Monodisperse, Thermoresponsive Microgels Based on Poly(ethylene Glycol) Derivative Polymers

技术概述：单分散聚合物胶体的合成通常是研究自组装过程的第一步，对于纳米结构材料的制造尤其重要。目前可用的聚合物胶体包括聚苯乙烯，聚甲基丙烯酸甲酯（PMMA）和聚n -异丙基丙烯酰胺（PNIPAM）球及其衍生物。该项目的目标是基于聚乙二醇衍生物聚合物，加入聚苯乙烯、PMMA和PNIPAM这些众所周知的胶体，创造新的单分散、热敏性聚合物胶体。本研究的核心思想是用沉淀聚合法将聚乙二醇乙醚甲基丙烯酸酯（PEGETH2MA）、聚乙二醇甲基丙烯酸甲酯（PEGMEA）、聚乙二醇丙烯酸甲酯（PEGA）及其衍生物共聚合成这些胶体。前两个组分提供接近生理温度的低临界溶液温度（LCST），而第三个组分（PEGA）提供一个官能团。在适当的化学成分和反应条件下，可以得到尺寸分布非常窄的PEG衍生物微凝胶。因此，这些聚乙二醇衍生物微凝胶可以作为构建块来制造具有胶体晶体结构的水凝胶。这个拟议的项目包括五个具体目标。首先是合成和表征聚乙二醇衍生物微凝胶，这些微凝胶应该是单分散的，热响应的，并且具有官能团。二是合成可生物降解的PEG衍生物微凝胶，首先合成可生物降解的PEG-聚乳酸大分子，然后将其作为微凝胶的交联剂。通过建立聚乙二醇衍生物微凝胶的结晶动力学与微凝胶的柔软度（低力学模量）之间的关系，探索微凝胶的自组装过程。（目标3）将使用PEG衍生物微凝胶作为交联剂和光衍射晶格合成具有胶体晶体结构的水凝胶（目标4）。目标五将重点关注聚乙二醇微凝胶胶体体的制备，并建立一个理论模型来描述胶体体等凝胶壳的膨胀动力学。非技术总结：这个提议的项目是创新的，因为如果成功，它将导致一类新的聚合物胶体，具有热响应性能和单分散的尺寸分布。与聚苯乙烯球和PMMA球的疏水性不同，所提出的PEG衍生物颗粒具有亲水性，并且在生理温度附近具有热响应的体积相变。与弹性模量极其柔软的PNIPAM微凝胶不同，可行性研究表明，PEG衍生物微凝胶密度更大，硬度更硬，更容易形成晶体结构。此外，在过去的二十年中，对热响应性聚合物微凝胶的研究主要集中在PNIPAM及其衍生物上。然而，PNIPAM非凡的热敏特性尚未转化为生物医学上的突破。主要障碍之一是PNIPAM单体具有致癌性或致畸性。因此，寻找一种生物相容性聚合物微凝胶替代PNIPAM将是该领域的主要进展之一。建议项目将为两名研究生提供直接支持，并扩大代表性不足群体的参与。该项目将把本科教育工作与三个现有的促进研究经验的项目结合起来：德克萨斯州数学与科学学院、德州理工大学罗纳德·f·麦克奈尔学士学位后成就项目和NSF-UNT REU暑期项目。通过这一跨学科项目，研究生和本科生将在聚合物、胶体和纳米结构材料等快速发展的领域获得宝贵的实验和分析技能。在这项研究中建立的基础科学不仅会对聚合物科学产生影响，而且会对生物医学技术产生影响。

TECHNICAL SUMMARY:Synthesizing monodisperse polymer colloids is usually the first step toward the study of self-assembling processes and especially important for the fabrication of nanostructured materials. The current available polymer colloids include polystyrene, polymethyl methacrylate (PMMA) and poly-N-isopropylacrylamide (PNIPAM) spheres and their derivatives. The objective of this proposed project is to create new monodisperse, thermo-responsive polymer colloids based on poly(ethylene glycol) derivative polymers, joining in these well-known colloids of polystyrene, PMMA, and PNIPAM. The central idea is to synthesize these colloids with copolymerization of poly(ethylene glycol) ethyl ether methacrylate (PEGETH2MA), poly(ethylene glycol) methyl ether methacrylate (PEGMEA), poly(ethylene glycol) acrylate (PEGA) and their derivatives using precipitation polymerization method. The first two components give the low critical solution temperature (LCST) near the physiological temperature while the third component (PEGA) provides a functional group. Under proper chemical compositions and reaction conditions, PEG derivative microgels with a very narrow size distribution may be obtained. As a result, these PEG derivative microgels can be used as building blocks to fabricate hydrogels with colloidal crystal structures. This proposed project consists of five specific aims. The first is to synthesize and characterize PEG derivative microgels that should be monodisperse, thermoresponsive, and with functional groups. The second aim is to synthesize biodegradable PEG derivative microgels by first synthesizing biodegradable PEG-polylactic acid macromer and then using them as crosslinkers for microgels. Self-assembling processes of the PEG derivative microgels will be explored by establishing the relationship between crystallization kinetics with the softness (low mechanical modulus) of the microgels. (Aim 3) Hydrogels with colloidal crystalline structures will be synthesized using PEG derivative microgels as both crosslinkers and as a light diffraction lattice (Aim 4). Aim five will focus on preparation of PEG-microgels-based colloidosomes and build a theoretical model that will describe swelling kinetics of a gel shell such as colloidosomes.NON-TECHNICAL SUMMARY:This proposed project is innovative because if successful, it will lead to a new class of polymer colloids that have thermal responsive properties and monodisperse size distribution. In contrast to polystyrene spheres and PMMA spheres that are hydrophobic, the proposed PEG derivative particles are hydrophilic and have a thermally responsive volume phase transition near the physiological temperature. Different from PNIPAM microgels that are extremely soft in terms of elastic modulus, the PEG derivative microgels will be denser, harder and easier to form a crystalline structure as revealed by the feasibility study. Furthermore, in the past two decades the most research on thermally responsive polymer microgels has focused on PNIPAM and its derivatives. However, the extraordinary thermo-sensitive properties of PNIPAM have not been transferred into a biomedical breakthrough. One of the major hurdles is that PNIPAM monomer is carcinogenic or teratogenic. Thus, finding a biocompatible polymer microgel replacement of PNIPAM will be one of the major advancements in this field. The proposed project will provide direct support for two graduate students and broaden the participation of underrepresented groups. This program will integrate its undergraduate educational efforts with three existing programs that promote research experiences: the Texas Academy of Mathematics and Science, the Ronald F. McNair Post-baccalaureate Achievement Program at UNT, and NSF-UNT REU summer program. From this proposed inter-disciplinary project, both graduate and undergraduate students will gain valuable experimental and analytical skills in the rapidly growing fields of polymers, colloids and nanostructured materials. The basic sciences established in this research will have impacts not only in polymer sciences but also in biomedical technology.