Optical monitoring of engineered tissues

工程组织的光学监测

• 批准号: 8286938
• 负责人: IRENE GEORGAKOUDI
• 金额: $ 32.26万
• 依托单位: TUFTS UNIVERSITY MEDFORD
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8286938
• 关键词: Adipose tissue; Animals; Biochemical; Biochemistry; Biocompatible Materials; Biological Markers; Bone Regeneration; Bone Tissue; Cell Differentiation process; Cell Survival; Cell physiology; Cells; Clinical; Collaborations; Collagen; Collection; Computer software; Data; Defect; Deposition; Detection; Development; Engineering; Equilibrium; Extracellular Matrix; Fatty acid glycerol esters; Fluorescence; Fracture; Funding; Goals; Growth; Histocompatibility Testing; Human; Image; Implant; In Vitro; Knowledge; Light; Mammary gland; Mesenchymal Stem Cells; Metabolic; Methods; Monitor; Morphology; Natural regeneration; Operative Surgical Procedures; Optical Methods; Optics; Osteoporosis; Outcome; Pathway interactions; Patients; Play; Process; Property; Proteins; Public Health; Reconstructive Surgical Procedures; Reporting; Research; Research Personnel; Resolution; Resources; Role; Sampling; Signal Transduction; Silk; Source; Staining method; Stains; Stem cells; Structure; System; Technology; Testing; Time; Tissue Engineering; Tissues; United States National Institutes of Health; Validation; Work; base; bone; bone engineering; cell growth; experience; functional status; imaging modality; implantation; in vivo; innovation; instrumentation; light scattering; mouse model; non-invasive monitor; novel; osteogenic; reconstruction; repaired; scaffold; soft tissue; spectroscopic imaging; stem cell biology; tissue regeneration; tissue repair; tool

Summary Our long-term goal is to develop non-invasive, optical technologies to monitor the functional development of engineered tissues in vitro and in vivo. The objective of this application is to develop optical biomarkers based on endogenous sources of optical contrast that obviate the use of exogenous stains and can be used to report quantitatively on the biochemical and structural composition of engineered tissues. The proposed studies focus on the characterization of adipose and bone engineered tissues developed from silk scaffolds seeded with human mesenchymal stem cells. The central hypothesis of the application is that linear and non-linear depth- resolved imaging methods based on the natural light scattering and fluorescence signatures of cell and matrix components of engineered tissues can be developed to report on the dynamic changes that occur prior to and following implantation of engineered tissues. Our hypothesis is based on preliminary evidence acquired from in vitro samples, which indicate that endogenous optical signals can be used to monitor changes in the biochemistry and morphology of differentiating stem cells, silk scaffolds and deposited collagen. The rationale for the proposed research is that the establishment of non-invasive methods that allow monitoring of the dynamic changes that occur within engineered tissues will play an essential role in the development and optimization of innovative, functional engineered tissue constructs. To achieve our goal we will characterize the endogenous fluorescence and light scattering signals from different cell and matrix components of engineered tissues developed in vitro (Aim 1). We will develop a system that will optimize acquisition of these optical signals from animals (Aim 2) and we will use these biomarkers to characterize non-invasively the integration of these engineered tissues in vivo following implantation either within a mammary fat pad or a cavarial bone defect mouse model (Aim 3). This will be the first time that dynamic monitoring of the biochemical and structural function of implanted engineered tissues is achieved in vivo using non-invasive means based on endogenous optical signals. This proposal is highly relevant to the improvement of public health as it will enable the efficient development of functional bone and adipose engineered tissues. Thus, millions of patients that undergo surgical procedures for the repair or reconstruction of such tissues will ultimately benefit from this work. Project Narrative This proposal is highly relevant to the improvement of public health as it will enable the efficient development of functional bone and adipose engineered tissues. Thus, millions of patients that undergo surgical procedures for the repair or reconstruction of such tissues will ultimately benefit from this work.

