Tailorable Glycosaminoglycans for Enhanced Stem Cell Chondrogenesis

这项由材料研究部生物材料项目授予佐治亚理工学院的奖项是为了开发一种基于糖胺聚糖(GAG)的生物材料平台，该平台具有高度可控的硫化水平，以便更好地调整这些材料作为受控生物分子输送载体，用于组织工程和药物输送系统的应用。此外，使用间充质干细胞微团培养作为试验床，这项工作将定义构建生物材料的具体标准，这些材料可以响应外部可溶信号促进干细胞分化，同时提供有关GAG在软骨发育中的作用(及其硫化水平)的早期信息。此外，由于GAG涉及如此广泛的生物过程，这里开发的材料可以用来阐明GAG在发育、癌症和免疫(举几个例子)中的作用，因此也对促进这些领域的基本生物学知识做出了重大贡献。更广泛的影响包括创造一个高度跨学科的环境，在这个环境中培养研究生和本科生生物学家、工程师和化学家，通过整合材料科学、化学、生物学和医学的知识来解决在创造下一代可定制生物材料中的关键问题。从组织中提取的生物材料，如本项目中所研究的生物材料，是有利的，因为它们通常具有与环境相互作用和直接愈合的特定能力。然而，到目前为止，这些材料的复杂结构和无数可能的天然化学修饰使得人们很难理解如何准确地控制它们的生物活性，从而阻碍了它们作为一类治疗性生物材料的发展。本项目通过采用系统的方法来解决这一问题，以了解对这类特定生物材料的化学修饰如何影响其所产生的生物活性和控制特定药物释放的能力。虽然该项目首先将研究这些材料中用于软骨组织再生的特定因素的释放，但在未来，这些研究得出的见解将被用于进一步开发这些自然衍生材料，以提供广泛的治疗方法，用于全身组织愈合。该项目还将从多学科和综合的角度对具有独特分析技能的研究生研究人员进行高级培训。此外，计划中的综合教育和研究计划与校园外展方案相协调，将为来自代表性不足的少数族裔人口的本科生和高中生提供更多的培训机会。

This award by the Biomaterials program in the Division of Materials Research to the Georgia Institute of Technology is to develop a glycosaminoglycan (GAG)-based biomaterial platform with high degree of control of sulfation levels in order to better tune these materials as controlled biomolecule delivery vehicles for applications in tissue engineering and drug delivery system. Furthermore, using a mesenchymal stem cell micromass culture as a testbed, this work will define tangible criteria for building biomaterials that can promote stem cell differentiation in response to exogenous soluble cues while providing early information about the role of GAGs (and their sulfation level) in cartilage development. Additionally, because GAGs are implicated in such a wide range of biological processes, the materials developed here can be used to elucidate the role of GAGs in development, cancer, and immunity (to name a few examples), therefore contributing significantly to advancing basic biological knowledge in these fields as well. Further broader impacts include the creation of a highly interdisciplinary environment in which to train graduate and undergraduate biologists, engineers and chemists to address critical questions in creating the next generation of tailorable biomaterials by integrating knowledge from materials science, chemistry, biology and medicine.Biomaterials derived from tissues, such as those examined in this project, are advantageous because they often possess specific capabilities to interact with their environment and direct healing. However, the complex structure and myriad of possible native chemical modifications of these materials have, to date, made it difficult to understand how to precisely control their biological activity and, therefore, impeded their development as a class of therapeutic biomaterials. This project addresses this issue by taking a systematic approach to understanding how chemical modifications to this particular class of biomaterials affects their resulting bioactivity and ability to control release of specific drugs. While the project first will examine the release of specific factors from these materials for cartilage tissue regeneration, in the future, it is expected that the insights derived from these studies will be used to further develop these naturally-derived materials to deliver a wide range of therapeutics for tissue healing throughout the body. This project will also result in the advanced training of graduate researchers with unique analytical skills based on a multi-disciplinary and integrative perspective. Moreover, the planned integrated education and research plan in coordination with outreach programs on campus will result in additional training opportunities for undergraduate and high school students from under-represented minority populations.