scholarly journals Tumour DDR1 promotes collagen fibre alignment to instigate immune exclusion

Nature ◽  
2021 ◽  
Author(s):  
Xiujie Sun ◽  
Bogang Wu ◽  
Huai-Chin Chiang ◽  
Hui Deng ◽  
Xiaowen Zhang ◽  
...  
Keyword(s):  
Collagen Fibre ◽  
Fibre Alignment ◽  
Immune Exclusion

Collagen fibre alignment in the human preauricular dermis before and after rhytidectomy: A sem study

1985 ◽  
Vol 17 (2) ◽  
pp. 164
Author(s):  
D. Levanon ◽  
J. Govrin-Yehudain ◽  
B. Hirshowitz
Keyword(s):  
Collagen Fibre ◽  
Fibre Alignment ◽  
Sem Study ◽  
Before And After

scholarly journals Tissue loading and microstructure regulate the deformation of embedded nerve fibres: predictions from single-scale and multiscale simulations

2017 ◽  
Vol 14 (135) ◽  
pp. 20170326 ◽  
Author(s):  
Vahhab Zarei ◽  
Sijia Zhang ◽  
Beth A. Winkelstein ◽  
Victor H. Barocas
Keyword(s):  
Volume Concentration ◽  
Collagen Fibre ◽  
Axial Loading ◽  
Multiscale Simulations ◽  
Nerve Fibres ◽  
Fibre Alignment ◽  
Fibre Network ◽  
Single Scale ◽  
Cause Of Pain ◽  
Transverse Axial

Excessive deformation of nerve fibres (axons) in the spinal facet capsular ligaments (FCLs) can be a cause of pain. The axons are embedded in the fibrous extracellular matrix (ECM) of FCLs, so understanding how local fibre organization and micromechanics modulate their mechanical behaviour is essential. We constructed a computational discrete-fibre model of an axon embedded in a collagen fibre network attached to the axon by distinct fibre–axon connections. This model was used to relate the axonal deformation to the fibre alignment and collagen volume concentration of the surrounding network during transverse, axial and shear deformations. Our results showed that fibre alignment affects axonal deformation only during transverse and axial loading, but higher collagen volume concentration results in larger overall axonal strains for all loading cases. Furthermore, axial loading leads to the largest stretch of axonal microtubules and induces the largest forces on axon's surface in most cases. Comparison between this model and a multiscale continuum model for a representative case showed that although both models predicted similar averaged axonal strains, strain was more heterogeneous in the discrete-fibre model.

scholarly journals Stretch-induced network reconfiguration of collagen fibres in the human facet capsular ligament

2016 ◽  
Vol 13 (114) ◽  
pp. 20150883 ◽  
Author(s):  
Sijia Zhang ◽  
Danielle S. Bassett ◽  
Beth A. Winkelstein
Keyword(s):  
Community Structure ◽  
Polarized Light ◽  
Collagen Fibre ◽  
Chronic Neck Pain ◽  
Common Source ◽  
Network Reconfiguration ◽  
Collagen Fibres ◽  
Capsular Ligament ◽  
Fibre Alignment ◽  
External Forces

Biomaterials can display complex spatial patterns of cellular responses to external forces. Revealing and predicting the role of these patterns in material failure require an understanding of the statistical dependencies between spatially distributed changes in a cell's local biomechanical environment, including altered collagen fibre kinematics in the extracellular matrix. Here, we develop and apply a novel extension of network science methods to investigate how excessive tensile stretch of the human cervical facet capsular ligament (FCL), a common source of chronic neck pain, affects the local reorganization of collagen fibres. We define collagen alignment networks based on similarity in fibre alignment angles measured by quantitative polarized light imaging. We quantify the reorganization of these networks following macroscopic loading by describing the dynamic reconfiguration of network communities, regions of the material that display similar fibre alignment angles. Alterations in community structure occur smoothly over time, indicating coordinated adaptation of fibres to loading. Moreover, flexibility, a measure of network reconfiguration, tracks the loss of FCL's mechanical integrity at the onset of anomalous realignment (AR) and regions of AR display altered community structure. These findings use novel network-based techniques to explain abnormal collagen fibre reorganization, a dynamic and coordinated multivariate process underlying tissue failure.

Online monitoring of collagen fibre alignment in tissue-engineered tendon by PSOCT

2008 ◽  
Vol 2 (8) ◽  
pp. 521-524 ◽  
Author(s):  
Mark Ahearne ◽  
Pierre O. Bagnaninchi ◽  
Ying Yang ◽  
Alicia J. El Haj
Keyword(s):  
Online Monitoring ◽  
Collagen Fibre ◽  
Fibre Alignment

scholarly journals Scleraxis expressing scleral cells respond to inflammatory stimulation

2021 ◽  
Author(s):  
Ghada Atta ◽  
Falk Schroedl ◽  
Alexandra Kaser-Eichberger ◽  
Gabriel Spitzer ◽  
Andreas Traweger ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Interleukin 1 ◽  
Collagen Fibre ◽  
Tissue Growth ◽  
Collagen Degradation ◽  
Ocular Tissue ◽  
Marker Genes ◽  
Ex Vivo Model ◽  
Tendon Cell ◽  
Fibre Degradation

