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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，为严重TMD患者开发临床优越的治疗方案。在