Electrochemically Guided Collagen Synthesis for Functional Tissue Engineering

用于功能组织工程的电化学引导胶原蛋白合成

• 批准号: 7587640
• 负责人: Ozan Akkus
• 金额: $ 14.57万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-26 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7587640
• 关键词: Affect; Amendment; Behavior; Binding; Biocompatible Materials; Biological Assay; Biological Factors; Biomechanics; Biomimetics; Blood Vessels; Body Fluids; Bone Marrow; Caliber; Cells; Collagen; Collagen Fibril; Collagen Type I; Condition; Connective Tissue; Cues; Data; Dermatan Sulfate; Development; Dimensions; Fiber; Fibronectins; Fostering; Gel; Genotype; Glutaral; Goals; Hand; In Vitro; Length; Ligaments; Measures; Mechanics; Mesenchymal Stem Cells; Methods; Molecular; Morphology; Nature; Pathway interactions; Pattern; Peptides; Phase; Phenotype; Phosphate Buffer; Play; Process; Property; Public Health; Range; Rattus; Role; Saline; Shapes; Simulate; Site; Skin; Solutions; Stem cells; Tenascin; Tendon structure; Testing; Tissue Engineering; Tissues; Tubular formation; Weight-Bearing state; adult stem cell; analog; base; biomaterial compatibility; bone; clinically significant; concept; crosslink; decorin; density; desire; electric field; genipin; improved; novel; pH gradient; physical property; progenitor; prospective; repaired; research study; scaffold; size; synthetic construct; three dimensional structure

DESCRIPTION (provided by applicant): Collagen plays a central role as a biomaterial and as a scaffold in the regenerative tissue replacement strategies. Existing synthetic analogs of collagen have extremely poor biomechanical properties in comparison to the tissues they are targeted to replace due, in part, to the lack of orientation in hierarchical orders above the level of fibers. The overall goal of the proposed study is to demonstrate the feasibility of a novel biomechanically competent collagenous tissue engineering scaffold fabricated by: 1) an unconventional electrochemical process to attain an unprecedented level of molecular alignment and molecular packing density persistent across multiple 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 elucidate the mechanisms by which collagen solutions achieve long-range order under the effect of weak currents applied to directly to the solutions. The effects of pH gradient electric current amplitude and collagen concentration on the hierarchical organization of collagen will be investigated to optimize the synthetic process. The strength of resulting oriented collagen gels will be improved by identifying the appropriate type and concentration of crosslinking amongst genipin and glutaraldehyde. {The D-banding pattern and collagen fibril diameter will be improved by modulating the phosphate buffered saline treatment conditions.} The viscoelastic properties of oriented constructs will be modified 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 by macroscale mechanical tests and compared to those of rat tendon, a reference natural tissue. {Phase 2 is going to assess the differentiation of bone marrow derived mesenchymal stem cell progenitors on this material towards tenocytic lineage and foster this differentiation pathway by the mechanical cue.} Overall, the proposed study will: a) optimize the fabrication process variables of a novel fabrication method to obtain highly oriented tendon-mimicking constructs, and, b) assess the feasibility of the material as a tissue engineering scaffold by investigating phenotypic and genotypic behavior of bone marrow derived stem-cell progenitors seeded within the three-dimensional structures consisting of multiple collagenous bundles. A biomaterial of this nature may play a key role in creating strategies towards replacement of load bearing connective tissues such as tendons, ligaments, bones and vascular walls provided that the current study proves its feasibility. PUBLIC HEALTH RELEVANCE: The overall goal of the proposed study is to demonstrate the feasibility of a novel collagenous tissue engineering scaffold with mechanical properties converging those of tendon or ligaments. The study will assess the promise of this novel material by investigating whether adult stem cells seeded on this material differentiate to act like tendon cells.

描述（由申请人提供）：胶原蛋白作为生物材料和再生组织替代策略的脚手架起着核心作用。与它们针对的组织相比，胶原蛋白的现有合成类似物具有极低的生物力学特性，部分原因是由于纤维水平以上的层次阶层缺乏方向。拟议的研究的总体目标是证明一种新型生物力学能力的胶原组织工程脚手架的可行性：1）通过以下方面制造的脚手架：1）一个非常规的电化学过程，以实现分子比对的前所未有的分子对齐和分子堆积密度的跨多个级别的结构性质量层次的层次，并具有分子构成的层次，并具有结构性质量层次，并持续到结构性高位。 decorin类链接分子。拟议的研究的第1阶段将阐明胶原蛋白溶液在直接应用于溶液的弱电流的影响下实现远距离顺序的机制。将研究pH梯度电流振幅和胶原蛋白浓度对胶原蛋白分层组织的影响，以优化合成过程。通过鉴定Genipin和戊二醛之间的适当类型和浓度，可以提高产生的定向胶原蛋白凝胶的强度。 {通过调节磷酸盐缓冲盐水处理条件，将改善D带模式和胶原蛋白原纤维直径。}}定向构建体的粘弹性特性将通过连接到肽基序的硫酸皮肤基序中的DecorIn Mimip进行修饰，这些硫酸属硫酸盐与肽基序相结合，这些硫酸属型与I型胶原型胶原型结合到I胶原型胶原型。所得合成构建体的机械性能将通过宏观机械测试评估，并将其与参考天然组织大鼠肌腱的机械性能进行比较。 {第2阶段将评估该材料上骨髓的差异化，从而通过机械提示来促进养育养生谱系并促进这种分化途径。}总体而言，拟议的研究将：a）优化：a）优化新型制造方法的制造方法，以获取高度构造的材料，并评估了质子的构造，并评估了FERTON的构造，并且是FERTON的构造，并且是FERTON的构造，并且是fenton for的构造，并且是FERTON的构造。通过研究骨髓的表型和基因型行为，这些骨髓衍生的干细胞祖细胞在由多个胶原束组成的三维结构中播种。这种性质的生物材料可能在建立策略来替代轴承结缔组织（例如肌腱，韧带，骨骼和血管壁）方面起关键作用，但前台研究证明其可行性。 公共卫生相关性：拟议的研究的总体目标是证明具有机械性能的新型胶原组织工程支架的可行性，并融合了肌腱或韧带的机械性能。该研究将通过研究是否在该材料上播种的成年干细胞来评估这种新型材料的承诺，从而像肌腱细胞一样起作用。