Dynamic and Reversible Control over Biological Signals in Hydrogel Matrices

非技术：该奖项由科罗拉多大学博尔德分校材料研究部生物材料项目颁发，由化学、生物工程、环境和运输系统（ENG）部门的生物技术、生化和生物质工程项目共同资助。该奖项支持成体干细胞的潜在治疗损伤或病变组织的研究。虽然这些基于细胞的疗法为恢复功能和提高生活质量提供了可能的途径，但目前它们在转化方面的局限性包括无法控制干细胞的分化，移植细胞的存活率低等。向这些细胞提供正确信号的生物材料系统可以帮助克服许多这些问题。为了满足这一重大需求，该项目将开发用于培养骨髓干细胞的先进生物材料系统，这些材料和方法将使我们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。我们期望这项研究将转化为新的生物材料系统，用于输送成体干细胞，从而提高其安全性和有效性。在这项研究中，研究生将接受生物学与工程学结合的最先进方法的培训，并为国家需要领域的科学事业做好准备（如生物材料、医疗设备和药物输送）。该团队还将整合本科生和高中生，作为通过外展项目向当地公众传播这项工作的持续努力的一部分。除了公布可广泛获取的结果外，我们还将继续为来访的中学生、教师和家长开发动手演示，因为3D成像细胞的视觉方面吸引了许多未来科学家和工程师的关注和兴奋。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。hMSCs是一种成体干细胞，在许多临床试验中被用于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hMSCs的界面上引入重要的生物信号。该方法利用了硫烯反应机制，特别是烯丙基硫化物的功能。许多含硫醇的生物大分子（如蛋白质、多肽）可以通过可逆交换反应与天然硫化物结合，从而允许用户控制支架生化功能的修饰。由于骨髓间充质干细胞的扩展和控制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骨髓间充质干细胞培养的系统，以及设计用于治疗应用的改进的骨髓间充质干细胞运载工具。作为这项研究的一部分，不同层次的学生（高中、本科和研究生）将接受聚合物和肽合成、生物偶联技术、水凝胶表征、干细胞培养和先进的光学显微镜方法的培训。从这项研究中获得的知识将被整合到高级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项目与公众交流。

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.