Method development and characterization of chick embryo tendon mechanical properties

Navarro, Javier; Korcari, Antonion; Nguyen, Phong K.; Bah, Ibrahima; AlKhalifa, Abdulrahman; Fink, Spencer; Buckley, Mark R.; Kuo, Catherine K.

doi:10.1016/j.jbiomech.2022.110970

Cited by 11 publications

(25 citation statements)

References 56 publications

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“…Our previous work showed tensile modulus and nanoscale modulus both increase as a function of developmental stage (Marturano et al, 2013;Navarro et al, 2022). Here, we treated tendon explants with rLOX and used AFM to measure changes in the values and spatial distribution of nanoscale moduli.…”

Section: Discussionmentioning

confidence: 98%

“…In particular, 2X and 5X rLOX treatment of HH43 tendons led to an elastic modulus that was 280% higher than with control treatment (Figure 6). For comparison, normally developing tendon increases its elastic modulus 300% from HH43 to HH45 (the chick embryo hatches after HH45) (Navarro et al, 2022). It is also possible that rLOX induced cell behaviors that regulated, partially or wholly, the increases and plateau in tendon mechanical properties.…”

Section: Discussionmentioning

confidence: 99%

“…Tendons treated in vivo with either vehicle or rLOX were harvested and tensile tested as previously described (Navarro et al, 2022). Briefly, tendons were gripped at each end and stretched uniaxially at 1% strain per second until failure.…”

Section: Tensile Mechanical Testing and Data Analysismentioning

confidence: 99%

“…Calcaneal tendons of HH40 and HH43 chick embryos were dissected out of the limb, using our previously established protocol to ensure muscle and fibrocartilage were excluded (Navarro et al, 2022). After the tendon was separated from the limb, tendon bundles separated easily from each other during gentle extraction using fine tweezers.…”

Section: Ex Ovo Explant Culturementioning

confidence: 99%

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Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment

Nguyen

Jana

Huang

et al. 2022

Front. Bioeng. Biotechnol.

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Tendon mechanical properties are significantly compromised in adult tendon injuries, tendon-related birth defects, and connective tissue disorders. Unfortunately, there currently is no effective treatment to restore native tendon mechanical properties after postnatal tendon injury or abnormal fetal development. Approaches to promote crosslinking of extracellular matrix components in tendon have been proposed to enhance insufficient mechanical properties of fibrotic tendon after healing. However, these crosslinking agents, which are not naturally present in the body, are associated with toxicity and significant reductions in metabolic activity at concentrations that enhance tendon mechanical properties. In contrast, we propose that an effective method to restore tendon mechanical properties would be to promote lysyl oxidase (LOX)-mediated collagen crosslinking in tendon during adult tissue healing or fetal tissue development. LOX is naturally occurring in the body, and we previously demonstrated LOX-mediated collagen crosslinking to be a critical regulator of tendon mechanical properties during new tissue formation. In this study, we examined the effects of recombinant LOX treatment on tendon at different stages of development. We found that recombinant LOX treatment significantly enhanced tensile and nanoscale tendon mechanical properties without affecting cell viability or collagen content, density, and maturity. Interestingly, both tendon elastic modulus and LOX-mediated collagen crosslink density plateaued at higher recombinant LOX concentrations, which may have been due to limited availability of adjacent lysine residues that are near enough to be crosslinked together. The plateau in crosslink density at higher concentrations of recombinant LOX treatments may have implications for preventing over-stiffening of tendon, though this requires further investigation. These findings demonstrate the exciting potential for a LOX-based therapeutic to enhance tendon mechanical properties via a naturally occurring crosslinking mechanism, which could have tremendous implications for an estimated 32 million acute and chronic tendon and ligament injuries each year in the U.S.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Tensile Mechanical Testing and Data Analysismentioning

confidence: 99%

Section: Ex Ovo Explant Culturementioning

confidence: 99%

See 2 more Smart Citations

Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment

Nguyen

Jana

Huang

et al. 2022

Front. Bioeng. Biotechnol.

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“…The tendon was periodically submerged in PBS to avoid any potential tissue drying. Next, gripped tendons were transferred into a semi-customized uniaxial microtester (eXpert 4000 MicroTester, ADMET, Inc., Norwood MA) [21][22][23][24]. The microtester was transferred to an inverted microscope (Olympus BX51, Olympus) to visualize the tendon and quantify the gauge length, width, and thickness.…”

Section: Quantification Of Biomechanical Propertiesmentioning

confidence: 99%

Inducible depletion of Scleraxis-lineage cells during tendon healing impairs multi-scale restoration of tendon structure

Korcari

Muscat

Buckley

et al. 2022

Preprint

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Tendons are composed of a heterogeneous cell environment, with Scleraxis-lineage (ScxLin) cells being the predominant population. Although ScxLin cells are required for maintenance of tendon homeostasis, their functions during tendon healing are unknown. To this end, we first characterized the spatiotemporal dynamics of ScxLin cells during tendon healing, and identified that the overall ScxLin pool continuously expands up to early remodeling healing phase. To better define the function of ScxLin cells during the late proliferative phase of healing, we inducibly depleted ScxLin cells from day 14-18 post-surgery using the Scx-Cre; Rosa-DTR mouse model, with local administration of diphtheria toxin inducing apoptosis of ScxLin cells in the healing tendon. At D28 post-surgery, ScxLin cell depleted tendons (DTR) had substantial impairments in structure and function, relative to WT, demonstrating the importance of ScxLin cells during tendon healing. Next, bulk RNAseq was utilized to identify the underlying mechanisms that were impaired with depletion and revealed that ScxLin depletion induced molecular and morphological stagnation of the healing process at D28. However, this stagnation was transient, such that by D56 tendon mechanics in DTR were not significantly different than wildtype repairs. Collectively, these data offer fundamental knowledge on the dynamics and roles of ScxLin cells during tendon healing.

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Histological and immunohistochemical guide to tendon tissue

Chatterjee

Evans

Bell

et al. 2023

Journal Orthopaedic Research

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Tendons are unique dense connective tissues with discrete zones having specific structure and function. They are juxtaposed with other tissues (e.g., bone, muscle, and fat) with different compositional, structural, and mechanical properties. Additionally, tendon properties change drastically with growth and development, disease, aging, and injury. Consequently, there are unique challenges to performing high quality histological assessment of this tissue. To address this need, histological assessment was one of the breakout session topics at the 2022 Orthopaedic Research Society (ORS) Tendon Conference hosted at the University of Pennsylvania. The purpose of the breakout session was to discuss needs from members of the ORS Tendon Section related to histological procedures, data presentation, knowledge dissemination, and guidelines for future work. Therefore, this review provides a brief overview of the outcomes of this discussion and provides a set of guidelines, based on the perspectives from our laboratories, for histological assessment to assist researchers in their quest to utilize these techniques to enhance the outcomes and interpretations of their studies.

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Method development and characterization of chick embryo tendon mechanical properties

Cited by 11 publications

References 56 publications

Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment

Tendon mechanical properties are enhanced via recombinant lysyl oxidase treatment

Inducible depletion of Scleraxis-lineage cells during tendon healing impairs multi-scale restoration of tendon structure

Histological and immunohistochemical guide to tendon tissue

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