scholarly journals Interplay of Forces and the Immune Response for Functional Tendon Regeneration

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuwei Yang ◽  
Yicong Wu ◽  
Ke Zhou ◽  
Dongmei Wu ◽  
Xudong Yao ◽  
...  
Keyword(s):  
Immune Response ◽  
Tensile Strength ◽  
Tendon Healing ◽  
Biomechanical Properties ◽  
Tendon Injury ◽  
Rapid Decline ◽  
Sports Activity ◽  
Tendon Regeneration ◽  
Functional Regeneration ◽  
External Forces

Tendon injury commonly occurs during sports activity, which may cause interruption or rapid decline in athletic career. Tensile strength, as one aspect of tendon biomechanical properties, is the main parameter of tendon function. Tendon injury will induce an immune response and cause the loss of tensile strength. Regulation of mechanical forces during tendon healing also changes immune response to improve regeneration. Here, the effects of internal/external forces and immune response on tendon regeneration are reviewed. The interaction between immune response and internal/external forces during tendon regeneration is critically examined and compared, in relation to other tissues. In conclusion, it is essential to maintain a fine balance between internal/external forces and immune response, to optimize tendon functional regeneration.

scholarly journals Molecular Mechanisms of Fetal Tendon Regeneration Versus Adult Fibrous Repair

2021 ◽  
Vol 22 (11) ◽  
pp. 5619
Author(s):  
Iris Ribitsch ◽  
Andrea Bileck ◽  
Alexander D. Aldoshin ◽  
Maciej M. Kańduła ◽  
Rupert L. Mayer ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Molecular Mechanisms ◽  
Unmet Need ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Inflammatory Factors ◽  
Large Animal ◽  
Post Injury ◽  
Tendon Regeneration ◽  
Large Animal Models

Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies.

scholarly journals Reprogramming adult tendon healing using regenerative neonatal regulatory T cells

2021 ◽  
Author(s):  
Varun Arvind ◽  
Kristen L Howell ◽  
Alice H Huang
Keyword(s):  
Transcriptional Profiling ◽  
Macrophage Polarization ◽  
Critical Role ◽  
Tendon Healing ◽  
Distinct Type ◽  
Clinical Problem ◽  
Tendon Regeneration ◽  
Functional Regeneration

Tendinopathy is a common clinical problem leading to significant musculoskeletal disability. Using a neonatal mouse model of tendon regeneration compared to adult tendon fibrosis, we identified a unique immune profile in regeneration that is associated with type 2 macrophage polarization and regulatory T cell (Treg) infiltration. Neonatal Treg ablation resulted in a dysregulated immune response leading to failed tenocyte recruitment and loss of functional regeneration. Transcriptional profiling of adult and neonatal tendon Tregs revealed distinct type 1 and type 2 immune signatures that facilitate macrophage polarization following injury. Finally, adoptive transfer of mouse and human neonatal Tregs was sufficient to improve functional regeneration, in contrast to adult Treg transfer. Collectively, these studies uncover a critical role for neonatal Tregs in controlling immune polarization to promote an environment permissive for tendon regeneration. Our findings provide a basis for immune modulating therapies to facilitate regenerative adult tendon healing.

Number of suture throws and its impact on the biomechanical properties of the four-strand cruciate locked flexor tendon repair with FiberWire

2012 ◽  
Vol 37 (9) ◽  
pp. 826-831 ◽  
Author(s):  
S. V. Le ◽  
S. Chiu ◽  
R. C. Meineke ◽  
P. Williams ◽  
M. D. Wongworawat
Keyword(s):  
Tensile Strength ◽  
Ultimate Tensile Strength ◽  
Flexor Tendon ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Early Mobilization ◽  
Biomechanical Properties ◽  
Optimal Number ◽  
Flexor Tendon Repair ◽  
Mode Of Failure

FiberWire is a popular suture in flexor tendon repair that allows for early mobilization, but its poor knot-holding properties have raised concerns over the potential effects on tendon healing and strength. We examined how the number of knot throws affects the 2 mm gap force, ultimate tensile strength, and mode of failure in a four-strand cruciate locked tendon repair in porcine flexor tendons in order to elucidate the optimal number of suture throws. There was no effect on the 2 mm gap force with increasing knot throws, but there was a significant increase in ultimate tensile strength. A minimum of six-knot throws prevents unravelling, whereas five out of 10 of repairs unravelled with less than six throws.

