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Development of an ex vivo derived laser drilled temporomandibular disc scaffold

离体激光钻孔颞下颌椎间盘支架的开发

基本信息

批准号：
8505476
负责人：
Peter Stuart McFetridge
金额：
$ 16.98万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-05 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8505476
关键词：
Ablation Americas Anatomy Biochemical Biological Process Biomechanics Bone Resorption Carbon Dioxide Cartilage Cell Survival Cell physiology Cell surface Cell-Cell Adhesion Cells Characteristics Clinical Collagen Computer software Culture Techniques Data Deformity Degenerative polyarthritis Dermis Development Disease Engineering Evaluation Extracellular Matrix Family suidae Fatty acid glycerol esters Foreign-Body Reaction Freeze Drying Frequencies Functional disorder Gene Expression Goals Health Human Implant Inherited Jaw Joints Lasers Lead Life Liquid substance Mechanical Stimulation Mechanics Metabolism Methodology Morphology Movement National Institute of Dental and Craniofacial Research Natural regeneration Nature Nutrient Operative Surgical Procedures Pathology Patients Pattern Penetration Phenotype Physiologic pulse Physiological Porosity Process Property Rehydrations Research Silastic Simulate Specific qualifier value Stress Structure Structure of articular disc of temporomandibular joint Techniques Teflon Temporomandibular Joint Temporomandibular Joint Disorders Testing Thick Tissue Engineering Tissue Grafts Tissues United States United States Food and Drug Administration Variant Water articular cartilage cell motility design driving force experience functional restoration improved joint loading response scaffold tissue regeneration

项目摘要

DESCRIPTION (provided by applicant): The National Institute of Dental and Craniofacial Research (NIDCR) recognizes the significance of TMJ disorders and leads the Federal research initiative to develop clinically superior treatment options for those suffering with severe TMD. In severe cases of damage or internal derangement (ID) the disc is surgically removed, unfortunately current alloplastic disc replacements such as Proplast-Teflon and Silastic implants are prone to fragmentation and tearing, leading to complications such as bone resorption and osteoarthritis. In response to these shortcomings, a variety of alternative approach's for restoring the function and movement capabilities of the TMJ have been assessed. A great deal of promise has been shown with the application of tissue engineering principles to replace damaged or diseased tissues with regenerated, 'living' tissues. With this methodology no additional damage to the surrounding anatomy of the joint would be experienced, and the newly implanted re-engineered disc would ideally accommodate typical loads of the joint and regain physiologically functionality. In this proposal we utilize a native porcine TMJ disc as a xenogenic ex vivo scaffold, and further modified the discs structure to enhance reseeding and transport conditions to improve both mechanical and biological function. Our preliminary data has shown the utility of the approach with decellularized scaffolds maintaining mechanical properties similar to native discs. Our goal is to further develop a physiologically compatible xenogenic acellular temporomandibular articular disc scaffold with modified microporosity using a high precision laser ablation technique to overcome transport and cell migration deficiencies. Our longer-term goal is to use this scaffold either as a direct acellular implant or as a regenerated disc (human cells) as a total disc replacement strategy for those suffering with severe TMD or ID. To accomplish this goal we propose the following specific aims: Specific aims. Specific Aim 1: Characterize a naturally derived temporomandibular disc scaffold which maintains native extracellular matrix characteristics and has parameters that allow for precise laser interactions. Specific Aim 2: Design a high precision laser ablation paradigm that optimizes artificial porosity geometry for transport capability while minimizing mechanical degradation due to volume loss and microenvironment disruption. Then to evaluate seeding methodology and culture conditions for cell ingrowth, cell metabolism, and gene expression to assess fibrochondocyte cell function in relation to structural changes to the scaffold. Specific Aim 3: Test the hypothesis that physiologic mechanical stimulation encourages fibrochondrocytes to remodel the pTMJ scaffold toward its native mechanical properties, and that the engineered disc can be used to simulate disease conditions for further evaluation. We hypothesize that by improving transport conditions and enhancing cell seeding and nutrient delivery using a high precision laser ablation technique that significant improvements in both mechanical and biological function will be attained. These advances may lead to improved treatment options for patients suffering with irreparably damaged Temporomandibular Joint (TMJ) discs.

描述(由申请人提供)：国家牙科和颅面研究所(NIDCR)认识到TMJ障碍的重要性，并领导联邦研究计划为患有严重TMD的患者开发临床上优越的治疗方案。在……里面严重的损伤或内部排列紊乱(ID)椎间盘被手术取出，不幸的是，目前的同种异体椎间盘置换，如Proplast-Teflon和硅橡胶植入物，容易发生碎裂和撕裂，导致骨吸收和骨关节炎等并发症。针对这些缺点，对恢复TMJ功能和运动能力的各种替代方法进行了评估。随着组织工程学原理的应用，用再生的“活”组织取代受损或患病的组织，已经显示出很大的希望。这种方法不会对关节周围的解剖造成额外的损害，新植入的重新设计的椎间盘将理想地适应关节的典型负荷并恢复生理功能。在这项建议中，我们使用本地猪的TMJ盘作为异种并进一步改进了圆盘结构，改善了补种和运输条件，改善了机械和生物功能。我们的初步数据表明，在力学性能保持相似的脱细胞支架上，该方法是有效的到本机光盘。我们的目标是利用高精度的激光消融技术，进一步开发一种具有改良微孔的生理兼容的异种脱细胞关节盘支架，以克服运输和细胞迁移的缺陷。我们的长期目标是使用这种支架作为直接无细胞植入物或作为再生的椎间盘(人类细胞)作为严重TMD或ID患者的全盘替换策略。为了实现这一目标，我们提出以下具体目标：具体目标1：描述一种自然衍生的、保持天然细胞外基质特性并具有允许精确激光相互作用的参数的颞下颌关节盘支架。具体目标2：设计一种高精度激光消融范例，在最大限度地减少因体积损失和微环境破坏而导致的机械退化的同时，优化人工孔道几何形状以提高传输能力。然后评估种植方法和培养条件对细胞生长、细胞代谢和基因表达的影响，以评估纤维软骨细胞功能与支架结构变化的关系。具体目标3：测试生理性机械刺激促使纤维软骨细胞按照其固有的机械性能重塑pTMJ支架的假设，以及工程化盘可用于模拟疾病条件进行进一步评估。我们假设，通过使用高精度激光消融技术改善运输条件、加强细胞种植和营养输送，将在机械和生物功能方面实现显着改善。这些进展可能会为患有不可修复的颞下颌关节(TMJ)损伤的患者带来更好的治疗选择。