Novel Computational Biomechanics Approach to Design of Bioengineered Tissue Construct for Meniscus Defect Repair

用于半月板缺损修复的生物工程组织结构设计的新型计算生物力学方法

• 批准号: 10172849
• 负责人: Alicia R Jackson
• 金额: $ 31.38万
• 依托单位: UNIVERSITY OF MIAMI CORAL GABLES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-20 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10172849
• 关键词: Acute; Address; Adopted; Anisotropy; Atomic Force Microscopy; Behavior; Biochemical; Biomechanics; Biomedical Engineering; Cartilage; Cells; Collagen; Communities; Computer Assisted; Computer Models; Custom; Data; Data Set; Defect; Degenerative polyarthritis; Development; Diffusion; Environment; Excision; Failure; Fibrocartilages; Glycosaminoglycans; Goals; Homeostasis; Human; Incidence; Joints; Knee; Knee Injuries; Knowledge; Libraries; Lubrication; Measures; Meniscus structure of joint; Methods; Modeling; Natural regeneration; Operative Surgical Procedures; Outcome; Partition Coefficient; Performance; Permeability; Play; Process; Property; Replacement Arthroplasty; Research; Role; Seeds; Signal Transduction; Structure; Techniques; Testing; Theoretical model; Tissue Engineering; Tissues; Translating; Water; base; behavioral construct; biomechanical model; cell behavior; clinical translation; computerized tools; data archive; design; electrical property; fluorescence imaging; human tissue; improved; innovation; meniscal tear; novel; organizational structure; preservation; repaired; scaffold; solute; tool; young adult

PROJECT SUMMARY The meniscus fibrocartilage in the knee plays an essential role in load distribution, congruency, and joint stability, and is therefore necessary for proper joint biomechanics. Meniscus tears are the most frequent type of knee injury in active younger adults. Successful repair of tears decreases the development of osteoarthritis and subsequent need for joint replacement. Synthetic scaffolds have been developed to address segmental tissue defects; however, midterm outcomes have shown high failure rates and progression of chondral wear. The ultimate goal of this research is to develop a novel, long-lasting treatment for meniscus tears that shifts the treatment paradigm from one of removal of tissue to one of regeneration and preservation of function. In this application, our objective is to adopt a computationally assisted bioengineering approach to repair meniscal defects. We hypothesize that a scaffold closely mimicking structure, composition, biomechanics, transport, and electrokinetics of the healthy native tissue will integrate into the meniscus and will regenerate meniscal tissue at the defect. While some biomechanical properties of the meniscus have been investigated, little is known about meniscal transport and elektrokinetic properties, which are key determinants of cellular behavior and related tissue homeostasis. Using our expertise in electromechanics, transport and computational modeling of cartilaginous tissues, we will develop a novel library of design criteria, based on human meniscus properties (Aim 1). This will allow us to provide new structure-function relations for tissue properties in relation to biochemical composition and structural organization of the tissue. Based on this new knowledge, we will develop a new computational tool to evaluate the mechano-electrochemical environment (MEC) in meniscus tissues (Aim 2). Then, we will simulate the presence of meniscal defects repaired with tissue engineered scaffolds. We will investigate the effect of structural and compositional properties of the scaffold on MEC signals in order to identify optimal ranges of such parameters to recapitulate electromechanics and functional behavior of the native meniscal tissue. This will allow us to formulate initial design criteria for our novel scaffold, which will be further refined via an iterative process; at each iteration, (1) MEC properties of the scaffold will be measured and compared to those of the native tissue and, if necessary, (2) the design parameters of the scaffold will be tuned/improved as per indications of the computational model (Aim 3). Finally, we will seed meniscus fibrochondrocytes in the scaffold and integrate it into a meniscus defect using an ex vivo defect model. The scaffold’s biomechanical properties, cellular activity/viability post-culture and integration into a meniscus defect will be assessed and compared to those of a commercially available synthetic scaffold for meniscus repair. We present an innovative approach for bioengineering scaffolds for meniscus repair. Our rationally designed scaffold will provide an ideal environment for meniscus cells, which will translate to successful integration and regeneration of meniscus tissue at the defect, giving this project high potential for clinical translation.

