Bridging the Gap between Nano and Macroscale Hierarchies in Collagen Assembly

弥合胶原蛋白组装中纳米级和宏观级层次之间的差距

• 批准号: 0754442
• 负责人: Alyssa Panitch
• 金额: $ 24万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0754442&HistoricalAwards=false
• 关键词: Bridging; Gap; between; Nano; Macroscale

CBET-0754442AkkusCollagen plays a central role as a biomaterial and as a scaffold in the regenerative tissue replacement strategies. Surgeries of load bearing tissues such as tendons and ligaments are occurring by hundreds of thousands annually and existing synthetic analogs of collagen have extremely poor biomechanical properties in comparison to the tissues they are targeted to replace. This shortcoming is due, in part, to the lack of orientation in hierarchical orders above the level of fibers. This project will improve the strength and viscoelasticity of synthetic collagenous constructs to match those of natural counterparts by: a) an unconventional electrochemical process to attain an unprecedented level of molecular alignment and molecular packing density persistent across all levels of structural hierarchies, and, 2) the control of interfibrillar attachment by use of a biomimetic decorin-like linkage molecule. Phase 1 of proposed studies will optimize the mechanical strength and stiffness of the construct by elucidating the mechanisms by which collagen solutions achieve long-range order under the effect of weak currents applied directly to the solutions. The effects of electric current amplitude and collagen concentration on the hierarchical organization of collagen will be investigated to optimize the synthesis process. The strength of resulting oriented collagen gels will be improved by identifying the appropriate type and concentration of crosslinking amongst glutaraldehyde, genipin, nordihydroguaiaretic acid (NDGA) or ribose. Phase 2 will modulate the viscoelastic properties of oriented and crosslinked gels by decorin mimics consisting of dermatan sulfate attached to peptide motifs which selectively bind to type I collagen molecules. Mechanical properties of resulting synthetic constructs will be assessed at the bundle and the fiber levels by macroscale mechanical tests and atomic force microscopy, respectively, and compared to those of rat tendon, a reference natural tissue. The third phase is going to assess the phenotypic and genotypic response of tendon fibroblasts seeded in three-dimensional networks of the oriented collagenous construct in vitro, and, by assessing the non-enzymatic and enzymatic degradation rates of constructs in vitro. The project will include the outreach component of familiarizing the minority middle-school student population with the emerging field of biomedical engineering. This aim will be attained by a summer activity during which students will conduct hands-on projects in the area of biomedical engineering through coordination with the Minority Engineering Program at Purdue University. Broader impacts will be further strengthened by creation of a laboratory module in an undergraduate biomechanics/biomaterials laboratory by incorporating outcomes of the proposed research and by way of accommodating 9 undergraduates for summer research during the course of the project through Summer Undergraduate Fellowship program (SURF) at Purdue. In the overall, the proposed study will develop a novel fabrication process towards the design of a new biomaterial which may play a key role in creating strategies towards replacement of tissues such as tendons, ligaments, skin, cornea and vascular walls.

CBET-0754442 Akkus胶原蛋白在再生组织替代策略中作为生物材料和支架发挥着核心作用。 承重组织如肌腱和韧带的表面置换每年发生数十万次，现有的胶原蛋白合成类似物与它们靶向置换的组织相比具有极差的生物力学性质。这种缺点部分是由于在纤维水平以上的层次顺序中缺乏取向。 该项目将通过以下方式改善合成胶原结构的强度和粘弹性，以与天然胶原结构相匹配：a）非常规电化学过程，以获得前所未有的分子排列水平和在所有结构层次中持续存在的分子堆积密度，以及2）通过使用仿生核心蛋白聚糖样连接分子控制纤维间附着。 拟定研究的第1阶段将通过阐明胶原蛋白溶液在直接施加于溶液的弱电流作用下实现长程有序的机制来优化结构的机械强度和刚度。 研究了电流幅值和胶原浓度对胶原分级结构的影响，以优化合成工艺。 通过确定戊二醛、京尼平、去甲二氢愈创木酸（NDGA）或核糖之间交联的适当类型和浓度，将提高所得定向胶原凝胶的强度。 第2阶段将通过核心蛋白聚糖模拟物调节定向和交联凝胶的粘弹性，核心蛋白聚糖模拟物由硫酸皮肤素连接到选择性结合I型胶原分子的肽基序组成。将通过宏观力学测试和原子力显微镜分别在束和纤维水平评估所得合成结构的机械性能，并与大鼠肌腱（参考天然组织）的机械性能进行比较。 第三阶段将评估肌腱成纤维细胞的表型和基因型反应接种在三维网络的定向胶原结构在体外，并通过评估非酶和酶降解率的结构在体外。 该项目将包括外联部分，使少数族裔中学生熟悉生物医学工程这一新兴领域。这一目标将通过暑期活动实现，在此期间，学生将通过与普渡大学少数民族工程项目的协调，在生物医学工程领域进行实践项目。 更广泛的影响将通过在本科生生物力学/生物材料实验室创建一个实验室模块来进一步加强，该模块将纳入拟议研究的成果，并通过普渡大学夏季本科生奖学金计划（SURF）在项目过程中容纳9名本科生进行夏季研究。总的来说，拟议的研究将开发一种新的制造工艺，用于设计一种新的生物材料，这种生物材料可能在制定肌腱、韧带、皮肤、角膜和血管壁等组织置换策略方面发挥关键作用。