Tailorable Glycosaminoglycans for Enhanced Stem Cell Chondrogenesis

该奖项由材料研究部的生物材料项目授予格鲁吉亚理工学院，旨在开发一种基于糖胺聚糖（GAG）的生物材料平台，该平台具有高度的硫酸化水平控制，以便更好地调整这些材料作为受控生物分子递送载体，用于组织工程和药物递送系统。此外，使用间充质干细胞微团培养作为试验平台，这项工作将定义构建生物材料的有形标准，这些生物材料可以促进干细胞分化以响应外源性可溶性线索，同时提供有关GAG（及其硫酸化水平）在软骨发育中作用的早期信息。此外，由于GAG涉及如此广泛的生物过程，因此本文开发的材料可用于阐明GAG在发育，癌症和免疫中的作用（仅举几例），因此也为推进这些领域的基础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，在其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创造下一代可定制生物材料的关键问题。来自组织的生物材料，例如本项目中研究的那些，是有利的，因为它们通常具有与其环境相互作用并直接愈合的特定能力。然而，迄今为止，这些材料的复杂结构和无数可能的天然化学修饰使得难以理解如何精确控制它们的生物活性，因此阻碍了它们作为一类治疗性生物材料的发展。该项目通过采取系统的方法来了解这类特定生物材料的化学修饰如何影响其产生的生物活性和控制特定药物释放的能力来解决这个问题。虽然该项目首先将研究从这些材料中释放特定因子用于软骨组织再生，但在未来，预计这些研究中获得的见解将用于进一步开发这些天然来源的材料，以提供广泛的治疗方法用于整个身体的组织愈合。该项目还将导致研究生研究人员的高级培训，具有基于多学科和综合视角的独特分析技能。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，将为代表性不足的少数民族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.