Evaluation of Cartilage Tissue Engineering Strategies by IR Imaging

通过红外成像评估软骨组织工程策略

• 批准号: 9326141
• 负责人: Nancy Pleshko
• 金额: $ 30.5万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9326141
• 关键词: Address; Alpha Cell; Animal Model; Area; Biochemical; Biological Models; Biomechanics; Biopsy; Cartilage; Cell Count; Chondrocytes; Clinical; Clinical assessments; Collagen; Data; Defect; Development; Engineering; Evaluation; Exhibits; Family suidae; Fiber Optics; Functional disorder; Funding; Growth Factor; Harvest; Histologic; Human; Hyaluronic Acid; Image; Implant; In Vitro; Individual; Least-Squares Analysis; Magnetic Resonance Imaging; Mechanics; Methods; Miniature Swine; Modality; Modeling; Modulus; Molecular; Molecular Profiling; Molecular Structure; Monitor; Musculoskeletal; Near-Infrared Spectroscopy; Operative Surgical Procedures; Optical Methods; Outcome; Play; Production; Property; Proteoglycan; Protocols documentation; Regenerative Medicine; Role; Series; Spectroscopy, Fourier Transform Infrared; Techniques; Technology; Testing; Therapeutic; Thick; Time; Tissue Engineering; Tissues; Translating; Translations; Water; Work; X-Ray Computed Tomography; base; cartilage repair; cartilaginous; cell type; clinical development; clinical predictors; clinically relevant; design; implantation; in vivo; laboratory experiment; mechanical properties; microCT; mimetics; minimally invasive; novel; preimplantation; repaired; scaffold; subchondral bone; success; technique development; tissue regeneration; tissue repair

Summary: In spite of progress in understanding the pathophysiology of OA, there remain no definitive non-surgical treatment options. Further, tissue engineering strategies designed to produce cartilage-mimetic materials have seen only limited success; a significant impediment is the inability to fully assess the molecular structure of developing tissue such that optimal constructs for implantation can be identified. Recently, we demonstrated that the technique of non-destructive near infrared spectroscopy (NIRS) analysis can be utilized to assess the primary molecular components of native and engineered cartilage. NIRS data correlates strongly to water and matrix content (collagen and proteoglycan) in these tissues, and to mechanical properties. Having validated the NIR technology for cartilage assessment, we propose to extend our studies to address an important emerging area of musculoskeletal tissue engineering, identification of individual constructs suitable for clinical implantation. These studies are based on the principle that increases in construct maturation prior to implantation can be utilized to predict in vivo success. We hypothesize that maturation of the cartilaginous matrix can be monitored by NIRS, and that the spectral data can be used as a predictor of clinical success. We will address this in a series of in vitro and in vivo studies that evaluate construct development using NIRS analysis. A cell-seeded hyaluronic acid (HA) scaffold, previously shown to be effective at promoting matrix production and the development of functional material properties, will serve as the model system for implantation into a porcine model of cartilage repair. The proposed NIRS technology would establish a novel, non-destructive modality for pre-implantation evaluation of developing engineered tissues for clinical implantation. There are currently no minimally-invasive methods available for the clinical assessment of cartilage repair tissue maturation based on molecular signatures. The development of clinically-relevant optical methods to evaluate full-depth composition of tissues in a large animal model will provide a strong underpinning for translation of this technique into the clinical setting. Such analyses would also represent a fundamentally new and powerful approach for evaluating and guiding cartilage therapeutics. The possibility of one non-destructive modality that can be used in vitro during laboratory experiments of developing tissues to assess composition and identify constructs for implantation, as well as after the constructs are implanted clinically, would indeed be a powerful technique that could play a central role in the regenerative medicine field.

概括： 尽管对 OA 病理生理学的了解取得了进展，但仍然没有明确的非手术治疗方法 治疗方案。此外，旨在生产软骨模拟材料的组织工程策略已经 只取得了有限的成功；一个重大障碍是无法充分评估分子结构 发育组织，以便可以确定植入的最佳结构。最近，我们展示了 无损近红外光谱（NIRS）分析技术可用于评估 天然和工程软骨的主要分子成分。 NIRS 数据与水和 这些组织中的基质含量（胶原蛋白和蛋白多糖）以及机械性能。经验证后 用于软骨评估的近红外技术，我们建议扩展我们的研究以解决一个重要的新兴问题 肌肉骨骼组织工程领域，识别适合临床的个体结构 植入。这些研究基于这样的原理：在构建体成熟之前增加 植入可用于预测体内成功。我们假设软骨的成熟 矩阵可以通过 NIRS 进行监测，并且光谱数据可以用作临床成功的预测因子。我们 将在一系列使用 NIRS 评估构建体开发的体外和体内研究中解决这个问题 分析。细胞接种的透明质酸 (HA) 支架，先前已被证明可有效促进基质 功能材料特性的生产和开发，将作为模型系统 植入猪软骨修复模型。 拟议的 NIRS 技术将为植入前建立一种新颖的非破坏性模式 评估开发用于临床植入的工程组织。目前尚无微创 基于分子水平的软骨修复组织成熟度临床评估方法 签名。开发临床相关光学方法来评估组织的全面深度组成 在大型动物模型中的研究将为该技术转化为临床提供强有力的基础 环境。此类分析也将代表一种全新且强大的方法来评估和 指导软骨治疗。一种可在体外使用的非破坏性方式的可能性 发育组织的实验室实验，以评估成分并确定植入结构，例如 在将结构植入临床后，这确实是一种强大的技术，可以发挥 在再生医学领域发挥核心作用。