CAREER: Mechano-Responsive Biomaterials with Controlled Architectures and Improved Mechanical Properties via Biomimetic Strategies

特拉华大学的这个职业奖是由材料研究部的生物材料项目资助的。通过这个项目，PI将开发与天然细胞外基质的结构组织和多尺度响应性非常相似的生物材料，但具有可控的结构和改进的机械性能。该研究的主要重点将是：1)通过聚乙二醇与纳米颗粒的共价交联设计机械响应水凝胶，这些纳米颗粒表面具有牺牲键和隐藏长度，以模拟功能蛋白中的模块化结构域结构；2)通过再现天然弹性蛋白的分子结构，将天然弹性蛋白的疏水结构域替换为具有弹性反冲能力的合成聚合物，而将亲水结构域替换为具有潜在结构导向能力的特定肽序列，从而合成机械响应弹性体；3)通过微观和宏观方法表征这些动态和模块化生物材料的力学性能。虽然智能生物材料已被设计用于响应外部刺激，如pH值、温度、试剂、电场或磁场，但在人体内长时间对机械应力做出快速可逆响应的合成聚合物尚未开发出来。鉴于身体中的大多数组织都受到机械刺激，组织内的细胞具有积极响应机械力的复杂机制，因此在本项目中设计聚合物基质时考虑这种形式的信号传导是至关重要的。该提案旨在培养几名生物材料的研究生和本科生，并将他们与PI在机械响应生物材料方面的研究兴趣结合起来。开发一门新的生物医学工程研究生课程，向学生教授生物材料/生物医学概念，并激发他们对这些领域的兴趣，也是该项目的一部分。教育部分与拟议的研究活动紧密结合，目标是激励高中生从事生物材料/生物医学事业；并为少数族裔学生提供研究机会，让他们在生物材料研究方面有实践经验。拟议的研究和教育活动的跨学科性质也将使研究生掌握最新的信息，实验技能和创造性思维，这些都是不断发展的生物医学工程领域不可或缺的。最终目标是建立研究和教育计划，不仅将通过产生具有前所未有的机械性能和响应性的生物材料来推进生物医学工程领域，而且还将激励和教育下一代生物医学工程师和科学家。

This Career award to University of Delaware is funded by the Biomaterials program in the Division of Materials Research. With this project, the PI will develop biomaterials that closely resemble the structural organizations and multi-scale responsiveness of the natural extracellular matrices, but with controlled architectures and improved mechanical properties. Main focus of the proposed study will be: 1) design of mechano-responsive hydrogels by covalent cross-linking of polyethylene glycol with nanoparticles exhibiting sacrificial bonds and hidden length on their surfaces to mimic the modular domain structures present in functional proteins; 2) synthesis of mechano-responsive elastomers by recapitulating the molecular architecture of natural elastin whereby the hydrophobic domain of the native elastin is replaced with a synthetic polymer that is capable of elastic recoil, while the hydrophilic domain will be replaced with specific peptide sequences with potential structural directing capability; and 3) characterization of mechanical properties of these dynamic and modular biomaterials by microscopic and macroscopic methods. Although smart biomaterials have been designed to respond to external stimuli such as pH, temperature, reagents, electrical or magnetic fields, synthetic polymers with the ability to respond rapidly and reversibly to mechanical stresses over prolonged periods of time in the human body have yet to be developed. Given the fact that most tissues in the body are subjected to mechanical stimuli, and cells within the tissues have sophisticated machinery that actively responds to the mechanical force, it is critical that this form of signaling will be considered in the design of polymeric matrices in this project.The proposal aims to educate several graduate and undergraduate students in biomaterials and integrates them with PI's research interest in mechano-responsive biomaterials. Developing a new graduate level course in biomedical engineering to teach biomaterials/biomedical concepts to students and stimulate their interest in these areas is also part of this project. The educational component is closely integrated with the proposed research activities with the goals of inspiring high school students to pursue biomaterials/biomedical careers; and providing research opportunities for under-represented minority students with hands-on experiences in biomaterials research. The interdisciplinary nature of the proposed research and education activities will also equip graduate students with up-to-date information, experimental skills, and creative thinking that are all indispensable in the growing field of biomedical engineering. The ultimate goal is to establish research and education programs that will not only advance the field of biomedical engineering by generating biomaterials with unprecedented mechanical properties and responsiveness but also to inspire and educate the next generation of biomedical engineers and scientists.