scholarly journals Scleraxis-Lineage Cell Depletion Improves Tendon Healing and Disrupts Adult Tendon Homeostasis

2020 ◽  
Author(s):  
Katherine T. Best ◽  
Antonion Korcari ◽  
Keshia E. Mora ◽  
Emma Knapp ◽  
Mark R. Buckley ◽  
...  
Keyword(s):  
Tendon Repair ◽  
Tendon Healing ◽  
Biomechanical Properties ◽  
Tendon Injury ◽  
Cell Depletion ◽  
Cytoskeletal Organization ◽  
Cell Localization ◽  
Fundamental Understanding ◽  
Injury And Repair ◽  
Fibril Diameter

AbstractDespite the requirement for Scleraxis-lineage (ScxLin) cells during tendon development, the function of ScxLin cells during adult tendon repair, post-natal growth, and adult homeostasis have not been defined. Therefore, we inducibly depleted ScxLin cells (ScxLinDTR) prior to tendon injury and repair surgery and hypothesized that ScxLinDTR mice would exhibit functionally deficient healing compared to wildtype littermates. Surprisingly, depletion of ScxLin cells resulted in increased biomechanical properties without impairments in gliding function at 28 days post-repair, indicative of regeneration. RNA sequencing of day 28 post-repair tendons highlighted differences in matrix-related genes, cell motility, cytoskeletal organization, and metabolism. We also utilized ScxLinDTR mice to define the effects on post-natal tendon growth and adult tendon homeostasis and discovered that adult ScxLin cell depletion resulted in altered tendon collagen fibril diameter, density, and dispersion. Collectively, these findings enhance our fundamental understanding of tendon cell localization, function, and fate during healing, growth, and homeostasis.

scholarly journals Scleraxis-lineage cell depletion improves tendon healing and disrupts adult tendon homeostasis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Katherine T Best ◽  
Antonion Korcari ◽  
Keshia E Mora ◽  
Anne EC Nichols ◽  
Samantha N Muscat ◽  
...  
Keyword(s):  
Tendon Repair ◽  
Tendon Healing ◽  
Biomechanical Properties ◽  
Tendon Injury ◽  
Cell Depletion ◽  
Cytoskeletal Organization ◽  
Cell Localization ◽  
Fundamental Understanding ◽  
Injury And Repair ◽  
Fibril Diameter

Despite the requirement for Scleraxis-lineage (ScxLin) cells during tendon development, the function of ScxLin cells during adult tendon repair, post-natal growth, and adult homeostasis have not been defined. Therefore, we inducibly depleted ScxLin cells (ScxLinDTR) prior to tendon injury and repair surgery and hypothesized that ScxLinDTR mice would exhibit functionally deficient healing compared to wild-type littermates. Surprisingly, depletion of ScxLin cells resulted in increased biomechanical properties without impairments in gliding function at 28 days post-repair, indicative of regeneration. RNA sequencing of day 28 post-repair tendons highlighted differences in matrix-related genes, cell motility, cytoskeletal organization, and metabolism. We also utilized ScxLinDTR mice to define the effects on post-natal tendon growth and adult tendon homeostasis and discovered that adult ScxLin cell depletion resulted in altered tendon collagen fibril diameter, density, and dispersion. Collectively, these findings enhance our fundamental understanding of tendon cell localization, function, and fate during healing, growth, and homeostasis.

scholarly journals Macrophage depletion impairs neonatal tendon regeneration

2021 ◽  
Author(s):  
Kristen L Howell ◽  
Deepak A Kaji ◽  
Angela Montero ◽  
Kenji Yeoh ◽  
Philip Nasser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Cell Proliferation ◽  
Immune Cells ◽  
Tendon Healing ◽  
Connective Tissues ◽  
Tgfβ Signaling ◽  
Tendon Regeneration ◽  
Macrophage Depletion ◽  
Macrophage Chemotaxis

