Depsipeptides as Tissue Engineering Scaffolds

缩肽作为组织工程支架

• 批准号: 1609212
• 负责人: Laura Suggs
• 金额: $ 38.98万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2020-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1609212&HistoricalAwards=false
• 关键词: Depsipeptides; Tissue; Engineering; Scaffolds

Non-technical: This award by the Biomaterials program in the Division of Materials Research to the University of Texas at Austin is to develop a novel class of self-assembling, peptide-based hydrogel scaffolds with the unique advantages of biologic compatibility, degradability and the ability to incorporate cells in a spatially defined manner. This award is co-funded by BioMaPS funds in the Division of Materials Research, and the Biomedical Engineering program in the Division of Chemical, Bioengineering, Environmental, and Transport Systems. An ideal tissue engineering scaffold would possess the properties of being adhesive and supportive to living cells, degradable by the body and compatible with living tissues. Furthermore, such a scaffold should be easily processable into 3D configurations, and this is ideally performed in the presence of living cells. This project would develop a novel class of hydrogels prepared from molecules known as depsipeptides. This award will study the spontaneous self-assembly of these small molecules into self-supporting hydrogels when patterned using focused ultrasound. These hydrogels are expected to fulfill all of the requirements of an ideal tissue scaffold. The cell-interactive hydrogel scaffolds have increasingly been explored for use in tissue engineering and regenerative medicine, particularly those that can both self-assemble and mimic the biological features of structural proteins. The planned educational and outreach activities include: 1) development of a learning-centered framework with instructional modules; 2) support and mentor the UTeachEngineering Master of Arts program in the campus in the area of biomaterials; and 3) develop hands-on outreach activities to serve high school students.Technical: With this award, this researcher will study self-assembling depsipeptides, also known as ester amides. This system makes use of two molecular regions of the peptide: a hydrophobic tail to control assembly; and a hydrophilic depsipeptide oligomer which confers biologic activity and degradability. These molecules can self-assemble into different ordered structures including nanoparticles and fibrous, hydrogel scaffolds. The side chains can be varied among a wide range of chemical groups, resulting in a family of molecules with a host of possible bioactivities. The current proposal seeks to synthesize depsipeptide analogs of the canonical Arginine-Glycine-Aspartic acid sequence, an ubiquitous amino acid motif known to bind cell integrins to mediate cell adhesion and interaction with the extracellular matrix. Furthermore, due to the unique kinetics of this self-assembly, the project will utilize a focused ultrasound transducer to produce patterned, cell-laden and tissue engineered constructs. This work will develop a unique platform to explore the rational design of materials for applications in tissue engineering, where a microstructured and degradable material is needed with biologic specificity. The proposed studies are unique in that they offer a tailorable platform for the precise definition of cell and tissue responses, and the design strategy could be broadly applied for the development of other biomaterials. The overall educational goal of this proposal is to develop a learning-centered framework of outreach and instructional modules specifically geared around biomaterials education, and hands-on outreach activities to serve high school students.

非技术性：该奖项由德克萨斯大学奥斯汀分校材料研究部的生物材料项目授予，旨在开发一类新型的自组装肽基水凝胶支架，具有生物相容性，可降解性和以空间限定方式掺入细胞的能力的独特优势。该奖项由材料研究部的BioMaPS基金和化学，生物工程，环境和运输系统部的生物医学工程项目共同资助。理想的组织工程支架应具备对活细胞具有粘附和支持作用、可降解、与活组织相容等特性。此外，这样的支架应该容易加工成3D构型，并且这理想地在活细胞存在下进行。该项目将开发一种新型的水凝胶，由称为缩肽的分子制备。该奖项将研究这些小分子在使用聚焦超声进行图案化时自发自组装成自支撑水凝胶。预期这些水凝胶满足理想组织支架的所有要求。细胞相互作用的水凝胶支架已经越来越多地被探索用于组织工程和再生医学，特别是那些既可以自组装又可以模拟结构蛋白的生物学特征的支架。 计划的教育和推广活动包括：1）开发以学习为中心的教学模块框架; 2）在生物材料领域支持和指导校园内的UTeachEngineering文学硕士课程; 3）开发实践推广活动，为高中生服务。技术：有了这个奖项，这位研究人员将研究自组装缩肽，也被称为酯酰胺。 该系统利用肽的两个分子区域：控制组装的疏水性尾部;和赋予生物活性和降解性的亲水性缩肽寡聚体。 这些分子可以自组装成不同的有序结构，包括纳米颗粒和纤维状水凝胶支架。 侧链可以在广泛的化学基团中变化，从而产生具有许多可能的生物活性的分子家族。目前的建议试图合成经典精氨酸-甘氨酸-天冬氨酸序列的缩肽类似物，已知其是一种普遍存在的氨基酸基序，结合细胞整联蛋白以介导细胞粘附和与细胞外基质的相互作用。此外，由于这种自组装的独特动力学，该项目将利用聚焦超声换能器来产生图案化的、载有细胞的和组织工程化的结构。这项工作将开发一个独特的平台，以探索组织工程中应用的材料的合理设计，其中需要具有生物特异性的微结构和可降解材料。所提出的研究是独特的，因为它们为精确定义细胞和组织反应提供了一个可定制的平台，并且设计策略可以广泛应用于其他生物材料的开发。 该提案的总体教育目标是开发一个以学习为中心的外展框架和专门针对生物材料教育的教学模块，并为高中学生提供实践外展活动。