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 该提案旨在设计同种异体zygapophyseal（facet intoct）关节重铺（Azar）系统 通过在三个特定目标中遵循合理的实验方法：Azar系统将由软骨组成 与骨状的支架成分（骨段）鲁棒整合的成分（软骨段）；这 替换将在刻面关节的受体骨床原位固定。在AIM 1中，三个级别的人类 两性的Minipig Facet关节将被充分表征，以定义Azar系统的设计标准。 Azar系统将在AIM 2中的三个阶段进行设计和制造。首先，Cytochalasin-D和 透明质酸酶将应用于Minipig传递的软骨细胞，以设计植入物的软骨段 具有模拟天然组织值的压缩特性。在同一阶段，使用赖氨酸氧化酶的方法 将确定蛋白质2（LOXL2）和拉伸刺激（Cotens），以提高拉伸特性 向天然组织水平的软骨段。在AIM 2中，第二阶段，骨的孔径（即骨头） 一部分）直接在工程软骨下方进行微调，以进行最佳软骨整合。在AIM 3中， 将开发最小的侵入性手术方法，以植入Minipig中的总面部替代品， 类似于目前在人类患者中使用的人。最后，Azar系统将被植入 在未来的研究中，男性和女性迷你典礼都在转向两足动物模型之前检查其功效。 该提案的成功完成将首次允许在整个关节表面重新铺面 使用组织工程构建体的腹膜关节。它还将阐明尚未探索的结构 - 研究较少的小方接头中的功能关系。最后但并非最不重要的一点是，它将有助于新疗法 与方面有关的疾病。