Functional Glycopolymer Tissue Engineering Scaffolds from a Natural Glycolipid with Chondrogenic and Anti-inflammatory Properties

非技术性：Rensselaer Polytechnic Institute的这一奖项旨在开发一种有效的策略，以修复与骨关节炎相关的软骨缺损，同时治疗经常传播关节退化的慢性炎症。目前的临床治疗软骨缺损可以暂时恢复关节功能。然而，这些方法不能治疗导致与骨关节炎相关的组织变性的慢性炎症循环。将开发一种组织工程支架，不仅恢复局部受损软骨的功能，而且随着支架降解，还提供抗炎分子持续释放到周围润滑滑液中。为了实现这一目标，PI将进一步开发一个独特的生物材料家族，该生物材料家族来源于由脂肪酸和糖残基组成的酵母细胞产生的天然结构单元。通过“绿色化学”方法制备的聚合物将被调整，使得它们具有组织工程支架所需的生物学特性。此外，在生物材料执行其功能后，它将水解降解为安全分子。哲学博士、参加该计划的本科生和高中生将获得现代有机和聚合物合成，生物催化，细胞生物学方法以及将生物材料制造成所需形式的关键技能。学生将在团队中工作，学习关键的沟通技巧，并将发展跨学科研究问题的深刻理解。技术：拟议的研究旨在开发一种组织工程策略，以修复与骨关节炎相关的软骨缺损，同时治疗经常传播关节退化的慢性炎症。拟议研究的目标是：1）开发通过酵母产生的内酯糖脂的开环易位聚合（ROMP）合成的糖共聚物的文库，所述内酯糖脂用一系列已知为软骨形成和/或抗炎的特定化学部分修饰，2）生成和表征多孔糖基共聚物生物材料支架，和3）通过体外研究评估软骨形成和抗-这些支架的炎症特性，以确定支架的未来在体内评价。这项工作的一个关键策略是使用内酯型槐糖脂（LSL）作为结构单元，因为它们很容易通过发酵以高产率（300 g/L）生产。此外，LSL在聚合之前或之后都适合于广泛的选择性改性反应，这为生物可吸收生物材料提供了平台，其结构和功能特性可以根据需要进行“调整”。高中本科和博士学生将被组织成团队，以便：i）为不同级别的学生提供指导机会; ii）模拟当今越来越多地利用跨学科团队解决复杂问题的工作场所。通过这种方式，学生在程序将获得高层次的团队合作和学科之间的沟通的理解和欣赏。

Non-technical:This award to Rensselaer Polytechnic Institute is to develop an effective strategy to repair cartilage defects associated with osteoarthritis while also treating chronic inflammation which often propagates joint deterioration. Current clinical treatments for cartilage defects can temporarily restore joint function. However, these methods fail to treat the chronic inflammatory cycle that contributes to tissue degeneration associated with osteoarthritis. A tissue engineering scaffold will be developed that not only restores the function of locally damaged cartilage but also provides for the sustained release of anti-inflammatory molecules into the surrounding lubricating synovial fluid as the scaffold degrades. Toward this goal, the PI will further develop a unique family of biomaterials derived from a natural building block produced by yeast cells that consists of fatty acid and sugar residues. The polymers, prepared by a "green chemistry" approach, will be tuned so that they have the required biological properties needed for the tissue engineering scaffold. Furthermore, after the biomaterial performs its function, it will hydrolytically degrade to safe molecules. Ph.D., undergraduate and high school students participating in this program will gain critically important skills in modern organic and polymer synthesis, biocatalysis, cell-biology methods and in the fabrication of biomaterials into desired forms. Students will work in teams, learn critical communication skills and will develop a deep appreciation for interdisciplinary research problems. Technical:The proposed research seeks to develop a tissue engineering strategy to repair cartilage defects associated with osteoarthritis while also treating chronic inflammation which often propagates joint deterioration. Objectives in the proposed studies are to: 1) develop a library of glycopolymers synthesized by the ring-opening metathesis polymerization (ROMP) of a yeast produced lactonic glycolipid that is decorated with a range of specific chemical moieties that are known to be chondrogenic and/or anti-inflammatory, 2) generate and characterize porous glycopolymer biomaterial scaffolds and 3) evaluate through in vitro investigations the chondrogenic and anti-inflammatory properties of these scaffolds to identify scaffolds warranting future in vivo evaluation. A key strategy in this work is the use of lactonic sophorolipids (LSLs) as building blocks since they are easily produced by fermentations in high yields (300 g/L). Furthermore, LSLs are amenable to a wide range of selective modification reactions both prior to or after polymerization that provides a platform for bioresorbable biomaterials whose structure and, therefore, functional properties, can be "tuned" as required. High school, undergraduate and Ph.D. students will be organized into teams in order to: i) provide mentoring opportunities between students at different levels and ii) to simulate today's workplace that increasingly utilizes interdisciplinary teams to solve complex problems. In this way, students in the program will gain an understanding and appreciation of high-level teamwork and communication between disciplines.