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TMJ疾病的重要性，并领导联邦研究计划，为患有严重TMD患者的人开发临床上卓越的治疗方案。在 严重的损伤或内部危险（ID）的椎间盘被手术去除，不幸的是，当前的同种异体椎间盘替换（例如预防性TEFLON和SILASTIC植入物）易于碎裂和撕裂，导致骨吸收和骨关节炎等并发症。为了应对这些缺点，已经评估了各种用于恢复TMJ功能和运动能力的替代方法。使用组织工程原理的应用来替代被再生的“活”组织替代受损或患病的组织的诺言。使用这种方法，将不会造成关节的周围解剖结构的额外损害，并且新植入的重新设计的椎间盘理想地可以容纳关节的典型负载并恢复生理功能。在此提案中，我们利用天然猪TMJ碟作为异种 离体支架，并进一步修改了圆盘结构，以增强恢复和运输条件，以改善机械和生物学功能。我们的初步数据显示了该方法的实用性，其脱细胞支架保持机械性能相似 到本地光盘。我们的目标是使用高精度激光消融技术进一步开发一种具有修改的微孔度的生理兼容的颞叶颞叶椎间盘椎间盘支架，以克服运输和细胞迁移缺陷。我们的长期目标是将此脚手架用作直接的细胞植入物或再生盘（人类细胞）作为患有严重TMD或ID的人的总圆盘替代策略。为了实现这一目标，我们提出以下特定目标：特定目的。特定目的1：表征自然衍生的颞下椎间盘支架，该椎间盘支架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。具体目标2：设计高精度激光消融范式，可优化人工孔隙率几何形状，以便传输能力，同时由于体积损失和微环境中断而导致的机械降解。然后评估播种方法和培养条件，以评估细胞向内生长，细胞代谢和基因表达，以评估与脚手架结构变化有关的纤维软骨细胞功能。特定目的3：检验以下假设：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性能，并且该工程椎间盘可用于模拟疾病条件以进行进一步评估。我们假设，通过使用高精度激光消融技术改善运输条件并改善细胞播种和养分递送，可以实现机械和生物学功能的显着改善。这些进步可能会导致患有不可避免受损的颞下颌关节（TMJ）椎间盘的患者改善治疗选择。 公共卫生相关性：食品药品监督管理局估计，美国有25％的人口遭受了颞下颌疾病（TMD），其中约70％的人遭受了TMJ的疾病，损害或畸形折磨光盘。在严重损坏或内部危险（ID）的情况下，椎间盘被手术切除，不幸的是，目前的治疗远远不够。为了应对这些缺点，我们将使用高精度的激光消融技术来开发一种具有修改的微孔力的生理兼容的临时颞叶颞关节盘脚手架，以克服运输和细胞迁移缺陷有效地增强组织的整体磁盘再生策略严重的TMD或ID。