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

来自具有软骨形成和抗炎特性的天然糖脂的功能性糖聚合物组织工程支架

• 批准号: 1508422
• 负责人: Richard Gross
• 金额: $ 39万
• 依托单位: Rensselaer Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1508422&HistoricalAwards=false
• 关键词: Functional; Glycopolymer; Tissue; Engineering; Scaffolds

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.

非技术：该奖项授予伦斯勒理工学院，旨在开发一种有效的策略来修复与骨关节炎相关的软骨缺陷，同时还治疗通常导致关节恶化的慢性炎症。目前临床上对软骨缺损的治疗方法可以暂时恢复关节功能。然而，这些方法不能治疗慢性炎症循环，这种循环导致与骨关节炎相关的组织退化。将开发一种组织工程支架，不仅可以恢复局部受损的软骨功能，而且随着支架的降解，抗炎分子可以持续释放到周围的润滑滑液中。为了实现这一目标，PI将进一步开发一系列独特的生物材料，这些材料来自酵母细胞产生的天然构建块，由脂肪酸和糖残基组成。通过“绿色化学”方法制备的聚合物将进行调整，使其具有组织工程支架所需的生物学特性。此外，生物材料在发挥其功能后，会被水解性降解为安全分子。参加这一课程的博士、本科生和高中生将在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方面获得至关重要的技能。学生将在团队中工作，学习批判性沟通技能，并将培养对跨学科研究问题的深刻理解。技术：这项拟议的研究试图开发一种组织工程学策略，在修复与骨关节炎相关的软骨缺陷的同时，还治疗通常导致关节恶化的慢性炎症。拟议研究中的目标是：1)开发通过酵母产生的乳酸糖脂的开环歧化聚合(ROMP)合成的糖共聚物文库，该文库中装饰有一系列已知的成软骨和/或抗炎的特定化学部分；2)制备并表征多孔糖共聚物生物材料支架；3)通过体外研究评估这些支架的成软骨和抗炎性能，以确定未来有必要进行体内评估的支架。这项工作中的一个关键策略是使用乳酸苦参脂脂(LSL)作为构建块，因为它们很容易通过发酵高产率(300g/L)生产。此外，LSL在聚合之前或聚合后都可以进行广泛的选择性修饰反应，这为生物可吸收生物材料提供了一个平台，其结构和功能特性可以根据需要进行“调整”。高中生、本科生和博士生将被组织成小组，以便：i)在不同级别的学生之间提供指导机会；ii)模拟当今越来越多地利用跨学科团队来解决复杂问题的工作场所。通过这种方式，该项目的学生将获得对高水平团队合作和学科间沟通的理解和欣赏。