Tendons are dense connective tissues that transmit muscle forces to the skeleton. After adult injury, healing potential is generally poor and dominated by scar formation. Although the immune response is a key feature of healing, the specific immune cells and signals that drive tendon healing have not been fully defined. In particular, the immune regulators underlying tendon regeneration are almost completely undetermined due to a paucity of tendon regeneration models. Using a mouse model of neonatal tendon regeneration, we screened for immune-related markers and identified upregulation of several genes associated with inflammation, macrophage chemotaxis, and TGFβ signaling after injury. Depletion of macrophages using AP20187 treatment of MaFIA mice resulted in impaired functional healing, reduced cell proliferation, reduced ScxGFP+ neo-tendon formation, and altered tendon gene expression. Collectively, these results show that inflammation is a key component of neonatal tendon regeneration and demonstrate a requirement for macrophages in effective functional healing. 

scholarly journals Platelet-Rich Plasma Releasate Promotes Early Healing in Tendon After Acute Injury

2021 ◽  
Vol 9 (4) ◽  
pp. 232596712199037
Author(s):  
Tung-Yang Yu ◽  
Jong-Hwei S. Pang ◽  
Li-Ping Lin ◽  
Ju-Wen Cheng ◽  
Shih-Jung Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tensile Strength ◽  
Achilles Tendon ◽  
Platelet Rich Plasma ◽  
Testing Machine ◽  
Tendon Healing ◽  
Tendon Injury ◽  
The Other ◽  
Acute Injury ◽  
Early Healing

Background: Acute tendon injury can limit motion and thereby inhibit tendon healing. Positive results have been found after the use of platelet-rich plasma (PRP) to treat tendon injury; however, the early effects of PRP on tendon regeneration are not known. Purpose/Hypothesis: The purpose of this study was to evaluate the effects of PRP releasate (PRPr) on the early stages of tendon healing in a rat partial tenotomy model. It was hypothesized that PRPr can promote early healing of an Achilles tendon in rats. Study Design: Controlled laboratory study. Methods: PRP was prepared by a 2-step method of manual platelet concentration from 10 rats. PRPr was isolated from the clotted preparation after activation by thrombin and was applied to an Achilles tendon on 1 side of 30 rats on the second day after partial tenotomy, with normal saline used as the control on the other side. Achilles tendon samples were harvested 5 and 10 days after tenotomy. At each time point, 15 Achilles tendon samples were obtained, of which 5 samples were evaluated by Masson trichrome staining, apoptosis, and cell proliferation, while the other 10 samples were tested for tensile strength using a material testing machine. Results: Compared with saline-treated control tendons, the PRPr-treated tendons showed increased collagen synthesis near the cut edge and fewer apoptotic cells ( P = .01). An immunohistochemical analysis revealed more Ki-67–positive cells but fewer cluster of differentiation (CD) 68+ (ED1+) macrophages in PRPr tendons compared with saline-treated tendons ( P < .01). Tendons treated with PRPr also showed higher ultimate tensile strength than those treated with saline ( P = .03). Conclusion: PRPr treatment promotes tissue recovery in the early phase of tendon healing by stimulating tendon cell proliferation and collagen production while inhibiting cell apoptosis and CD68+ (ED1+) macrophage infiltration. Clinical Relevance: These findings suggest that with PRPr treatment, higher loads can be applied to the healing tendon at an earlier time, which can help the patient resume activity earlier.

scholarly journals Neutralization of SARS-CoV-2 with IgG from COVID-19-convalescent plasma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kenji Maeda ◽  
Nobuyo Higashi-Kuwata ◽  
Noriko Kinoshita ◽  
Satoshi Kutsuna ◽  
Kiyoto Tsuchiya ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Utility ◽  
Plasma Sample ◽  
Temporal Changes ◽  
Rapid Decline ◽  
Multiple Endpoints ◽  
Neutralization Activity ◽  
Neutralizing Activity ◽  
Binding Antibody ◽  
Potent Immune Response

