A crosslinked cartilage-derived matrix for cartilage tissue engineering

用于软骨组织工程的交联软骨衍生基质

• 批准号: 8312139
• 负责人: Bradley T Estes
• 金额: $ 29.93万
• 依托单位: CYTEX THERAPEUTICS INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-17 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8312139
• 关键词: Address; Adipose tissue; Adult; Affect; American; Anatomy; Arthralgia; Arthritis; Autologous Transplantation; Biochemical; Biocompatible Materials; Biological; Biomechanics; Cartilage; Cartilage Matrix; Cell Culture Techniques; Cells; Chemicals; Chondrogenesis; Clinical; Communities; Core Facility; Defect; Degenerative polyarthritis; Development; Differentiation and Growth; Disease; Ear; Elastic Cartilage; Engineering; Extracellular Matrix; Functional disorder; Future; Gene Expression; Goals; Growth; Harvest; Head and neck structure; Histologic; Human; Implant; In Situ; In Vitro; Infiltration; Inflammation; Injury; Joint repair; Joints; Maintenance; Measures; Mechanics; Medical; Mesenchymal Stem Cells; Methods; Modeling; Molds; Molecular; Molecular Profiling; Monitor; Morbidity - disease rate; Morphology; Natural regeneration; Nose; Nucleic Acids; Operative Surgical Procedures; Orthopedics; Oryctolagus cuniculus; Pathology; Patients; Performance; Phase; Phenotype; Plastic Surgical Procedures; Plastics; Procedures; Process; Property; Protein Analysis; Proteins; Proteome; Proteomics; Quality Control; Reaction; Reconstructive Surgical Procedures; Risk; Risk Factors; Safety; Sampling; Shapes; Small Business Innovation Research Grant; Spatial Distribution; Stem cells; Synovial Membrane; Technology; Testing; Time; Tissue Engineering; Tissues; Toxic effect; Trachea; Trauma; Treatment Cost; Ultraviolet Rays; Weight-Bearing state; Work; articular cartilage; base; bone; cartilage allograft; cartilage development; cartilage repair; crosslink; disability; economic impact; immunogenic; implantation; improved; in vivo; insight; joint injury; long bone; macrophage; meetings; novel; physical process; protein expression; reconstruction; repaired; scaffold; success; tissue repair

DESCRIPTION (provided by applicant): The treatment of injuries or diseases affecting articular or elastic cartilage poses important unmet challenges to the medical community. The goal of this Phase I SBIR is to further the development of a method for the manufacture of a biologically-derived biomaterial that can maintain a pre-defined anatomical shape, while supporting the synthesis of a new tissue of a cartilage phenotype for the purpose of joint reconstruction or for reconstructive or plastic surgery. The novelty in this work entails the use o a biologically-derived material we have developed based solely on physical processing of allograft cartilage tissue. Our previous studies have demonstrated that this porous cartilage-derived matrix (CDM) can support, and even promote, chondrogenesis of both adipose-derived stem cells (ASCs) and mesenchymal stem cells (MSCs), resulting in a tissue that is biochemically and biomechanically similar to cartilage. To improve the shape retention properties of the biologically-derived biomaterial, CDM scaffolds will be cross-linked using chemical, UV light, or dehydrothermal processing. Following cross-linking of the matrix, the focus will be directed toward analysis of the proteome of the cross-linked CDM biomaterials to assess protein expression profiles between the different cross-linking treatments and also provide a baseline for future quality control during manufacture. The in vitro efficacy of the various cross-linked scaffolds seeded with ASCs or MSCs with respect to chondrogenic induction, shape maintenance, and mechanical integrity maintenance will also be evaluated. Measures of gene expression, tissue accumulation, and functional properties will be made using molecular, histologic, and biomechanical testing methods. Finally, a rabbit in vivo cartilage repair defect model will be used to assess the in vivo performance of the CDM by evaluating the regenerated tissue and overall joint tissue histologically and mechanically in comparison to the biochemical and biomechanical properties of native articular cartilage. Additionally, the overall toxicity and host immunological reaction to the CDM will be evaluated in this cartilage defect model. This scaffold technology will hopefully provide a novel means of developing tissue engineered constructs that are biomechanically functional at the time of creation and more easily integrated into host tissues in the body following surgical implantation. An improved level of biomechanical function will hopefully increase the level of success in the engineered repair of articular as well as elastic cartilage for applications in orthopaedic or plastic/reconstructive surgery. PUBLIC HEALTH RELEVANCE: The goal of this Phase I SBIR project is to develop a novel tissue engineered scaffold consisting of processed articular cartilage extracellular matrix that has been cross-linked so it can maintain a pre-defined anatomical shape. The ability of this porous, biologically active scaffold to support cartilaginous tissue formation will be tested using human adipose-derived or mesenchymal stem cells in long-term in vitro culture. Additionally, cartilaginous tissue growth and the host immunological reaction to the biomaterial will be monitored in an in vivo rabbit cartilage repair defect model. The ultimate goal of this project is o develop engineered tissues for treating cartilage defects in orthopaedic and/or reconstructive surgery applications.

描述(由申请人提供)：影响关节软骨或弹性软骨的损伤或疾病的治疗对医学界构成了重要的未满足的挑战。第一阶段SBIR的目标是进一步开发一种生物衍生生物材料的制造方法，该材料可以保持预先定义的解剖形状，同时支持合成用于关节重建或重建或整形手术的软骨表型的新组织。这项工作的新颖性需要使用我们开发的一种生物衍生材料，这种材料完全基于对同种异体软骨组织的物理处理。我们以前的研究已经证明，这种多孔的软骨衍生基质(CDM)可以支持甚至促进脂肪干细胞(ASCs)和间充质干细胞(MSCs)的软骨形成，从而形成一种在生物化学和生物力学上与软骨相似的组织。为了改善生物衍生生物材料的形状保持性能，CDM支架将使用化学、紫外光或去水热处理进行交联。在对基质进行交联化之后，重点将放在分析交联型清洁发展机制生物材料的蛋白质组上，以评估不同交联型处理之间的蛋白质表达谱，并为今后制造过程中的质量控制提供基线。此外，还将评估种植有ASCs或MSCs的各种交联型支架在软骨诱导、形状保持和机械完整性方面的体外效果。基因表达、组织积累和功能特性的测量将使用分子、组织学和生物力学测试方法进行。最后，我们将利用兔在体软骨修复缺陷模型，通过评估再生组织和整个关节组织的组织学和力学性能，并与天然关节软骨的生化和生物力学特性进行比较，来评估CDM的体内性能。此外，将在该软骨缺损模型中评估整体毒性和宿主对CDM的免疫反应。这种支架技术有望提供一种开发组织工程化结构的新方法，这些结构在创建时具有生物力学功能，并在手术植入后更容易整合到体内的宿主组织中。生物力学功能水平的提高有望提高关节软骨和弹性软骨工程修复的成功率，应用于矫形外科或整形/重建外科。 公共卫生相关性：这个第一阶段SBIR项目的目标是开发一种新型的组织工程支架，该支架由经过处理的关节软骨细胞外基质组成，这种基质已经被交联，从而能够保持预先定义的解剖形状。这种多孔的生物活性支架支持软骨组织形成的能力将使用 人脂肪来源干细胞或间充质干细胞长期体外培养。此外，将在活体兔软骨修复缺陷模型中监测软骨组织生长和宿主对生物材料的免疫反应。该项目的最终目标是开发用于治疗骨科和/或重建外科应用中的软骨缺陷的工程化组织。