项目摘要 膝关节半月板纤维软骨在载荷分布、一致性和关节稳定性方面起着重要作用， 因此对于适当的关节生物力学是必需的。半月板撕裂是膝关节最常见的类型 在年轻人的积极伤害。撕裂的成功修复减少了骨关节炎的发展， 随后需要进行关节置换。合成支架已经被开发用于解决节段性组织 缺陷;然而，中期结果显示失败率高，且软骨磨损进展。 这项研究的最终目标是开发一种新的，持久的治疗半月板撕裂的转移 从切除组织到再生和保留功能的治疗模式。在这 应用，我们的目标是采用计算辅助生物工程的方法来修复视网膜 缺陷我们假设，一个紧密模仿结构，组成，生物力学，运输， 健康的天然组织的电动力学将整合到半月板中 缺陷。虽然已经研究了半月板的一些生物力学特性，但对半月板的生物力学特性知之甚少。 细胞转运和电动力学特性，它们是细胞行为和相关 组织内稳态利用我们在机电、运输和计算建模方面的专业知识， 软骨组织，我们将开发一个新的设计标准库，基于人类半月板的属性 (Aim 1）。这将使我们能够为组织特性提供新的结构-功能关系， 组织的生化组成和结构组织。基于这些新知识，我们将开发 一种新的计算工具来评估半月板组织中的机械电化学环境（MEC）（Aim 2）的情况。然后，我们将模拟存在的组织工程支架修复牙周缺损。我们将 研究支架的结构和组成特性对MEC信号的影响，以鉴定 这些参数的最佳范围，以概括本机的机电和功能行为， 直肠组织。这将使我们能够为我们的新型支架制定初始设计标准，这将进一步 通过迭代过程进行细化;在每次迭代中，（1）将测量支架的MEC性质， 如果需要，（2）支架的设计参数将 根据计算模型的指示进行调整/改进（目标3）。最后，我们将种植半月板 将纤维软骨细胞植入支架中，并使用离体缺损模型将其整合到半月板缺损中。的 支架的生物力学特性、培养后的细胞活性/存活力以及与半月板缺损的整合 将评估并与用于半月板修复的市售合成支架进行比较。 我们提出了一种创新的方法，半月板修复的生物工程支架。我们合理设计的 支架将为半月板细胞提供理想的环境，这将转化为成功的整合， 半月板组织在缺损处的再生，使该项目具有很高的临床转化潜力。

项目成果

EFFECTS OF SOLUTE SIZE AND TISSUE COMPOSITION ON MOLECULAR AND MACROMOLECULAR DIFFUSIVITY IN HUMAN KNEE CARTILAGE.

• DOI: 10.1016/j.ocarto.2020.100087
• 发表时间: 2020-12-01
• 期刊: Osteoarthritis and cartilage open
• 作者: Travascio, Francesco;Valladares-Prieto, Sabrina;Jackson, Alicia R
• 通讯作者: Jackson, Alicia R

Mechanical properties of meniscal circumferential fibers using an inverse finite element analysis approach.

• DOI: 10.1016/j.jmbbm.2022.105073
• 发表时间: 2022-03
• 期刊: JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
• 影响因子: 3.9
• 作者: De Rosa, Massimiliano;Filippone, Giovanni;Best, Thomas M.;Jackson, Alicia R.;Travascio, Francesco
• 通讯作者: Travascio, Francesco

Heterogeneity of dynamic shear properties of the meniscus: A comparison between tissue core and surface layers.

半月板动态剪切特性的异质性：组织核心层和表层之间的比较。

• DOI: 10.1002/jor.25495
• 发表时间: 2023
• 期刊: Journal of orthopaedic research : official publication of the Orthopaedic Research Society
• 作者: Schwartz,Gabi;Morejon,Andy;Gracia,Julissa;Best,ThomasM;Jackson,AliciaR;Travascio,Francesco
• 通讯作者: Travascio,Francesco

Compressive Properties and Hydraulic Permeability of Human Meniscus: Relationships With Tissue Structure and Composition.

• DOI: 10.3389/fbioe.2020.622552
• 发表时间: 2020
• 期刊: Frontiers in bioengineering and biotechnology
• 影响因子: 5.7
• 作者: Morejon A;Norberg CD;De Rosa M;Best TM;Jackson AR;Travascio F
• 通讯作者: Travascio F

Viscoelastic and equilibrium shear properties of human meniscus: Relationships with tissue structure and composition.

• DOI: 10.1016/j.jbiomech.2021.110343
• 发表时间: 2021-05-07
• 期刊: Journal of biomechanics
• 影响因子: 2.4
• 作者: Norberg C;Filippone G;Andreopoulos F;Best TM;Baraga M;Jackson AR;Travascio F
• 通讯作者: Travascio F