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CST6-mRNA activated matrices for efficient bone regeneration

CST6-mRNA 激活基质可实现高效骨再生

基本信息

批准号：
10456455
负责人：
Aliasger K Salem
金额：
$ 19.31万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-01 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10456455
关键词：
Aftercare Alkaline Phosphatase BMP2 gene Biocompatible Materials Biological Biomimetic Materials Bone Development Bone Marrow Bone Regeneration Bone Tissue CST6 gene Cell model Cells Chemicals Clinic Clinical Collagen Collagen Type I Core-Binding Factor Cystatins Cysteine Proteinase Inhibitors Cytoplasm DNA Defect Dentistry Dose Effectiveness Encapsulated Environment Enzyme-Linked Immunosorbent Assay Evaluation Failure Family Future Gelatinase B Gene Expression Profiling Genes Goals Growth Factor Histology Imaging Techniques Implant In Vitro Knowledge Left Lipids Lytic Lesion Marrow Mechanics Medicine Messenger RNA Modality Monitor Multiple Myeloma Mus Nodule Non-Viral Vector Nuclear Nucleic Acids Orthopedics Osteocalcin Osteoclasts Osteogenesis Patients Pilot Projects Plasmids Process Production Protease Inhibitor Proteins Protocols documentation RNA Rattus Recombinant Proteins Recombinants Regenerative Medicine Reverse Transcriptase Polymerase Chain Reaction Safety Sampling Sprague-Dawley Rats Stains Stromal Cells System Testing Therapeutic Time Tissue Engineering Torsion Transfection Translating Translations Vascular Endothelial Growth Factors Viral Vector angiogenesis base bone bone fracture repair bone healing bone scaffold cathepsin K chemical release collagen scaffold cost effective cytotoxicity dosage gait examination gene therapy immunogenicity implantation in vitro Model in vivo in vivo Model innovation macrophage microCT nanoparticle novel novel therapeutics osteoblast differentiation osteogenic particle plasmid DNA regeneration potential regenerative approach stem tartrate-resistant acid phosphatase tissue regeneration translational potential

项目摘要

Project Summary Bone regeneration is a carefully orchestrated dynamic process that involves several key biological players, including growth factors and cells. Bone tissue engineering aims to provide an environment that facilitates and augments the natural bone regeneration process. CST6 is a cysteine protease inhibitor that is highly expressed in multiple myeloma patient samples lacking any bone lytic lesion, compared to those samples with at least one bone lytic lesion. In vitro pilot studies show that CST6 (in the recombinant protein form) promotes osteoblast differentiation and inhibit osteoclast differentiation. CmRNA has the unique advantage of functioning entirely in the cytoplasm (avoiding the need for nuclear entry) thereby, leading to a targeted transient expression of desired proteins with immense potential to overcome the challenges that exist with protein and DNA based approaches. Specifically, this study aims to develop a biomaterial-based delivery system that releases cmRNA (CST6) to induce in vivo bone regeneration. Our aims are 1) to demonstrate that nanoparticle loaded cmRNA (CST6) can efficiently trigger osteogenic differentiation and inhibit osteoclast maturation and 2) to assess bone regeneration efficacy of a collagen scaffold that delivers cmRNA (CST6) in unilateral diaphyseal femoral defects in rats

项目摘要骨再生是一个精心策划的动态过程，涉及几个关键因素，包括生长因子和细胞。骨组织工程旨在提供促进和增强自然骨再生的环境过程CST6是一种半胱氨酸蛋白酶抑制剂，其在多种细胞中高度表达。与具有任何溶骨性病变的骨髓瘤患者样本相比，缺乏任何溶骨性病变的骨髓瘤患者样本至少一处溶骨病变。体外初步研究表明，CST6（在重组体中）蛋白质形式）促进成骨细胞分化并抑制破骨细胞分化。 CmRNA具有完全在细胞质中发挥作用的独特优势（避免了细胞质中的细胞分裂）。需要进入核），从而导致所需的靶向瞬时表达。蛋白质具有巨大的潜力，可以克服蛋白质和基于DNA的方法具体而言，本研究旨在开发一种基于生物材料的释放cmRNA（CST6）以诱导体内骨再生的递送系统。我们目的是1）证明纳米颗粒负载的cmRNA（CST6）可以有效地触发成骨分化并抑制破骨细胞成熟，以及2）评估骨胶原支架的再生效率，提供cmRNA（CST6）在单侧大鼠股骨干缺损