCs or have limited oxygen delivery ability. Artificial RBCs-based drug delivery is also less studied. Here, we are planning to produce artificial RBCs using innovative nano/micro technologies that enable the recapitulation of key features of natural RBCs and development of artificial RBCs-based drug delivery system. Artificial RBCs play a critical role in blood transfusion, which is a commonly life-saving intervention, especially for emergencies and combat injuries. This is particularly true considering the risks associated with allogeneic blood transfusion such as exposure to blood borne pathogens and inaccurate cross-matching for blood types. In addition, blood storage lesion has been linked to increased morbidity and mortality in clinical trials, and thus has urged the research of alternative blood substitutes. Most developed artificial RBCs, however, have encountered shortcomings including tissue injuries, immune system suppression, and particularly the low hemoglobin encapsulation efficiency. Most importantly, all current artificial RBCs are used as oxygen carriers and do not have the ability to fulfill other key physiological functions of natural RBCs such as deformation-induced adenosine triphosphate release, which is known to be critically important in the regulation of vascular tone. Here, by using innovative microfluidic approaches and tailor-designed amphiphilic block copolymers at the molecular and nanoscale, we aim to develop artificial RBCs that mimic the morphological and mechanical properties of natural RBCs and are capable of controlled release of adenosine triphosphate. The research described in this proposal will provide innovative engineering strategies to produce artificial RBCs mimicking the morphological, mechanical, and biological functions of natural RBCs. Such results are expected to have an important positive impact, because in addition to significant advances in blood transfusion and drug delivery, what is learned will contribute to a broader understanding of multiphase flow in microfluidics, the interfacial dynamics of nanostructure materials and their interactions with surrounding biological media. Consequently, the proposed research is expected to provide unique and otherwise unattainable conceptual, experimental and therapeutic advances in nano-bio phenomena and processes. Furthermore, once such strategies are available, there is a promise that artificial RBCs can be used as a universal type of RBCs (no need to match blood types) for safe and urgent (on-spot) blood transfusion and controlled drug delivery, which will impact significantly the nation and the global society. In addition, our research aims are coupled to our educational and outreach programs, benefiting minority and underrepresented groups, K-12 students, and graduate and undergraduate students. In particular, the experimental projects in this proposal are excellent opportunities for training young researchers in timely questions, nano/micro technologies, high-speed imaging, data analysis, presentations skills, etc. Especially as nano/micro technology is a popular theme, and the various imaging tools and experimental methods are excellent training modules.

万建迪 CBET - 1560709 EAGER：人工红细胞的界面方法红细胞 (RBC) 向组织输送氧气，是血液的重要组成部分。由于紧急情况和/或战斗受伤而导致红细胞大量流失，需要输血，这是一种挽救生命的干预措施。然而，红细胞在体外只能储存 14 天，并且输注储存的红细胞会增加疾病和死亡的风险。人工红细胞具有与天然红细胞相似的特征并且具有更长的储存寿命，有望克服与天然红细胞相关的问题。此外，当掺入特定药物时，人工红细胞可以用作药物递送载体，从而在药物递送方面提供新的治疗进展。然而，目前用于生成人工红细胞的方法无法模仿天然红细胞的形状或柔软度，或者氧气输送能力有限。基于人工红细胞的药物输送研究也较少。在这里，我们计划使用创新的纳米/微米技术生产人工红细胞，从而能够重现天然红细胞的主要特征并开发基于人工红细胞的药物输送系统。人工红细胞在输血中发挥着至关重要的作用，输血是一种常见的挽救生命的干预措施，特别是在紧急情况和战伤时。考虑到与同种异体输血相关的风险，例如暴露于血源性病原体和血型交叉配型不准确，这一点尤其正确。此外，在临床试验中，血液储存病变与发病率和死亡率增加有关，因此敦促替代血液替代品的研究。然而，大多数开发的人工红细胞都遇到了缺点，包括组织损伤、免疫系统抑制，特别是血红蛋白封装效率低。最重要的是，目前所有的人工红细胞都用作氧载体，不具备天然红细胞的其他关键生理功能的能力，例如变形诱导的三磷酸腺苷释放，而这对于血管张力的调节至关重要。在这里，通过使用创新的微流体方法和在分子和纳米尺度上定制设计的两亲性嵌段共聚物，我们的目标是开发模仿天然红细胞的形态和机械特性并能够控制释放三磷酸腺苷的人工红细胞。该提案中描述的研究将提供创新的工程策略来生产模仿天然红细胞的形态、机械和生物功能的人工红细胞。这些结果预计将产生重要的积极影响，因为除了输血和药物输送方面的重大进展外，所学到的知识还将有助于更广泛地了解微流体中的多相流、纳米结构材料的界面动力学及其与周围生物介质的相互作用。因此，拟议的研究有望为纳米生物现象和过程提供独特的、其他方面无法实现的概念、实验和治疗进展。此外，一旦此类策略可用，人工红细胞有望作为通用型红细胞（无需匹配血型）用于安全紧急（现场）输血和控制药物输送，这将对国家和全球社会产生重大影响。此外，我们的研究目标与我们的教育和推广计划相结合，使少数群体和弱势群体、K-12 学生以及研究生和本科生受益。特别是，本提案中的实验项目是培训年轻研究人员及时提问、纳米/微米技术、高速成像、数据分析、演示技巧等方面的绝佳机会。特别是纳米/微米技术是一个热门主题，各种成像工具和实验方法都是很好的培训模块。

项目成果

Microfluidic assay of the deformability of primitive erythroblasts

原始红细胞变形能力的微流控测定

• DOI: 10.1063/1.4999949
• 发表时间: 2017
• 期刊: Biomicrofluidics
• 影响因子: 3.2
• 作者: Zhou, Sitong;Huang, Yu-Shan;Kingsley, Paul D.;Cyr, Kathryn H.;Palis, James;Wan, Jiandi
• 通讯作者: Wan, Jiandi