AbstractWhile there are various attempts to administer COVID-19-convalescent plasmas to SARS-CoV-2-infected patients, neither appropriate approach nor clinical utility has been established. We examined the presence and temporal changes of the neutralizing activity of IgG fractions from 43 COVID-19-convalescent plasmas using cell-based assays with multiple endpoints. IgG fractions from 27 cases (62.8%) had significant neutralizing activity and moderately to potently inhibited SARS-CoV-2 infection in cell-based assays; however, no detectable neutralizing activity was found in 16 cases (37.2%). Approximately half of the patients (~ 41%), who had significant neutralizing activity, lost the neutralization activity within ~ 1 month. Despite the rapid decline of neutralizing activity in plasmas, good amounts of SARS-CoV-2-S1-binding antibodies were persistently seen. The longer exposure of COVID-19 patients to greater amounts of SARS-CoV-2 elicits potent immune response to SARS-CoV-2, producing greater neutralization activity and SARS-CoV-2-S1-binding antibody amounts. The dilution of highly-neutralizing plasmas with poorly-neutralizing plasmas relatively readily reduced neutralizing activity. The presence of good amounts of SARS-CoV-2-S1-binding antibodies does not serve as a surrogate ensuring the presence of good neutralizing activity. In selecting good COVID-19-convalescent plasmas, quantification of neutralizing activity in each plasma sample before collection and use is required.

scholarly journals Functional regeneration and repair of tendons using biomimetic scaffolds loaded with recombinant periostin

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yu Wang ◽  
Shanshan Jin ◽  
Dan Luo ◽  
Danqing He ◽  
Chunyan Shi ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Transcriptional Profiling ◽  
Collagen Scaffold ◽  
Defect Model ◽  
Tendon Regeneration ◽  
Biomimetic Scaffolds ◽  
Functional Regeneration

AbstractTendon injuries disrupt the balance between stability and mobility, causing compromised functions and disabilities. The regeneration of mature, functional tendons remains a clinical challenge. Here, we perform transcriptional profiling of tendon developmental processes to show that the extracellular matrix-associated protein periostin (Postn) contributes to the maintenance of tendon stem/progenitor cell (TSPC) functions and promotes tendon regeneration. We show that recombinant periostin (rPOSTN) promotes the proliferation and stemness of TSPCs, and maintains the tenogenic potentials of TSPCs in vitro. We also find that rPOSTN protects TSPCs against functional impairment during long-term passage in vitro. For in vivo tendon formation, we construct a biomimetic parallel-aligned collagen scaffold to facilitate TSPC tenogenesis. Using a rat full-cut Achilles tendon defect model, we demonstrate that scaffolds loaded with rPOSTN promote endogenous TSPC recruitment, tendon regeneration and repair with native-like hierarchically organized collagen fibers. Moreover, newly regenerated tendons show recovery of mechanical properties and locomotion functions.

Comparison of healing in forelimb and hindlimb surgically induced core lesions of the equine superficial digital flexor tendon

2014 ◽  
Vol 27 (05) ◽  
pp. 358-365 ◽  
Author(s):  
P. R. Van Weeren ◽  
C. H. A. Van de Lest ◽  
J. Boere ◽  
M. Reyes ◽  
J. C. Ionita ◽  
...  
Keyword(s):  
Doppler Ultrasound ◽  
Clinical Relevance ◽  
Flexor Tendon ◽  
Healing Process ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Colour Doppler ◽  
Post Surgery ◽  
Superficial Digital Flexor Tendon ◽  
Surgically Induced

SummaryObjective: Even though equine multi-limb tendinopathy models have been reported, it is unknown if fore- and hindlimb tendon healing behave similarly. The aim of this study was to compare the healing process of surgically induced superficial digital flexor tendon (SDFT) core lesions of fore- and hindlimbs in horses.Methods: Tendon core lesions were surgically induced in the SDFT of both fore- and hindlimbs in eight horses. One randomly assigned forelimb and one randomly assigned hindlimb were injected with saline one and two weeks post-surgery. The healing process was monitored clinically and ultrasonographically. After 24 weeks, the tendons were harvested and biochemical, biomechanical and histological parameters were evaluated.Results: Twenty-four weeks post-surgery, the forelimb SDFT lesions had a significantly higher colour Doppler ultrasound vascularization score (p = 0.02) and glycosaminoglycan concentration (p = 0.04) and a significantly lower hydroxylysylpyridinoline content (p = 0.03).Clinical relevance: Our results indicate that fore- and hindlimb SDFT surgically induced lesions exhibit significant differences in several important parameters of tendon healing 24 weeks post-surgery. These differences create significant challenges in using all four limbs and accurately interpreting the results that one might generate. Therefore these findings do not support the use of four-limb models for study of tendon injury until the reasons for these differences are much better understood.

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