Toward tissue engineering of facet cartilage

面向小面软骨的组织工程

基本信息

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
项目类别：
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

项目摘要

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.

项目概要该提案旨在设计同种异体关节突（小关节）关节表面重修（AZAR）系统通过遵循合理的实验方法来实现三个具体目标：AZAR 系统将由软骨组成组件（软骨部分）与骨样支架组件（骨部分）牢固地集成；这替换物将被固定在小关节的接受者骨床中。在目标 1 中，人类的三个层次小型猪的两性小面关节将得到全面表征，以确定 AZAR 系统的设计标准。 AZAR 系统将在目标 2 中分三个阶段进行设计和制造。首先，细胞松弛素-D 和透明质酸酶将应用于小型猪传代软骨细胞，以改造植入物的软骨部分具有模仿天然组织值的压缩特性。在同一阶段，使用赖氨酰氧化酶的方法像蛋白质 2 (LOXL2) 和拉伸刺激 (CoTenS) 将被鉴定以改善软骨部分达到天然组织水平。在目标 2，阶段 II 中，骨部分（即骨工程软骨正下方的部分）将进行微调，以实现最佳的软骨整合。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关节置换物，类似于目前用于人类患者的方法。最后，AZAR系统将被植入在未来的研究中转向双足模型之前，先用雄性和雌性小型猪检查其功效。该提案的成功完成将首次实现对整个关节表面进行表面重修。使用组织工程结构的关节关节。它还将揭示尚未探索的结构—— 研究很少的小关节中的功能关系。最后但并非最不重要的一点是，它将有助于新疗法的发展用于与关节面相关的疾病。