Toward tissue engineering of facet cartilage

面向小面软骨的组织工程

• 批准号: 10571696
• 负责人: Kyriacos A Athanasiou
• 金额: $ 33.89万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10571696
• 关键词: 3-Dimensional; 3D Print; Ablation; Acceleration; Address; Adult; Affect; Age; Allogenic; American; Animal Model; Animals; Architecture; Articulation; Beds; Biochemical; Biological; Biomechanics; Biomimetics; Cartilage; Cell Survival; Cells; Chondrocytes; Collaborations; Cytochalasin D; Data; Defect; Development; Diagnosis; Direct Costs; Disease; Doctor of Philosophy; Elderly; Engineering; Europe; Exhibits; Facet joint structure; Failure; Female; Foundations; Friction; Future; Hip Prosthesis; Human; Hyaluronidase; Immobilization; Implant; In Situ; Inferior; Joint Prosthesis; Joints; Knee; Knee Prosthesis; Libraries; Medial; Methods; Miniature Swine; Modeling; Modulus; Morbidity - disease rate; Morphology; Motion; Nerve Block; Nude Mice; Operative Surgical Procedures; Pain; Pathology; Patients; Phase; Phenotype; Play; Process; Property; Prosthesis; Prosthesis Implantation; Protein-Lysine 6-Oxidase; Proteins; Replacement Arthroplasty; Role; Secure; Shapes; Societies; Spine surgery; Stimulus; Structure-Activity Relationship; Surface; Surgeon; System; Temporomandibular Joint; Therapeutic Intervention; Time; Tissue Engineering; Tissues; Vertebral column; Weight-Bearing state; Work; articular cartilage; bone; cartilage implant; cartilage regeneration; cartilaginous; chronic pain; cost estimate; design; efficacy evaluation; experience; human female; improved; in vivo; joint destruction; male; mechanical properties; mimetics; minimally invasive; novel; novel therapeutics; osteochondral tissue; policy recommendation; preservation; reconstruction; rib bone structure; scaffold; self assembly; sex; success; working group

Project Summary This proposal seeks to engineer an allogeneic zygapophyseal (facet joint) articular resurfacing (AZAR) system by following a rational experimental approach in three specific aims: the AZAR system will consist of a cartilage component (chondro-portion) robustly integrated with a bone-like scaffold component (osteo-portion); the replacement will be secured in situ in the recipient bone bed of the facet joint. In Aim 1, three levels of human and minipig facet joints from both sexes will be fully characterized to define design criteria for the AZAR system. The AZAR system will be designed and fabricated through three phases in Aim 2. First, cytochalasin-D and hyaluronidase will be applied to minipig passaged chondrocytes to engineer the chondro-portion of the implant with compressive properties mimetic to native tissue values. In the same phase, methods for using lysyl oxidase like protein-2 (LOXL2) and tensile stimulation (CoTenS) will be identified to improve the tensile properties of the chondro-portion to native tissue levels. In Aim 2, Phase II, the pore size of the osteo-portion (i.e., the bone portion) directly beneath the engineered cartilage will be fine-tuned for optimum cartilage integration. In Aim 3, minimally invasive surgical methods will be developed for implanting a total facet replacement in the minipig, analogous to the ones currently employed in human patients. Finally, the AZAR system will be implanted into both male and female minipigs to examine its efficacy prior to moving to bipedal models in future studies. Successful completion of this proposal will allow, for the first time, resurfacing of an entire articular surface in a diarthrodial joint using a tissue engineered construct. It will also shed light on as-of-yet unexplored structure- function relationships in the poorly studied facet joint. Last, but not least, it will contribute toward new therapies for facet-related ailments.

项目摘要 该提案旨在设计一种同种异体关节突（小关节）关节表面置换（AZAR）系统 通过以下三个具体目标的合理实验方法：AZAR系统将由软骨组成， - 与骨样支架组件（骨部分）牢固整合的骨样支架组件（软骨部分）; 置换物将在小关节的受体骨床中原位固定。在目标1中，三个层次的人 将对两种性别的小型猪的关节突关节进行充分表征，以确定AZAR系统的设计标准。 AZAR系统将在Aim 2中通过三个阶段进行设计和制造。首先，细胞松弛素-D和 将透明质酸酶应用于小型猪传代的软骨细胞以工程化植入物的软骨部分 具有与天然组织值相似的压缩性能。在同一阶段，使用赖氨酰氧化酶的方法 如蛋白质-2（LOXL 2）和拉伸刺激（CoTenS）将被鉴定以改善 软骨部分到天然组织水平。在目标2阶段II中，骨部分的孔径（即，骨 部分）将被微调以获得最佳的软骨整合。在目标3中， 将开发微创手术方法用于在小型猪中植入全小面置换物， 类似于目前用于人类患者的方法。最后，AZAR系统将被植入到 雄性和雌性小型猪，以在未来的研究中转移到双足模型之前检查其功效。 成功完成该提案将首次允许在一个特定的时间内对整个关节面进行表面置换。 使用组织工程构建的关节。它还将揭示尚未探索的结构- 小关节的功能关系研究较少。最后，但并非最不重要的是，它将有助于开发新的治疗方法。 治疗面部疾病