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
基本信息
- 批准号:7587640
- 负责人:
- 金额:$ 14.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AffectAmendmentBehaviorBindingBiocompatible MaterialsBiological AssayBiological FactorsBiomechanicsBiomimeticsBlood VesselsBody FluidsBone MarrowCaliberCellsCollagenCollagen FibrilCollagen Type IConditionConnective TissueCuesDataDermatan SulfateDevelopmentDimensionsFiberFibronectinsFosteringGelGenotypeGlutaralGoalsHandIn VitroLengthLigamentsMeasuresMechanicsMesenchymal Stem CellsMethodsMolecularMorphologyNaturePathway interactionsPatternPeptidesPhasePhenotypePhosphate BufferPlayProcessPropertyPublic HealthRangeRattusRoleSalineShapesSimulateSiteSkinSolutionsStem cellsTenascinTendon structureTestingTissue EngineeringTissuesTubular formationWeight-Bearing stateadult stem cellanalogbasebiomaterial compatibilityboneclinically significantconceptcrosslinkdecorindensitydesireelectric fieldgenipinimprovednovelpH gradientphysical propertyprogenitorprospectiverepairedresearch studyscaffoldsizesynthetic constructthree dimensional structure
项目摘要
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(申请人提供):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。现有的合成胶原蛋白类似物的生物力学性能与它们要替代的组织相比非常差,部分原因是在纤维水平上缺乏层级顺序的取向。这项研究的总体目标是证明一种新型的具有生物力学性能的胶原组织工程支架的可行性:1)通过非传统的电化学过程获得前所未有的水平的分子排列和分子堆积密度,跨越多个层次的结构层次;以及2)通过仿生核心蛋白粘附素连接分子来控制纤维间附着。拟议研究的第一阶段将阐明胶原蛋白溶液在弱电流直接作用下实现长程有序化的机制。研究了pH梯度、电流幅值和胶原浓度对胶原蛋白分级结构的影响,以优化合成工艺。通过确定京尼平和戊二醛之间的适当类型和浓度的交联剂,将提高所得到的定向胶原凝胶的强度。{通过调节磷酸盐缓冲盐水处理条件,D-带模式和胶原纤维直径将得到改善。}定向结构的粘弹性将通过将硫酸皮肤素连接到多肽基序上的核心蛋白粘附素模拟物来改善,该模拟物选择性地结合到I型胶原分子上。合成结构的力学性能将通过宏观力学测试进行评估,并与大鼠肌腱进行比较,大鼠肌腱是一种参考的自然组织。{第二阶段将评估骨髓间充质干细胞前体细胞在该材料上向腱细胞系的分化,并通过机械线索促进这一分化途径。}总体而言,拟议的研究将:a)优化一种新的制造方法的制造工艺变量,以获得高度定向的肌腱仿制结构,以及b)通过研究种植在由多个胶原束组成的三维结构中的骨髓来源干细胞前体细胞的表型和基因行为,评估该材料作为组织工程支架的可行性。如果目前的研究证明其可行性,这种性质的生物材料可能在创造替代肌腱、韧带、骨骼和血管壁等承载结缔组织的策略方面发挥关键作用。
与公共卫生相关:拟议研究的总体目标是证明一种新型胶原组织工程支架的可行性,该支架具有与肌腱或韧带相同的力学性能。这项研究将通过研究种植在这种材料上的成体干细胞是否分化为肌腱细胞来评估这种新型材料的前景。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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Ozan Akkus其他文献
Ozan Akkus的其他文献
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Cartilage Repair by Condensed Mesenchymal Stem Cell Delivery via Collagen Fabric
通过胶原蛋白织物输送浓缩间充质干细胞来修复软骨
- 批准号:
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$ 14.57万 - 项目类别:
Tendon Tissue Engineering by Electrochemically Aligned Collagen Bioscaffolds
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9089701 - 财政年份:2015
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Tendon Tissue Engineering by Electrochemically Aligned Collagen Bioscaffolds
通过电化学排列胶原生物支架进行肌腱组织工程
- 批准号:
8835033 - 财政年份:2014
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Tendon Tissue Engineering by Electrochemically Aligned Collagen Bioscaffolds
通过电化学排列胶原生物支架进行肌腱组织工程
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8697319 - 财政年份:2014
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$ 14.57万 - 项目类别:
Tendon Tissue Engineering by Electrochemically Aligned Collagen Bioscaffolds
通过电化学排列胶原生物支架进行肌腱组织工程
- 批准号:
9247755 - 财政年份:2014
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Diagnosis of Crystal-Based Arthropathies via Raman Spectroscopy
通过拉曼光谱诊断晶体关节病
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8322612 - 财政年份:2011
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