Tissue-Engineered Constructs for Treatment of Intervertebral Disc Degeneration

用于治疗椎间盘退变的组织工程结构

• 批准号: 9173422
• 负责人: Harvey E. Smith
• 金额: --
• 依托单位: PHILADELPHIA VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-10-01 至 2019-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9173422
• 关键词: Academic Medical Centers; Activities of Daily Living; Address; Animal Model; Animals; Autologous; Basic Science; Biochemical; Biological Models; Biology; Biomechanics; Bone Marrow; Cell Survival; Cells; Cellular Infiltration; Cellular biology; Chondrocytes; Clinical; Defect; Deposition; Development; Engineering; Environment; Evaluation; Extracellular Matrix; Fiber; Foundations; Funding; Gel; Gene Expression Regulation; Goals; Growth; Harvest; Health; Height; Histologic; Human; Hyaluronic Acid; Hydrogels; Image; Imaging Techniques; Implant; In Vitro; Individual; Inflammation; Injury; Intervertebral disc structure; K-Series Research Career Programs; Laboratories; Lead; Magnetic Resonance Imaging; Maps; Measures; Mechanics; Mentors; Mentorship; Mesenchymal Stem Cells; Methodology; Methods; Modeling; Morbidity - disease rate; Motion; Musculoskeletal; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Outcome Measure; Pain; Pennsylvania; Phenotype; Philadelphia; Population; Pre-Clinical Model; Production; Property; Proteins; Recurrence; Research; Research Design; Research Methodology; Research Personnel; Risk; Scientist; Spine surgery; Staging; Stem cells; Structure; Surgeon; Therapeutic; Time; Tissue Engineering; Tissues; Translational Research; Translations; Treatment Efficacy; Vertebral column; Weight-Bearing state; Work; base; biophysical properties; career; cell type; clinical practice; density; economic cost; end stage disease; experience; implantation; in vitro Model; in vivo; intervertebral disk degeneration; loss of function; nanofiber; non-invasive imaging; novel therapeutics; nucleus pulposus; programs; repaired; research clinical testing; scaffold; soft tissue; tissue culture; translational study; treatment strategy

DESCRIPTION The objective of this project is to develop a tissue-engineered construct including an engineered nucleus pulposus and annulus fibrosus to treat defects of the annulus fibrosus (AF) and degenerative changes of the intervertebral disc (IVD). Three Specific Aims are pursued: " Specific Aim 1 will consist of establishing in vitro tissue engineered NP fabrication from rabbit and human NP and MSC cells in hyaluronic acid (HA)-based hydrogel constructs, and evaluation of cell viability, gene regulation, ECM production, and biomechanical properties as a function of gel biophysical properties, cell seeding density, and extended culture in a disc-like environment. " Specific Aim 2 will entail establishing and evaluating cellular infiltration and functional maturation engineered AF-like structures starting from rabbit and human AF and MSC seeded nanofibrous scaffolds in vitro. " Specific Aim 3 will combine the tissue-engineered NP and AF developed in Aims 1 and 2 to form a composite disc-like construct, and to then apply this construct to an in vivo rabbit disc model of total discectomy. Efficacy will be assesse via MRI T2 mapping and subsequent ex vivo analysis of motion segment mechanical, biochemical, and histologic properties. Research Design: This study will utilize in vitro tissue culture for Specific Aims 1-2; Specific Aim 3 will utilize a rabbit animal model and magnetic resonance imaging (MRI). Methodology: Specific Aims 1 and 2 are laboratory-based studies that will utilize in vitro tissue culture. Specific Aim 3 will be performed in vivo with a rabbit mdel for discectomy and tissue-engineered disc implantation with subsequent ex vivo MRI of the spine and tissue analysis. The primary study outcome measures for Specific Aims 1-3 are biochemical analysis of tissue culture and biomechanical analysis of tissue-engineered constructs. Additionally, Specific Aim 3 will utilize these same outcomes, as well as implement quantitative MRI T2 maps of the implanted tissue-engineered constructs with comparisons made to control (non-treated discectomy) and adjacent normal discs. Findings: n/a at this time. Clinical Relationships: The goal of this project is to develop tissue-engineered constructs to trea degenerative disc disease as well as to validate radiologic methods to noninvasively assess potential therapeutic treatments of degenerative disc disease. Impact/Significance: It is anticipated that the proposed study will offer an increased understanding of degenerative disc disease and potential novel therapeutic treatment to both reverse degenerative changes as well as decrease risk of recurrent disc herniation. Further, it will provide critical support for the applicant as he develops a research-intensive clinical practice in spine surgery at the Philadelphia VA Medical Center and the University of Pennsylvania.

描述 该项目的目的是开发一种组织工程的构建体，包括工程核和纤维纤维，以治疗环形纤维纤维（AF）的缺陷以及椎间盘（IVD）的退化变化。提出了三个特定目的：“具体目标1将包括建立透明质酸（HA）基于水凝胶（HA）的水凝胶构建体中的兔子，人NP和MSC细胞的体外组织NP制造，以及评估细胞活力，基因调节，ECM生产，ECM生产以及生物机械性能，并具有特定的生物体性，并具有特定的环境，并注意到了各种环境，并具有浓度的环境，并具有浓度的种子，并具有浓度的种子。需要在体外​​建立和评估细胞浸润和功能成熟的类似AF的结构。 “具体目标3将结合组织工程的NP和AIM 2中开发的AF，形成一个类似于复合盘的构建体，然后将该构建体应用于总椎间盘切除术的体内兔子盘模型中。将通过MRI T2映射和随后的动态群体进行机械性，研究型物质的培训。将其用于整体研究。目的1-2；特定目标将使用兔动物模型和磁共振成像（MRI）：特定的目标是基于实验室的研究，它将使用体外组织培养物3 1-3是组织培养的生化分析和组织工程结构的生物力学分析。调查结果：N/A此时。临床关系：该项目的目的是开发进行组织的构造来进行TREA退行性椎间盘疾病，并验证放射学方法，以无创评估退行性椎间盘疾病的潜在治疗治疗方法。影响/意义：预计拟议的研究将对退行性椎间盘疾病和潜在的新型治疗治疗提供更多的了解，从而反向退行性变化，并降低复发性椎间盘突出症的风险。此外，在申请人在费城弗吉尼亚州医学中心和宾夕法尼亚大学开发研究密集型脊柱手术的临床实践时，它将为申请人提供重要的支持。