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

非技术摘要：这项由材料研究部生物材料项目和化学、生物工程、环境和运输系统部门生物医学工程项目(ENG/CBET)共同资助给阿克伦大学的职业奖项旨在开发一种具有多肽功能基团的模块化多功能聚酯平台，用作干细胞分化的基质。从聚合物材料衍生的产品是现代生活中不可或缺的一部分，聚合物科学已经解决了几个技术挑战。除了广泛用作商品和工程材料外，聚合物还广泛应用于生物医学领域，用于制造植入物、缝合线、医疗导管、伤口愈合产品等。尽管用途如此广泛，但此类合成材料的设计和性能远远落后于胶原等天然材料的性能，无法提供最佳生物结果所需的功能提示，如伤口愈合或新组织的精确生长和成熟。该项目将确定胶原蛋白等天然材料和广泛使用的合成材料之间的主要区别，并提供一种自下而上的合成聚合物材料平台设计。这种模块化的合成聚合物系统在完全开发后，将具有物理和生物特性，使其能够用于几种生物医学应用，如干细胞分化、作为抗菌剂和药物/蛋白质输送。这一职业奖旨在促进STEM领域下一代科学家的培训，并提供化学、材料科学和生物学方面的基础培训。该奖项专门为高中生、本科生和研究生提供研究机会。通过这项计划，当地高中的社会和经济困难学生将得到指导。此外，一批学历优秀的高中生将有机会从事尖端研究。此外，该奖项还允许创建一套免费提供的在线教育视频，描述聚合物科学的基本原理。技术摘要：细胞与其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ECM组件之间的特定结合和信号事件进行处理。尽管合成生物材料正在被探索以满足越来越多的临床生物医学需求，但由于在平衡功能性、反应可行性、降解性、亲水性等材料参数方面的复杂性，目前的生物材料在结合和信号传递方面提供所需的特异性的能力仍处于起步阶段。该奖项将支持开发一种新的悬挂式功能化聚酯系统，旨在提供多肽和蛋白质中所看到的功能性和专一性的优势，同时还具有合成材料提供的合成重复性和可扩展性的优势。作为一个说明性的案例研究，这些多功能聚酯将被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性与干细胞的增殖和分化相关联。这种能够精确改变聚合物组成的模块化合成平台将在多种生物医学应用中发挥作用，如药物/蛋白质递送、自组装系统、多价抑制剂和作为抗菌剂。从事这项研究的学生将从事化学、材料科学和细胞生物学的研究，并将有机会了解他们的研究如何满足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.