Cartilage storage solution for chondrocyte viability and biomaterial preservation

用于软骨细胞活力和生物材料保存的软骨储存解决方案

• 批准号: 8447752
• 负责人: Kelvin G.M. Brockbank
• 金额: $ 31.26万
• 依托单位: CELL AND TISSUE SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-27 至 2014-08-26
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8447752
• 关键词: Allogenic; Allografting; Animal Model; Animals; Biocompatible Materials; Biological Preservation; Cartilage; Cartilage Matrix; Castor; Cell Survival; Cells; Chemistry; Chondrocytes; Clinical; Clinical Research; Collagen Type I; Collagen Type II; Cryopreservation; Culture Media; Defect; Degenerative polyarthritis; Deterioration; Doxycycline; Drug Formulations; Eagles; Ensure; Environment; Enzyme Inhibitor Drugs; Enzyme Inhibitors; Enzymes; Extracellular Matrix; Family suidae; Future; Gene Expression; Genes; Human; In Vitro; Institutes; Investigation; Life; Maintenance; Marketing; Matrix Metalloproteinase Inhibitor; Matrix Metalloproteinases; Metalloproteases; Methods; Nutrient; Organ Preservation Solutions; Outcome; Patients; Permeability; Pharmacopoeias; Phase; Phenotype; Plasma; Procedures; Property; Proteins; Publishing; Recovery; Research; Review Literature; Small Business Innovation Research Grant; Solutions; Supplementation; Surface; Surveys; System; Technology; Testing; Time; Tissue Engineering; Tissues; Translations; Transplantation; Trauma; United States; Universities; Work; aggrecan; articular cartilage; base; cartilage cell; cartilage repair; clinically significant; commercialization; design; experience; extracellular; implantation; in vivo; osteochondral tissue; public health relevance; reconstruction; repaired; tissue culture; tissue/organ preservation

DESCRIPTION (provided by applicant): Resurfacing of articular cartilage with cold stored osteochondral allografts is employed clinically for repair of trauma and osteoarthritis-induced articular cartilage surface damage. Chondrocyte viability of transplanted articular cartilage is accepted as one of the determinants of outcome following osteochondral allograft transplantation. Refrigerated storage methods used for cartilage storage prior to clinical cartilage utilization need to be carefully evaluated because the tissue may be experiencing clinically significant deterioration during storage. We have recently investigated cartilage cell viability and matrix permeability during storage in culture medium, as well as storage solutions, and found that both deteriorate within the time frames that they are utilized for clinical procedures. Culture medium that preserves chondrocyte viability best under cold refrigerated storage conditions does not preserve matrix permeability and, vice versa, nutritionally deficient solutions that preserve matrix permeability have significantly less cell viability. This objective ill be developed in three specific aims. In these aims two solution formulations, one based on intracellular and the other on extracellular milieu designs will be investigated. Chondrocyte viability, chemistry, biomaterial properties and gene expression will be compared over time during porcine cartilage storage. The gene expression studies will determine which formulation maintains normal untreated cartilage expression of Sox9, aggrecan, collagen type II (versus dedifferentiation marker collagen type I), cartilage oligomeric matrix, a matrix resorption marker plus protein and hypertrophic marker genes. The solution that provides the longest preservation of chondrocytes with a normal untreated chondrocyte phenotype with minimal if any cartilage biomaterial changes will be selected for further investigation in vivo and translation to human cartilage in a subsequent Phase II SBIR application.

描述（由申请人提供）：用冷储存的骨软骨同种异体移植关节软骨在临床上用于修复创伤和骨关节炎诱导的关节软骨表面损伤。移植关节软骨的软骨细胞生存力被接受为骨软骨同种异体移植后结果的决定因素之一。需要仔细评估用于临床软骨之前的软骨存储的冷藏储存方法，因为该组织在存储过程中可能正在经历临床意义的恶化。我们最近研究了在培养基中存储期间的软骨细胞活力和基质渗透性以及储存溶液，并发现两者在时间范围内都在用于临床程序的时间范围内恶化。在冷冷藏储存条件下保留软骨细胞生存力的培养基不能保留基质渗透性，反之亦然，保留基质渗透率的营养缺陷溶液具有明显较小的细胞生存能力。这一目标将以三个具体目标发展。在这些目标中，将研究一种基于细胞内的溶液制剂，另一个基于细胞外环境设计。在猪软骨存储期间，将比较软骨细胞的生存力，化学，生物材料特性和基因表达。基因表达研究将确定哪种配方保持了SOX9，Aggrecan，II型胶原蛋白（与去分化标记I型胶原蛋白I型）的正常未经处理的软骨表达，软骨寡聚型基质，基质吸收标记标记物加蛋白质和肥大标记基因。如果将选择任何软骨生物材料变化，则提供最小的未经处理的软骨细胞表型的软骨细胞保存最长的解决方案，以便在随后的II阶段II SBIR应用中选择任何软骨生物材料变化，并在体内进行进一步研究。