Models of tendon development and injury

Theodossiou, Sophia K.; Schiele, Nathan R.

doi:10.1186/s42490-019-0029-5

Cited by 24 publications

(17 citation statements)

References 180 publications

(292 reference statements)

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“…Despite these findings, mechanistic studies are difficult to perform in patients, which typically present in the late stages of disease progression and have complex health histories. Genetically modified organisms, such as the mouse, provide an extensive toolkit of engineered systems to better define the role of various molecular mechanisms 17 . Therefore, our objective was to generate and compare murine models of rotator cuff pathology by inducing pathologic joint loading environments.…”

Section: Introductionmentioning

confidence: 99%

The role of loading in murine models of rotator cuff disease

Abraham

Fang

Golman

et al. 2021

Journal Orthopaedic Research

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Rotator cuff disease pathogenesis is associated with intrinsic (e.g., age, joint laxity, muscle weakness) and extrinsic (e.g., mechanical load, fatigue) factors that lead to chronic degeneration of the cuff tissues. However, etiological studies are difficult to perform in patients due to the long duration of disease onset and progression. Therefore, the purpose of this study was to determine the effects of altered joint loading on the rotator cuff. Mice were subjected to one of three load‐dependent rotator cuff tendinopathy models: underuse loading, achieved by injecting botulinum toxin‐A into the supraspinatus muscle; overuse loading, achieved using downhill treadmill running; destabilization loading, achieved by surgical excision of the infraspinatus tendon. All models were compared to cage activity animals. Whole joint function was assessed longitudinally using gait analysis. Tissue‐scale structure and function were determined using microCT, tensile testing, and histology. The molecular response of the supraspinatus tendon and enthesis was determined by measuring the expression of 84 wound healing‐associated genes. Underuse and destabilization altered forepaw weight‐bearing, decreased tendon‐to‐bone attachment strength, decreased mineral density of the humeral epiphysis, and reduced tendon strength. Transcriptional activity of the underuse group returned to baseline levels by 4 weeks, while destabilization had significant upregulation of inflammation, growth factors, and extracellular matrix remodeling genes. Surprisingly, overuse activity caused changes in walking patterns, increased tendon stiffness, and primarily suppressed expression of wound healing‐related genes. In summary, the tendinopathy models demonstrated how divergent muscle loading can result in clinically relevant alterations in rotator cuff structure, function, and gene expression.

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Section: Introductionmentioning

confidence: 99%

The role of loading in murine models of rotator cuff disease

Abraham

Fang

Golman

et al. 2021

Journal Orthopaedic Research

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“…However, the precise magnitude, frequency, and duration of stimulation required for normal tendon homeostasis remain unknown. In addition, despite numerous in vivo , in vitro , and ex vivo studies on tendon mechanical properties and the development of prediction models ( Galloway et al, 2013 ; Fang and Lake, 2016 ; Herod et al, 2016 ; Thorpe and Screen, 2016 ; Thompson et al, 2017 ; Chen et al, 2018 ; Carniel and Fancello, 2019 ; Theodossiou and Schiele, 2019 ), the precise in vivo loading levels required to induce tendon repair are yet unspecified. In this regard, further understanding of the in vivo loading of tendons is vital to understand the mechanobiological stimuli required to induce anabolic or reduce catabolic activity ( Lavagnino et al, 2015 ).…”

Section: Optimization Of Type I Collagen-based Scaffolds For the Development Of Specific Tissue Substitutesmentioning

confidence: 99%

Mimicking the Hierarchical Organization of Natural Collagen: Toward the Development of Ideal Scaffolding Material for Tissue Regeneration

Salvatore

Gallo

Natali

et al. 2021

Front. Bioeng. Biotechnol.

