CAREER: Multi-scale cell-fluid-matrix interactions during freezing/thawing of biological tissues

奖项摘要这个职业项目的目标是建立一个高度跨学科的生物运输研究和教育计划，桥接热科学/工程，生物学和医学，重点是定量了解冷冻/解冻诱导的生物组织内的多尺度细胞-流体-基质相互作用。 生物组织的冷冻出现在生物医学应用中以治疗患病组织（即，冷冻疗法）或保存组织（即，冷冻保存）。 尽管在细胞水平上取得了成功，但冷冻医学在组织系统中的应用仍然具有挑战性，并且由于其结果高度依赖于组织类型，因此其功效明显有限。 因此，相同的宏观规模冻融（F/T）方案可能导致成功或失败，这取决于冷冻/解冻的组织类型。 虽然F/T诱导的细胞、间质液和细胞外基质之间的相互作用被认为是导致组织类型依赖性结果的原因，但目前缺乏对细胞-液-基质相互作用的定量理解。 因此，许多应用依赖于经验驱动的策略或直接适应细胞水平的知识。 在这个研究项目中，这些多尺度的相互作用将被测量和表征在中/微米/纳米尺度上使用新开发的量子点介导的多模态测量技术。 拟议的研究活动的结果将建立一个框架的F/T诱导的细胞-液体-基质相互作用的机制的理解。 此外，还将开展以下三项教育活动：1）采用挑战驱动的教学方法开发跨学科的生物运输课程; 2）开发面向中学生的推广项目; 3）对参与的研究生和本科生进行跨学科研究和教学培训。 拟议的研究和教育活动的协同整合将通过将研究结果和发展直接体现在生物运输课程和推广计划的挑战驱动的教育模块中来实现。教育活动的最终成果将是为工程，生物和医学的跨学科领域招聘和培养未来的劳动力。 智力MeritThe拟议的研究将提供定量时空的理解F/T诱导的细胞-流体-基质的相互作用，这是一个缺失的环节桥梁宏观尺度的F/T协议的分子（纳米尺度），细胞（微观尺度），和组织（中尺度）水平的热量和质量传输现象。由此产生的全面理解将提供F/T诱导的细胞-流体-基质相互作用的机理见解以及热，机械和生物刺激的作用，这显着提高了我们对F/T诱导的生物转运现象的知识和理解。 此外，多尺度框架的拟议研究将大大推进我们的理解与新兴的微和纳米多孔系统的相变的移动边界问题。更广泛的影响这个CAREER项目有显着的社会影响，改善医疗保健，包括微创冷冻治疗癌症和心血管疾病，和冷冻保存天然组织移植手术。 此外，工程化细胞/组织的成功冷冻保存而不丧失其功能性是细胞/组织工程行业的关键使能技术。 拟议的项目还将通过挑战驱动的生物运输课程，推广计划和研究培训协同促进教学，培训和学习。 西班牙裔学生的参与将通过AHETEMS（推进西班牙裔卓越的技术，工程，数学和科学）基金会，其总部设在UT阿灵顿积极追求。 量化生物材料的多尺度细胞-流体-基质相互作用的新设施将提供给当地的医疗机构和工业。 为了广泛传播知识，最新的研究结果和开发的教育/外展模块将通过PI的实验室网站分发。

AWARD ABSTRACTThe goal of this CAREER project is to establish a highly interdisciplinary biotransport research and education program bridging thermal science/engineering, biology and medicine focused on quantitative understanding of freezing/thawing-induced multi-scale cell-fluid-matrix interaction within biological tissues. Freezing of biological tissue is emerging in biomedical applications to treat diseased tissues (i.e., cryotherapy) or to preserve tissues (i.e., cryopreservation). In spite of its success at the cellular level, the utilization of cryomedicine in tissue systems is still challenging and its efficacy is significantly limited since its outcomes are highly tissue-type dependent. Thus, an identical macro-scale freezing/thawing (F/T) protocol can result in either success or failure, depending on what kinds of tissues are frozen/thawed. Although F/T-induced interactions among cells, interstitial fluid and extracellular matrix are thought to cause the tissue-type dependent outcomes, quantitative understanding of the cell-fluid-matrix interactions is currently lacking. Thus, many applications rely on empirically driven strategies or directly adapt cellular level knowledge. In this research project, these multi-scale interactions will be measured and characterized at the meso/micro/nano-scales using a newly developed quantum dot-mediated multi-modal measurement technique. The outcomes of the proposed research activities will build a framework of mechanistic understanding of F/T-induced cell-fluid-matrix interactions. This understanding will ultimately help to design successful cryomedical applications for a wide variety of tissues.In addition, the following three educational activities will be performed - 1) development of an interdisciplinary biotransport course using the challenge-driven teaching method; 2) development of outreach programs for middle schoolers; and 3) interdisciplinary research and pedagogical training of participating graduate and undergraduate students. The synergistic integration of the proposed research and educational activities will be achieved by the direct embodiment of the research findings and developments into the challenge-driven education modules for the biotransport course and outreach programs. The ultimate outcomes of the educational activities will be the recruitment and preparation of a future workforce for interdisciplinary fields of engineering, biology and medicine. Intellectual MeritThe proposed research will provide quantitative spatiotemporal understanding of F/T-induced cell-fluid-matrix interactions, which is a missing link to bridge macro-scale F/T protocols to molecular (nano-scale), cellular (micro-scale), and tissue (meso-scale) level heat and mass transport phenomena. The resultant comprehensive understanding will give mechanistic insights on F/T-induced cell-fluid-matrix interactions and the role of thermal, mechanical and biological stimuli, which significantly enhance our knowledge and understanding on F/T-induced biotransport phenomena. In addition, the multi-scale framework of the proposed research will substantially advance our understanding of moving boundary problems with phase change in emerging micro- and nano-porous systems.Broader ImpactsThis CAREER project has significant societal impacts on improving healthcare including minimally invasive cryotherapies for cancers and cardiovascular disease, and cryopreservation of native tissues for transplantation surgeries. In addition, successful cryopreservation of engineered cell/tissue without losing their functionality is a crucial enabling technology for the cellular/tissue engineering industry. The proposed project will also synergistically promote teaching, training and learning through the challenge-driven biotransport course, outreach programs, and research training. Participation of Hispanic students will be actively pursued through AHETEMS (Advancing Hispanic Excellence in Technology, Engineering, Math and Science) Foundation, whose headquarters is located at UT-Arlington. The new facilities to quantify multi-scale cell-fluid-matrix interactions of biomaterials will be available to local medical institutes and industry. For broad dissemination of knowledge, the latest research findings and developed education/outreach modules will be distributed through the PI's laboratory website.