Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model

用于大型动物模型半月板损伤修复的生物活性可注射细胞支架

基本信息

批准号：
10586596
负责人：
Chathuraka Teekshana Jayasuriya
金额：
$ 28.2万
依托单位：
RHODE ISLAND HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-04 至 2028-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10586596
关键词：
Affect Animal Model Animals Arthritis Attenuated Behavior Biocompatible Materials Biological Markers Biological Products Biological Response Modifier Therapy Cartilage Cells Cellular Structures Chemotactic Factors Chondrogenesis Collagen Collagen Fiber Complex Control Animal Data Degenerative polyarthritis Development Dose Effectiveness Evaluation Exhibits Extracellular Matrix Fast Green Fibrin Fibrinogen Fibrocartilages Flow Cytometry Gait Gel Gene Proteins Goals Green Fluorescent Proteins Histologic Histology Histopathology Human Hydrogels Image Injectable Injury Knee Knee Injuries Knee joint Knowledge Laboratories Magnetic Resonance Imaging Measures Mechanics Medial meniscus structure Mediator Meniscus structure of joint Mesenchymal Stem Cells Microscopic Miniature Swine Mission Modeling National Institute of Arthritis, and Musculoskeletal, and Skin Diseases Nature Organ Culture Techniques Organism Orthopedics Outcome Assessment Outcome Measure Patients Plasma Prevention Production Proteoglycan Public Health Rattus Reporting Research Research Design Risk Factors Severities Sirius Red F3B Site Stains Stromal Cell-Derived Factor 1 Surgical sutures Synovial Fluid Synovial Membrane Technology Testing Thrombin Time Tissue Model Tissues Translating Translations Traumatic Arthropathy United States National Institutes of Health Urine Visualization articular cartilage base biomaterial compatibility chemokine clinical translation clinically relevant disability efficacy evaluation experimental group healing improved in vivo evaluation injury and repair innovation lymph nodes meniscal tear meniscus injury musculoskeletal injury novel polarized light porcine model pre-clinical prevent repaired response scaffold small molecule stem cells success treatment response

项目摘要

SUMMARY ABSTRACT Meniscal tearing is a significant risk factor for the development of posttraumatic osteoarthritis (PTOA). The long- term goal of this project is to develop an innovative biologic therapy to improve meniscus tear healing for the prevention of PTOA. Our laboratory has demonstrated the efficacy of utilizing cartilage-derived progenitor cells (CPCs) to stimulate healing of meniscal tears in a small animal model. In efforts to translate our success in small animals to a clinically relevant large animal model, we will optimize and implement a bioactive tear interfacing fibrin hydrogel (FibroGel) that is laden with CPCs and infused with the chemokine Stromal Cell Derived Factor- 1 (SDF-1) and the small molecule Kartogenin (KGN), which collectively increases CPC retention at the tear site and increases their chondrogenic matrix synthesis, respectively. The objectives of the proposed study are: To optimize FibroGel as a novel biologic therapy for meniscus tear repair; (2) To determine its efficacy for stimulating tear reunification and reduction of PTOA severity; and (3) To collect biocompatibility data throughout the study to aid in clinical translation of this technology. There are three independent specific aims: (I) Optimize cellular and bioactive components of FibroGel to produce robust fibrocartilage matrix re-synthesis to bridge and reunify meniscus tears; (II) Evaluate the efficacy of using FibroGel for improving meniscal fibrocartilage healing in a preclinical large animal model; and (III) Determine the efficacy of FibroGel-augmented meniscus repair in attenuating PTOA in the knee. The research design will employ a meniscus tissue explant model to optimize FibroGel in order to maximize cell retention and chondrogenic matrix re-synthesis at the tear site, as well as increase the strength of tissue reintegration/reunion at the tear site. A porcine model of meniscal injury will be used to examine the short- and long-term efficacy and biocompatibility of FibroGel. Outcome assessments will include evaluation of meniscus tear healing, evaluation of PTOA severity as determined by biomarker analysis, gait asymmetry analysis, and macroscopic/microscopic assessment of the articular cartilage and synovium following FibroGel treatment. Successful completion will have a positive impact by facilitating the development and translation of a new strategy to stimulate meniscus injury repair through the use of cellular biologics. This project is relevant to the mission of NIAMS because it seeks to find innovative ways to treat musculoskeletal injuries and prevent arthritis.

摘要摘要半月板撕裂是发生创伤后骨关节炎（PTOA）的重要危险因素。长- 该项目的长期目标是开发一种创新的生物疗法，以改善半月板撕裂的愈合预防PTOA。我们的实验室已经证明了利用软骨源性祖细胞的功效（CPC）刺激小动物模型中半月板撕裂的愈合。努力将我们的成功转化为小事动物到临床相关的大型动物模型，我们将优化和实施生物活性泪液接口纤维蛋白水凝胶 (FibroGel) 充满 CPC 并注入趋化因子基质细胞衍生因子 - 1 (SDF-1) 和小分子 Kartogenin (KGN)，共同增加 CPC 在撕裂部位的保留并分别增加其软骨基质合成。拟议研究的目标是：优化 FibroGel 作为半月板撕裂修复的新型生物疗法； (2) 确定其功效刺激泪液重新统一并降低 PTOA 严重程度； (3) 收集整个过程中的生物相容性数据该研究旨在帮助这项技术的临床转化。存在三个独立的具体目标：（一）优化 FibroGel 的细胞和生物活性成分可产生强大的纤维软骨基质再合成，以桥接和重新统一半月板撕裂；（二）评估使用FibroGel改善半月板纤维软骨愈合的功效在临床前大型动物模型中； (III) 确定 FibroGel 增强半月板修复术的功效减弱膝关节中的 PTOA。研究设计将采用半月板组织外植体模型来优化 FibroGel 可以最大程度地保留撕裂部位的细胞并促进软骨基质的重新合成，以及增加撕裂部位组织重新整合/团聚的强度。猪半月板损伤模型用于检查 FibroGel 的短期和长期功效以及生物相容性。结果评估将包括半月板撕裂愈合的评估、通过生物标志物分析确定的 PTOA 严重程度的评估、步态不对称分析以及关节软骨和滑膜的宏观/微观评估 FibroGel 治疗后。顺利完成将对促进发展产生积极影响并转化了一种通过使用细胞生物制剂刺激半月板损伤修复的新策略。这该项目与 NIAMS 的使命相关，因为它寻求寻找治疗肌肉骨骼疾病的创新方法受伤并预防关节炎。