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Multiscale models of fibrous interface mechanics

纤维界面力学的多尺度模型

基本信息

批准号：
10037326
负责人：
Guy M Genin
金额：
$ 54.54万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10037326
关键词：
Adhesions Adhesives Animal Model Automobile Driving Behavior Biological Models Bone Regeneration Bone Tissue Botulinum Toxin Type A Brain Characteristics Collagen Collagen Diseases Collagen Fiber Connective Tissue Disease Environment Failure Fiber Foundations Friction Hernia In Vitro Injury Intra-abdominal Knowledge Laparotomy Lead Length Ligaments Location Machine Learning Mechanics Meniscus structure of joint Mesentery Minerals Modeling Modification Mus Musculoskeletal Nature Nervous system structure Operative Surgical Procedures Pain Paralysed Pathologic Pathology Patients Peritoneal Physiological Pia Mater Process Rotator Cuff Running Skin Slide Source Specimen Stress Structure Surface System Technology Tendinopathy Tendon structure Testing Tissue Sample Tissues Work absorption bone cranium crosslink design disability experimental study improved in vivo mathematical model mechanical behavior millimeter molecular dynamics multi-scale modeling nano nanocrystal nanoscale older patient repaired treadmill

项目摘要

PROJECT SUMMARY Interfaces between tissues either transfer load (requiring toughness) or provide a smooth surface (requiring low friction). Fibrous interfaces are very effective at transferring load between tissues, e.g., at connective tissue-bone interfaces (“entheses”), peritoneal-mesentery interfaces, interfaces between layers of the vasculature, and the pia mater. These interfaces require toughness to resist high stresses associated with material mismatches. Surgical repair can lead to smooth interfaces becoming fibrous, (e.g., following hernia surgery) or to tough interfaces becoming weak (e.g., following tendon- and ligament-to-bone repair). In older patients with large rotator cuff repairs, for example, where the desired attachment is not reformed, up to 94% of surgical repairs fail. These challenges arise in part because the features that endow fibrous interfaces with toughness are not known. We therefore propose to develop a comprehensive modeling and experimental approach for studying the factors underlying the transition from tough to weak in a fibrous interface. Our previous work motivates the hypothesis that disorder is a key toughening feature of fibrous attachments. We will focus initially on the example of tendon attaching to bone, in which microscale disorder underlies the ordered macroscale, graded transition between the two tissues, as a foundation for studying the general problem of adhesion throughout the body. We predict that disorder enhances energy absorption by distributing failure processes and energy absorption over larger volumes of tissue. We propose this as a fundamental mechanism by which fibrous interfaces in the body transfer load effectively. We will test these ideas through two aims: (1) Identify and model the mechanisms of fibrous attachment toughening ex vivo. We will model and experimentally validate how disorder across length scales toughens the tendon-to-bone attachment. Hierarchical molecular dynamics-to- continuum models, enriched by machine learning, will be validated in vitro, in systems with nanoscale control of mineral distributions, and ex vivo, in tissue samples of fibrous attachments. (2) Identify and model the loss of fibrous attachment toughness due to pathologic settings in vivo using murine rotator cuff tendinopathy models. In both aims, nano- through milli-scale characterization will be performed to define the mechanisms driving mechanical behavior. We will test the hypothesis that pathology- induced changes at multiple length scales will predict changes in failure mode. These models and experiments will test the global hypothesis that energy absorption across hierarchies is a fundamental toughening mechanism by which fibrous interfaces resist injury level loads. Taken together, we believe that these new models of fibrous attachment will enable an understanding of how the order and complexity of fibrous attachments leads to effective attachment of tissues.

项目总结