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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 疾病的重要性，并领导联邦研究计划，为患有严重 TMD 的患者开发临床上更好的治疗方案。在严重的损伤或内部紊乱（ID）情况下，椎间盘需要通过手术切除，不幸的是，目前的异质椎间盘替代物（例如 Proplast-Teflon 和硅橡胶植入物）容易碎裂和撕裂，导致骨吸收和骨关节炎等并发症。针对这些缺点，人们评估了多种恢复颞下颌关节功能和运动能力的替代方法。应用组织工程原理用再生的“活”组织替代受损或患病的组织已显示出巨大的前景。通过这种方法，不会对关节周围的解剖结构造成额外的损害，并且新植入的重新设计的椎间盘将理想地适应关节的典型负载并恢复生理功能。在本提案中，我们利用天然猪 TMJ 盘作为异种体外支架，并进一步修改椎间盘结构以增强重新接种和运输条件，从而改善机械和生物功能。我们的初步数据显示了该方法的实用性，使脱细胞支架保持相似的机械性能到本机光盘。我们的目标是使用高精度激光烧蚀技术进一步开发一种生理相容的异种脱细胞颞下颌关节盘支架，其具有改良的微孔性，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再生椎间盘（人类细胞）作为患有严重 TMD 或 ID 的患者的完全椎间盘置换策略。为了实现这一目标，我们提出以下具体目标：具体目标。具体目标 1：表征天然衍生的颞下颌椎间盘支架，该支架保持天然细胞外基质特征并具有允许精确激光相互作用的参数。具体目标 2：设计一种高精度激光烧蚀范例，优化人工孔隙几何形状以提高传输能力，同时最大限度地减少由于体积损失和微环境破坏而导致的机械退化。然后评估细胞向内生长、细胞代谢和基因表达的接种方法和培养条件，以评估与支架结构变化相关的纤维软骨细胞功能。具体目标 3：测试以下假设：生理机械刺激鼓励纤维软骨细胞将 pTMJ 支架重塑为其天然机械特性，并且工程椎间盘可用于模拟疾病状况以进行进一步评估。我们假设，通过使用高精度激光烧蚀技术改善运输条件并增强细胞播种和营养输送，将实现机械和生物功能的显着改善。这些进步可能会为颞下颌关节（TMJ）椎间盘受损的患者提供更好的治疗选择。