Research Initiation Award: Designing Synthetic Polyglycidol-based Polymeric Networks to Influence Cellular Behavior

研究启动奖为传统黑人学院和大学的初级和中期职业教师提供支持，他们正在建立新的研究项目或重新指导和重建现有的研究项目。期望该奖项有助于提高教师的研究能力和效率，改善所在机构的研究和教学，并使本科生参与研究经验。菲斯克大学提出的跨学科研究有可能促进我们对生物系统和高分子材料之间相互作用的理解。此外，该项目涉及来自科学技术工程和数学领域代表性不足的少数群体的本科生。本研究的跨学科性质将为来自不同背景的本科生提供综合研究训练，从而使他们接触到最先进的聚合物化学研究的多学科性质。更广泛的影响扩展到全国，因为学生参与这个项目将进一步为他们进入一流的研究生学位课程和聚合物科学与工程或相关领域的职业生涯做好准备，从而使国家的科学技术工程和数学劳动力多样化。将生物化学和生物物理特性的战略性工程应用到当前的水凝胶技术中，但取得的成功有限，部分原因是缺乏功能性生物相容性聚合物和开发下一代合成生物材料所需的简易合成方法。本研究的目的是验证一个假设，即聚甘油基水凝胶的化学成分和网络拓扑结构可以很容易地调整，同时呈现多种生物物理和生化线索，然后可以用来调节间充质干细胞的附着、增殖和分化。为了实现这一目标，该项目结合了一系列已建立的合成方案，以产生一种新的简便方法，用于合成拓扑结构和组成独特的聚乙二醇基水凝胶，这是目前基于聚乙二醇的方法无法实现的。研究小组首先研究了交联动力学、网络拓扑结构和组成对水凝胶网络粘弹性特性的影响，然后利用分子和细胞生物学方法研究了将间充质干细胞纳入这些聚合物网络时的行为，作为聚合物拓扑结构和组成的功能。这种方法使研究小组能够在聚合物网络的生化和生物物理性质与细胞反应之间建立结构-性能-活性关系。对聚醚基网络进行简单的修饰，使其包含多种生物物理和生化特性，这代表了在设计细胞支架方面取得的重大进展，可用于获得对这些特性对细胞行为的协同效应的基本理解，推进用合成材料影响细胞过程所需的知识。该奖项反映了美国国家科学基金会的法定使命，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。

Research Initiation Awards provide support for junior and mid-career faculty at Historically Black Colleges and Universities who are building new research programs or redirecting and rebuilding existing research programs. It is expected that the award helps to further the faculty member's research capability and effectiveness, improve research and teaching at the home institution, and involves undergraduate students in research experiences. The interdisciplinary research proposed at Fisk University has the potential to advance our understanding of the interactions between biological systems and polymeric materials. Additionally, this project involves undergraduate students from underrepresented minority groups in the Science Technology Engineering and Mathematics fields. The interdisciplinary nature of this research will provide integrated research training to undergraduate students from multiple backgrounds, thereby exposing them to the multidisciplinary nature of state-of-the art polymer chemistry research. The broader impact extends nationwide as student participation in this project will further prepare them for matriculation to top-ranked graduate degree programs and to careers in polymer science and engineering or related fields, thereby diversifying the nation’s Science Technology Engineering and Mathematics workforce.The strategic engineering of biochemical and biophysical properties into current hydrogel technologies has been met with limited success, due in part to the scarcity of functional biocompatible polymers and facile synthetic methodologies needed for the development of next-generation synthetic biomaterials. The goal of this research is to test the hypothesis that the chemical composition and network topology of polyglycidol-based hydrogels can be easily tuned to present multiple biophysical and biochemical cues simultaneously, which can then be used to regulate mesenchymal stem cells attachment, proliferation, and differentiation. To accomplish this goal, this project combines a selection of established synthetic protocols to produce a new facile methodology for the synthesis of topologically and compositionally unique polyglycidol-based hydrogels, unattainable with current poly(ethylene glycol)-based methodologies. The research team first investigates the influence of crosslink kinetics, network topology, and composition on the viscoelastic properties of the hydrogel network, then access the behavior of mesenchymal stem cells when incorporated into these polymeric networks, as a function of polymer topology and composition, using molecular and cell biology approaches. This approach allows the research team to establish structure-property-activity relationships between the biochemical and biophysical properties of the polymeric network and cellular responses. The facile modification of polyether-based networks to include multiple biophysical and biochemical properties represents a significant advance towards designing cell-scaffolds that can be used to gain fundamental understanding of the synergistic effects of these properties on cellular behavior, advancing the knowledge needed to influence cellular processes with synthetic materials.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.