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

• 批准号: 8386352
• 负责人: Peter Stuart McFetridge
• 金额: $ 19.77万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-05 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8386352
• 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

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. PUBLIC HEALTH RELEVANCE: It is estimated by the Food and Drug Administration that 25 percent of the United States of America populous suffer from a Temporomandibular Disorder (TMD) and about 70 percent of those people are afflicted by disease, damage, or deformity of the TMJ disc. In severe cases of damage or internal derangement (ID) the disc is surgically removed, unfortunately current treatments are far from sufficient. In response to these shortcomings we will 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 effectively enhancing tissue regeneration for use as a total disc replacement strategy for those suffering with severe TMD or ID.

描述（由申请人提供）：国家牙科和颅面研究所（NIDCR）认识到颞下颌关节疾病的重要性，并领导联邦研究计划，为严重TMD患者开发临床上级治疗方案。在 在损伤或内部紊乱（ID）的严重情况下，通过手术移除椎间盘，不幸的是，目前的异体椎间盘置换物，例如Proplast-Teflon和Silastic植入物，易于碎裂和撕裂，导致并发症，例如骨吸收和骨关节炎。针对这些缺点，已经评估了用于恢复TMJ的功能和运动能力的各种替代方法。应用组织工程原理，用再生的“活”组织代替受损或患病的组织，已经显示出很大的希望。采用这种方法，不会对关节周围的解剖结构造成额外的损伤，并且新植入的再造椎间盘将理想地适应关节的典型载荷并恢复生理功能。在这项建议中，我们利用一个本地猪颞下颌关节盘作为异种 离体支架，并进一步修饰盘结构以增强再播种和运输条件，从而改善机械和生物功能。我们的初步数据表明，该方法的实用性与脱细胞支架保持类似的机械性能 本地光盘我们的目标是进一步开发一种生理上相容的异种脱细胞颞下颌关节盘支架，采用高精度激光消融技术，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的脱细胞植入物或再生椎间盘（人类细胞）作为严重TMD或ID患者的全椎间盘置换策略。为了实现这一目标，我们提出了以下具体目标：具体目标。具体目标1：表征天然来源的颞下颌关节盘支架，其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。具体目标二：设计高精度激光烧蚀范例，优化人造孔隙几何形状以实现输送能力，同时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。然后评价接种方法和细胞向内生长、细胞代谢和基因表达的培养条件，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：测试生理机械刺激促使纤维软骨细胞朝向其天然机械特性重塑pTMJ支架的假设，以及工程化椎间盘可用于模拟疾病条件以进行进一步评估的假设。我们假设，通过改善运输条件和提高细胞接种和营养输送使用高精度激光烧蚀技术，在机械和生物功能的显着改善将实现。这些进展可能会为患有不可修复的颞下颌关节（TMJ）椎间盘损伤的患者提供更好的治疗选择。 公共卫生相关性：据美国食品和药物管理局估计，美国人口的25%患有颞下颌关节紊乱病（TMD），其中约70%的人患有TMJ盘的疾病、损伤或畸形。在严重的损伤或内部紊乱（ID）的情况下，通过手术切除椎间盘，不幸的是，目前的治疗远远不够。针对这些缺点，我们将开发一种生理上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，使用高精度激光消融技术来克服运输和细胞迁移缺陷，有效地增强组织再生，用作严重TMD或ID患者的全椎间盘置换策略。