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Biological materials found in living organisms, many of which are proteins, feature a complex hierarchical organization. Type I collagen, a fibrous structural protein ubiquitous in the mammalian body, provides a striking example of such a hierarchical material, with peculiar architectural features ranging from the amino acid sequence at the nanoscale (primary structure) up to the assembly of fibrils (quaternary structure) and fibers, with lengths of the order of microns. Collagen plays a dominant role in maintaining the biological and structural integrity of various tissues and organs, such as bone, skin, tendons, blood vessels, and cartilage. Thus, “artificial” collagen-based fibrous assemblies, endowed with appropriate structural properties, represent ideal substrates for the development of devices for tissue engineering applications. In recent years, with the ultimate goal of developing three-dimensional scaffolds with optimal bioactivity able to promote both regeneration and functional recovery of a damaged tissue, numerous studies focused on the capability to finely modulate the scaffold architecture at the microscale and the nanoscale in order to closely mimic the hierarchical features of the extracellular matrix and, in particular, the natural patterning of collagen. All of these studies clearly show that the accurate characterization of the collagen structure at the submolecular and supramolecular levels is pivotal to the understanding of the relationships between the nanostructural/microstructural properties of the fabricated scaffold and its macroscopic performance. Several studies also demonstrate that the selected processing, including any crosslinking and/or sterilization treatments, can strongly affect the architecture of collagen at various length scales. The aim of this review is to highlight the most recent findings on the development of collagen-based scaffolds with optimized properties for tissue engineering. The optimization of the scaffolds is particularly related to the modulation of the collagen architecture, which, in turn, impacts on the achieved bioactivity.

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“…Many reviews focus in-depth on the history of understanding matrix turnover, tendon biomechanics, and the methods/models used to understand tendon as well as ligament mechanobiology (Lavagnino et al, 2015;Thomopoulos et al, 2015;Wang and Chen, 2018;Dyment et al, 2020;Friese et al, 2020;Gracey et al, 2020;Wang et al, 2020;Bramson et al, 2021). In addition, in vivo models of tendon degeneration are the focus of another review (Theodossiou and Schiele, 2019). This review summarizes the more recent findings relating to tendon mechanobiology using various model systems.…”

Section: Evaluation Of Model Systemsmentioning

confidence: 99%

Dynamic Load Model Systems of Tendon Inflammation and Mechanobiology

Benage

Sweeney

Giers

et al. 2022

Front. Bioeng. Biotechnol.

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Dynamic loading is a shared feature of tendon tissue homeostasis and pathology. Tendon cells have the inherent ability to sense mechanical loads that initiate molecular-level mechanotransduction pathways. While mature tendons require physiological mechanical loading in order to maintain and fine tune their extracellular matrix architecture, pathological loading initiates an inflammatory-mediated tissue repair pathway that may ultimately result in extracellular matrix dysregulation and tendon degeneration. The exact loading and inflammatory mechanisms involved in tendon healing and pathology is unclear although a precise understanding is imperative to improving therapeutic outcomes of tendon pathologies. Thus, various model systems have been designed to help elucidate the underlying mechanisms of tendon mechanobiology via mimicry of the in vivo tendon architecture and biomechanics. Recent development of model systems has focused on identifying mechanoresponses to various mechanical loading platforms. Less effort has been placed on identifying inflammatory pathways involved in tendon pathology etiology, though inflammation has been implicated in the onset of such chronic injuries. The focus of this work is to highlight the latest discoveries in tendon mechanobiology platforms and specifically identify the gaps for future work. An interdisciplinary approach is necessary to reveal the complex molecular interplay that leads to tendon pathologies and will ultimately identify potential regenerative therapeutic targets.

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Models of tendon development and injury

Cited by 24 publications

References 180 publications

The role of loading in murine models of rotator cuff disease

The role of loading in murine models of rotator cuff disease

Mimicking the Hierarchical Organization of Natural Collagen: Toward the Development of Ideal Scaffolding Material for Tissue Regeneration

Dynamic Load Model Systems of Tendon Inflammation and Mechanobiology

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