Development of Injectable Super-Lubricious Microgels for Sustained Release of Platelet-Rich Plasma to Treat Post-Traumatic Osteoarthritis

开发可注射的超润滑微凝胶，用于持续释放富含血小板的血浆以治疗创伤后骨关节炎

• 批准号: 10659591
• 负责人: MUHAMMAD FAROOQ RAI
• 金额: $ 58.48万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-10 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10659591
• 关键词: Acceleration; Affect; American; Animal Model; Anti-Inflammatory Agents; Arthritis; Autophagocytosis; Biochemical; Biological Assay; Blood Platelets; Buffers; Cartilage; Cattle; Cell Survival; Cells; Chondrocytes; Chronic; Circular Dichroism; Clinic; Clinical Treatment; Complex; Complex Mixtures; Confocal Microscopy; Degenerative polyarthritis; Development; Disease; Dopamine; Effectiveness; Encapsulated; Environment; Fluorescence; Flushing; Fractionation; Friction; Gait; Gel; Gene Expression; Genes; Health; Homeostasis; Hour; Human; Hydrogels; In Situ; In Vitro; Individual; Inflammation; Inflammatory; Inflammatory Response; Injectable; Injections; Injury; Intervention; Joint Instability; Joints; Kinetics; Knee; Knee Injuries; Knee Osteoarthritis; Knee joint; Lipids; Longevity; Lymphatic System; Measures; Mechanics; Medial meniscus structure; Mediator; Methacrylates; Methods; Microfluidics; Microscopy; Microspheres; Modeling; Mus; Natural regeneration; Oral; Outcome; Pain; Pain Measurement; Pathway interactions; Patients; Performance; Periodicity; Persons; Pharmaceutical Preparations; Plasma; Play; Polyethylene Glycols; Preparation; Process; Production; Proliferating; Proteins; Proteomics; Publishing; Replacement Arthroplasty; Rheology; Role; Scanning Electron Microscopy; Sclerosis; Societies; Spectrum Analysis; Spinal; Synovial Fluid; Synovitis; System; Systems Analysis; Techniques; Testing; Therapeutic Effect; Time; Transcript; Traumatic Arthropathy; United States; Vertebral column; arthropathies; articular cartilage; cartilage degradation; cartilage regeneration; economic cost; effectiveness evaluation; end stage disease; fabrication; functional outcomes; gait examination; immunotoxicity; improved; in vivo evaluation; knee replacement arthroplasty; lipidomics; macromolecule; mechanical properties; methacrylamide; mouse model; osteochondral tissue; palliative; particle; prevent; recruit; regenerative; response; restoration; socioeconomics; subchondral bone; tissue regeneration; transcriptome; transcriptome sequencing

Project summary Post-traumatic osteoarthritis (PTOA) is a painful, debilitating and expensive joint disease that conservatively impacts 5.6 million people at any time in the United States. Currently available clinical treatments are mostly palliative and fail to suppress cartilage degeneration or synovial inflammation or to promote tissue regeneration. Consequently, osteoarthritis progresses to an end-stage disease where total joint replacement is the only answer. Our aim is to provide an injectable solution for the treatment of PTOA, through the fabrication of super- lubricious microspheres loaded with platelet-rich plasma (PRP), which is blood plasma that has been spun down to concentrate the platelet component. These platelets contain more than 300 bioactive molecules that play critical roles in controlling and resolving inflammation, while also stimulating cells within the joint to proliferate and regenerate tissues such as articular cartilage. Unfortunately, direct injection of PRP into the knee joint has shown inconsistent efficacy in the clinic, mainly because the harsh environment within the osteoarthritic knee rapidly breaks down and destroys the bioactive molecules rendering them useless for therapeutic effect. Therefore, we propose to fabricate lubricious injectable polyethylene glycol (PEG) microspheres for injection into the intra-articular knee space that cannot be cleared by the body with the synovial fluid turnover. We will evaluate the incorporation and release as well as bioactivity and immunotoxicity of PRP from the hydrogel system, through both quantification of specific proteins released over time and in vitro cellular response studies, respectively. Finally, PRP-loaded microspheres will be used in a mouse model of knee injury and osteoarthritis to determine the ability for our system to i) modify the intracapsular inflammatory state, ii) stop cartilage degeneration, iii) promote new cartilage formation and, iii) restore joint homeostasis.

项目摘要 创伤后骨关节炎（PTOA）是一种疼痛，衰弱和昂贵的关节疾病， 影响着美国560万人目前的临床治疗方法大多是 姑息性的，不能抑制软骨退化或滑膜炎症或促进组织再生。 因此，骨关节炎进展为终末期疾病，其中全关节置换术是唯一的治疗方法。 答案我们的目标是提供一种可注射的解决方案，用于治疗PTOA，通过制造超级， 一种润滑的微球，装有富含血小板的血浆（PRP），这是一种离心沉降的血浆 以浓缩血小板成分。这些血小板含有300多种生物活性分子， 在控制和解决炎症方面起着关键作用，同时也刺激关节内的细胞增殖 并再生组织如关节软骨。不幸的是，将PRP直接注射到膝关节中， 在临床上表现出不一致的疗效，主要是因为骨关节炎膝关节内的恶劣环境 快速分解并破坏生物活性分子，使其对治疗效果无用。 因此，我们建议制备润滑的可注射聚乙二醇（PEG）微球，用于注射到 关节内膝关节间隙不能被身体清除与滑液周转。我们将评估 PRP从水凝胶系统的掺入和释放以及生物活性和免疫毒性，通过 分别对随时间释放的特定蛋白质进行定量和体外细胞反应研究。 最后，将载PRP的微球用于膝关节损伤和骨关节炎的小鼠模型，以确定 我们的系统能够i）改变囊内炎症状态，ii）阻止软骨退化，iii） 促进新的软骨形成和，iii）恢复关节稳态。