Depsipeptides as Tissue Engineering Scaffolds

非技术性：该奖项由材料研究部的生物材料项目授予德克萨斯大学奥斯汀分校，旨在开发一种新型的自组装多肽水凝胶支架，具有生物兼容性、可降解性和以空间定义的方式结合细胞的独特优势。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该具有对活细胞具有粘附性和支持性、可被人体降解以及与活组织相容的特性。此外，这样的支架应该很容易加工成3D结构，这是在有活细胞存在的情况下进行的理想情况。该项目将开发一种由分子制备的新型水凝胶，称为脱脂肽。该奖项将研究这些小分子在使用聚焦超声构图时自发地自组装成自支撑水凝胶的过程。这些水凝胶有望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越来越多地被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质的生物学特征的支架。计划的教育和外展活动包括：1)开发一个以学习为中心的框架和教学模块；2)在校园内支持和指导UTeachEngineering文科硕士项目的生物材料领域；以及3)开发实践外展活动，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脱肽，也称为酯酰胺。该系统利用多肽的两个分子区域：疏水尾巴控制组装；以及亲水性脱脂多肽低聚物，赋予生物活性和降解性。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，从而产生一系列具有一系列可能的生物活性的分子。目前的建议旨在合成标准的精氨酸-甘氨酸-天冬氨酸序列的脱肽类似物，该序列是一种普遍存在的氨基酸基序，可与细胞整合素结合，介导细胞黏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生产图案化的、细胞负载的和组织工程化的结构。这项工作将开发一个独特的平台来探索用于组织工程的材料的合理设计，其中需要具有生物特异性的微结构和可降解材料。所提出的研究是独一无二的，因为它们为精确定义细胞和组织响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。这项提议的总体教育目标是开发一个以学习为中心的框架，包括专门针对生物材料教育的推广和教学模块，以及服务于高中生的实践推广活动。

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.