Dynamic and Reversible Control over Biological Signals in Hydrogel Matrices

水凝胶基质中生物信号的动态和可逆控制

• 批准号: 1408955
• 负责人: Kristi Anseth
• 金额: $ 40.5万
• 依托单位: University of Colorado at Boulder
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1408955&HistoricalAwards=false
• 关键词: Dynamic; Reversible; Control; over; Biological

Nontechnical:This award by the Biomaterials program in the Division of Materials Research to the University of Colorado at Boulder is cofunded by the Biotechnology, Biochemical, and Biomass Engineering program in the Division of Chemical, Bioengineering, Environmental, and Transport Systems (ENG). This award supports the study of adult stem cell for the potential treatment of injured or diseased tissues. While these cell-based therapies provide a possible avenue to restore function and improve quality of life, current limitations in their translation include the inability to control the differentiation of the stem cells, low survival of the transplanted cells, etc. Biomaterial systems that provide the right signals to these cells could help overcome many of these problems. To address this significant need, this project will develop advanced biomaterial systems for the culture of bone-marrow derived stem cells, and the materials and methods will allow us to better understand which signals are important and how they should be presented to the cells. We expect that this research will translate into new biomaterial systems for the delivery of adult stem cells that will improve their safety and efficacy. During this research, graduate students will be trained in state-of-the-art methods at the interface of biology with engineering, and prepared for scientific careers in areas of national need (e.g., biomaterials, medical devices, and drug delivery). The team will also integrate undergraduate students and high school students as part of a sustained effort to communicate this work to the local public through outreach programs. In addition to publication of results that will be broadly accessible, we will also continue to develop hands-on demonstrations for visiting secondary students, teachers and parents, as the visual aspects of imaging cells in 3D captures the attention and excitement of many prospective future scientists and engineers.Technical:This award supports the development of hydrogel biomaterials for the culture of human mesenchymal stem cells (hMSCs). hMSCs are adult stem cells that are being used in numerous clinical trials to promote healing of injured or diseased tissues. With this award, hydrogel scaffolds will be synthesized and characterized that allow one to introduce important biological signals at the interface of the biomaterial matrix with the hMSCs. The approach exploits a thiol-ene reaction mechanism and particularly an allyl-sulfide functionality. Many thiol-containing biomacromolecules (e.g., proteins, peptides) can be conjugated to the ally-sulfide moieity through reversible exchange reactions, which allow user-controlled modification of the scaffold biochemical functionality. Since the expansion and controlled differentiation of hMSCs often involves sequential presentation of biological signals, the materials developed as part of this award will allow us to study and engineer systems for improved culture of hMSCs, as well as design improved hMSC delivery vehicles for therapeutic applications. As part of this research, students at multiple levels (high school, undergraduate and graduate) will be trained in polymer and peptide synthesis, bioconjugation techniques, hydrogel characterization, stem cell culture and advanced light microscopy methods. The knowledge learned from this research will be integrated into course content in advanced Biomaterials and Tissue Engineering courses, as well as communicated to the general public through numerous outreach programs at the University of Colorado.

非技术性：该奖项由位于博尔德的科罗拉多大学材料研究部的生物材料项目授予，由化学、生物工程、环境和运输系统（ENG）部的生物技术、生物化学和生物质工程项目共同资助。该奖项支持成体干细胞用于受伤或患病组织的潜在治疗的研究。 虽然这些基于细胞的疗法提供了恢复功能和改善生活质量的可能途径，但目前在其翻译方面的限制包括无法控制干细胞的分化，移植细胞的存活率低等。 为了满足这一重大需求，该项目将开发用于培养骨髓源性干细胞的先进生物材料系统，这些材料和方法将使我们能够更好地了解哪些信号是重要的，以及它们应该如何呈现给细胞。 我们希望这项研究将转化为新的生物材料系统，用于输送成人干细胞，提高其安全性和有效性。 在这项研究中，研究生将在生物学与工程学的界面上接受最先进的方法培训，并为国家需求领域的科学事业做好准备（例如，生物材料、医疗器械和药物递送）。 该团队还将整合本科生和高中生，作为持续努力的一部分，通过推广计划将这项工作传达给当地公众。 除了公布成果，我们还将继续为来访的中学生、教师和家长开发实践演示，因为细胞3D成像的视觉方面吸引了许多未来科学家和工程师的注意力和兴奋。技术：该奖项支持用于培养人间充质干细胞（hMSCs）的水凝胶生物材料的开发。hMSC是成体干细胞，被用于许多临床试验，以促进受伤或患病组织的愈合。 有了这个奖项，水凝胶支架将被合成和表征，允许人们在生物材料基质与hMSC的界面处引入重要的生物信号。 该方法利用硫醇-烯反应机制，特别是烯丙基硫醚官能团。 许多含硫醇的生物大分子（例如，蛋白质、肽）可以通过可逆交换反应与烯丙基硫化物部分缀合，这允许使用者控制支架生物化学功能的修饰。 由于hMSC的扩增和受控分化通常涉及生物信号的顺序呈现，因此作为该奖项的一部分开发的材料将使我们能够研究和设计用于改进hMSC培养的系统，以及设计用于治疗应用的改进的hMSC递送载体。 作为这项研究的一部分，学生在多个层次（高中，本科和研究生）将在聚合物和肽合成，生物共轭技术，水凝胶表征，干细胞培养和先进的光学显微镜方法的培训。 从这项研究中学到的知识将被整合到先进的生物材料和组织工程课程的课程内容中，并通过科罗拉多大学的众多外展计划向公众传达。