摘要 我们的长期目标是开发非侵入性的光学技术来监控功能的发展 体外和体内的工程化组织。本申请的目的是开发基于光学生物标记的 关于光学对比度的内源性来源，避免使用外源性染色并可用于报告 对工程化组织的生化和结构组成进行定量研究。建议的研究重点 种植真丝支架构建脂肪和骨组织工程组织的研究 人骨髓间充质干细胞。应用程序的中心假设是线性和非线性深度- 基于细胞和基质的自然光散射和荧光特征的分辨成像方法 可以开发工程组织的组件，以报告发生在 在植入工程组织后。我们的假设是基于从In 体外样本，这表明内源性光学信号可以用来监测 分化干细胞、丝素支架和沉积的胶原的生化和形态。其基本原理是 对于拟议的研究来说，建立非侵入性方法允许监测 发生在工程化组织内的动态变化将在发展和 优化创新的功能工程化组织结构。为了实现我们的目标，我们将描述 不同细胞和基质组分的内源性荧光和光散射信号 组织在体外发育(目标1)。我们将开发一个系统，以优化对这些光学设备的获取 来自动物的信号(目标2)，我们将使用这些生物标志物来非侵入性地表征 这些工程化组织植入乳房脂肪垫或腔静脉骨后在体内 缺陷小鼠模型(目的3)。这将是第一次对生化和生物化学进行动态监测 植入的工程组织的结构功能是在体内使用非侵入性手段实现的，基于 内源性光信号。 这一建议与改善公共卫生具有很高的相关性，因为它将使 功能性骨骼和脂肪工程组织。因此，数百万接受外科手术的患者 因为这种组织的修复或重建最终将从这项工作中受益。项目叙事 这一建议与改善公共卫生具有很高的相关性，因为它将使 功能性骨骼和脂肪工程组织。因此，数百万接受外科手术的患者 因为这种组织的修复或重建最终将从这项工作中受益。

项目成果

Young developmental age cardiac extracellular matrix promotes the expansion of neonatal cardiomyocytes in vitro.

年轻的发育年龄心脏外基质促进了新生儿心肌细胞在体外的扩张。

• DOI: 10.1016/j.actbio.2013.08.037
• 发表时间: 2014-01
• 期刊: ACTA BIOMATERIALIA
• 影响因子: 9.7
• 作者: Williams, C.;Quinn, K. P.;Georgakoudi, I.;Black, L. D., III
• 通讯作者: Black, L. D., III

Autocorrelation method for fractal analysis in nonrectangular image domains.

非矩形图像域分形分析的自相关方法。

• DOI: 10.1364/ol.38.004477
• 发表时间: 2013
• 期刊: Optics letters
• 影响因子: 3.6
• 作者: MacDonald,DouglasH;Hunter,Martin;Quinn,KyleP;Georgakoudi,Irene
• 通讯作者: Georgakoudi,Irene

Optical metrics of the extracellular matrix predict compositional and mechanical changes after myocardial infarction.

• DOI: 10.1038/srep35823
• 发表时间: 2016-11-07
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Quinn KP;Sullivan KE;Liu Z;Ballard Z;Siokatas C;Georgakoudi I;Black LD
• 通讯作者: Black LD

Non-destructive two-photon excited fluorescence imaging identifies early nodules in calcific aortic-valve disease.

• DOI: 10.1038/s41551-017-0152-3
• 发表时间: 2017-11
• 期刊: Nature biomedical engineering
• 影响因子: 28.1
• 作者: Baugh LM;Liu Z;Quinn KP;Osseiran S;Evans CL;Huggins GS;Hinds PW;Black LD 3rd;Georgakoudi I
• 通讯作者: Georgakoudi I

Membrane potential depolarization causes alterations in neuron arrangement and connectivity in cocultures.

• DOI: 10.1002/brb3.295
• 发表时间: 2015-01
• 期刊: BRAIN AND BEHAVIOR
• 影响因子: 3.1
• 作者: Oezkucur, Nurdan;Quinn, Kyle P.;Pang, Jin C.;Du, Chuang;Georgakoudi, Irene;Miller, Eric;Levin, Michael;Kaplan, David L.
• 通讯作者: Kaplan, David L.