CAREER: Development of a Multifunctional Polyester Platform and its Evaluation as an Instructive Matrix for Osteoblast Differentiation

摘要：由材料研究部生物材料项目和化学、生物工程、环境和运输系统部生物医学工程项目（ENG/CBET）共同资助的阿克伦大学CAREER奖旨在开发一种模块化多功能聚酯平台，该平台具有肽样功能基团，可用作干细胞分化的基质。高分子材料衍生的产品是现代生活中不可或缺的一部分，高分子科学已经解决了几个技术挑战。聚合物除了广泛用作商品和工程材料外，还广泛用于生物医学领域，用于制造植入物、缝合线、医用导管、伤口愈合产品等。尽管如此广泛的使用，这种合成材料的设计和性能远远落后于它们的能力，以匹配天然材料的性能，如胶原蛋白，提供必要的功能线索，以获得最佳的生物学结果，如伤口愈合或新组织的精确生长和成熟。该项目将确定天然材料（如胶原蛋白）与广泛使用的合成材料之间的关键区别，并提供合成聚合物材料平台的自下而上设计。这种模块化合成聚合物系统在完全开发后，将具有物理和生物特性，使其能够用于多种生物医学应用，如干细胞分化、抗菌剂和药物/蛋白质输送。该奖项旨在促进STEM领域下一代科学家的培训，并在化学、材料科学和生物学的界面上提供基础培训。该奖项专门为高中生、本科生和研究生提供研究机会。来自当地高中的社会和经济条件较差的学生将通过这个项目得到指导。此外，一组具有较强资质的高中生将有机会从事前沿研究。此外，该奖项还允许创建一套免费的在线教育视频，描述聚合物科学的基本原理。技术摘要：细胞与周围环境之间信息的关键传递者是细胞外基质（ECM），这些信息通过细胞与细胞外基质组分之间的特定结合和信号事件进行处理。尽管越来越多的临床生物医学需求正在探索合成生物材料，但由于在平衡材料的功能、反应可行性、可降解性、亲水性等参数方面的复杂性，目前生物材料在结合和信号传导方面提供所需特异性的能力仍处于起步阶段。该合同将支持新型垂坠功能化聚酯系统的开发，该系统旨在提供多肽和蛋白质中所见的功能性和特异性的优势，同时还具有合成材料提供的合成可重复性和可扩展性的优势。作为一个说明性的案例研究，这些多功能聚酯将作为成骨细胞分化的指导性基质进行研究，目的是将多功能聚酯系统的化学特征与干细胞的增殖和分化联系起来。这种模块化合成平台具有精确改变聚合物组成的能力，将在多种生物医学应用中发挥作用，例如药物/蛋白质递送、自组装系统、多价抑制剂和抗菌剂。参与这项研究的学生将在化学，材料科学和细胞生物学的界面工作，也将有机会了解他们的研究如何解决生物医学科学的基本需求。

Non-technical Abstract: This CAREER Award by the Biomaterials program in the Division of Materials Research, and co-funded by the Biomedical Engineering Program in the Division of Chemical, Bioengineering, Environmental and Transport Systems (ENG/CBET) to the University of Akron is to develop a modular multifunctional polyester platform with peptide-like functional groups to be used as a matrix for stem cell differentiation. Products derived from polymeric materials are an integral part of modern life and polymer science has addressed several technological challenges. In addition to their extensive use as commodity and engineering materials, polymers are also widely used in the biomedical field to make implants, sutures, medical catheters, wound healing products etc. In spite of such extensive use, the design and performance of such synthetic materials lags far behind in their ability to match the performance of natural materials such as collagen in providing the functional cues necessary for optimum biological outcomes, such as in wound healing or precise growth and maturation of new tissue. The project will identify the key differences between natural materials such as collagen and widely used synthetic materials and offers a bottom-up design of a synthetic polymeric material platform. This modular synthetic polymer system, when fully developed, will have the physical and biological properties that would enable their use in several biomedical applications such as for differentiation of stem cells, as antimicrobials and for drug/protein delivery. This CAREER award facilitates the training of the next generation of scientists in STEM fields and provides fundamental training at the interface of chemistry, materials science and biology. The award specifically provides research opportunities for high school, undergraduate and graduate students. Socially and economically disadvantaged students from local high schools will be mentored through this program. In addition a select group of high school students with strong credentials will have the opportunity to engage in cutting edge research. In addition, the award enables to create a suite of freely available online educational videos describing the fundamental principles of polymer science.Technical Abstract: The key transmitter of information between cells and their surroundings is the extracellular matrix (ECM) and this information is processed by specific binding and signaling events between cells and the components of the ECM. Although synthetic biomaterials are being explored for an increasing number of clinical biomedical needs, the ability of current biomaterials to provide the required specificity in binding and signaling is still in its infancy due to the complexity in balancing the material parameters of functionality, reaction feasibility, degradability, hydrophilicity etc. The award will support the development of a new pendant functionalized polyester system which aims to provide the advantages of functionality and specificity as seen in peptides and proteins while also having the advantages of synthetic reproducibility and scalability that synthetic materials provide. As an illustrative case study, these multifunctional polyesters will be investigated as an instructive matrix for osteoblast differentiation with the aim of correlating the chemical profile of the multifunctional polyester system with stem cell proliferation and differentiation. Such a modular synthetic platform with the ability to precisely vary the polymer composition will be useful in several biomedical applications such as drug/protein delivery, self-assembled systems, multi-valent inhibitors and as antimicrobial agents. Students engaged in this research will work at the interface of chemistry, materials science and cell biology and will also have the opportunity to understand how their research addresses fundamental needs in the biomedical sciences.