AbstractThe sclera is an ocular tissue rich of collagenous extracellular matrix, which is built up and maintained by relatively few, still poorly characterized fibroblast-like cells. The aims of this study are to add to the characterization of scleral fibroblasts and to examine the reaction of these fibroblasts to inflammatory stimulation in an ex vivo organotypic model. Scleras of scleraxis-GFP (SCX-GFP) mice were analyzed using immunohistochemistry and qRT-PCR for the expression of the tendon cell associated marker genes scleraxis (SCX), mohawk and tenomodulin. In organotypic tissue culture, explanted scleras of adult scleraxis GFP reporter mice were exposed to 10 ng/ml recombinant interleukin 1-ß (IL1-ß) and IL1-ß in combination with dexamethasone. The tissue was then analyzed by immunofluorescence staining of the inflammation- and fibrosis-associated proteins IL6, COX-2, iNOS, connective tissue growth factor, MMP2, MMP3, and MMP13 as well as for collagen fibre degradation using a Collagen Hybridizing Peptide (CHP) binding assay. The mouse sclera displayed a strong expression of scleraxis promoter-driven GFP, indicating a tendon cell-like phenotype, as well as expression of scleraxis, tenomodulin and mohawk mRNA. Upon IL1-ß stimulation, SCX-GFP+ cells significantly upregulated the expression of all proteins analysed. Moreover, IL1-ß stimulation resulted in significant collagen degradation. Adding the corticosteroid dexamethasone significantly reduced the response to IL1-ß stimulation. Collagen degradation was significantly enhanced in the IL1-ß group. Dexamethasone demonstrated a significant rescue effect. This work provides insights into the characteristics of scleral cells and establishes an ex vivo model of scleral inflammation.

scholarly journals Heat impact during laser ablation extraction of mineralised tissue micropillars

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samuel McPhee ◽  
Alexander Groetsch ◽  
Jonathan D. Shephard ◽  
Uwe Wolfram
Keyword(s):  
Laser Ablation ◽  
Mechanical Testing ◽  
Laser Scanning ◽  
Pulsed Laser ◽  
Temperature Response ◽  
Collagen Fibre ◽  
Pulsed Laser Ablation ◽  
Collagen Molecules ◽  
Ultrashort Pulsed Laser ◽  
The Impact

AbstractThe underlying constraint of ultrashort pulsed laser ablation in both the clinical and micromachining setting is the uncertainty regarding the impact on the composition of material surrounding the ablated region. A heat model representing the laser-tissue interaction was implemented into a finite element suite to assess the cumulative temperature response of bone during ultrashort pulsed laser ablation. As an example, we focus on the extraction of mineralised collagen fibre micropillars. Laser induced heating can cause denaturation of the collagen, resulting in ultrastructural loss which could affect mechanical testing results. Laser parameters were taken from a used micropillar extraction protocol. The laser scanning pattern consisted of 4085 pulses, with a final radial pass being 22 $$\upmu {\text {m}}$$ μ m away from the micropillar. The micropillar temperature was elevated to 70.58 $$^{\circ }{\text {C}}$$ ∘ C , remaining 79.42 $$^{\circ }{\text {C}}$$ ∘ C lower than that of which we interpret as an onset for denaturation. We verified the results by means of Raman microscopy and Energy Dispersive X-ray Microanalysis and found the laser-material interaction had no effect on the collagen molecules or mineral nanocrystals that constitute the micropillars. We, thus, show that ultrashort pulsed laser ablation is a safe and viable tool to fabricate bone specimens for mechanical testing at the micro- and nanoscale and we provide a computational model to efficiently assess this.

scholarly journals Pathways of immune exclusion in metastatic osteosarcoma are associated with inferior patient outcomes

2021 ◽  
Vol 9 (5) ◽  
pp. e001772
Author(s):  
John A Ligon ◽  
Woonyoung Choi ◽  
Gady Cojocaru ◽  
Wei Fu ◽  
Emily Han-Chung Hsiue ◽  
...  
Keyword(s):  
T Cell ◽  
Patient Outcomes ◽  
Immune Checkpoint ◽  
Tumor Antigens ◽  
Current Therapy ◽  
Normal Lung ◽  
Primary Bone Tumors ◽  
Metastatic Osteosarcoma ◽  
Immune Exclusion ◽  
Successful Immunotherapy

BackgroundCurrent therapy for osteosarcoma pulmonary metastases (PMs) is ineffective. The mechanisms that prevent successful immunotherapy in osteosarcoma are incompletely understood. We investigated the tumor microenvironment of metastatic osteosarcoma with the goal of harnessing the immune system as a therapeutic strategy.Methods66 osteosarcoma tissue specimens were analyzed by immunohistochemistry (IHC) and immune markers were digitally quantified. Tumor-infiltrating lymphocytes (TILs) from 25 specimens were profiled by functional cytometry. Comparative transcriptomic studies of distinct tumor-normal lung ‘PM interface’ and ‘PM interior’ regions from 16 PMs were performed. Clinical follow-up (median 24 months) was available from resection.ResultsIHC revealed a statistically significantly higher concentration of TILs expressing immune checkpoint and immunoregulatory molecules in PMs compared with primary bone tumors (including programmed cell death 1 (PD-1), programmed death ligand 1 (PD-L1), lymphocyte-activation gene 3 (LAG-3), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), and indoleamine 2,3-dioxygenase (IDO1). Remarkably, these lymphocytes are excluded at the PM interface compared with PM interior. TILs from PMs exhibited significantly higher amounts of PD-1 and LAG-3 and functional cytokines including interferon-γ (IFNγ) by flow cytometry. Gene expression profiling further confirmed the presence of CD8 and CD4 lymphocytes concentrated at the PM interface, along with upregulation of immunoregulatory molecules and IFNγ-driven genes in the same region. We further discovered a strong alternatively activated macrophage signature throughout the entire PMs along with a polymorphonuclear myeloid-derived suppressor cell signature focused at the PM interface. Expression of PD-L1, LAG-3, and colony-stimulating factor 1 receptor (CSF1R) at the PM interface was associated with significantly worse progression-free survival (PFS), while gene sets indicative of productive T cell immune responses (CD8 T cells, T cell survival, and major histocompatibility complex class 1 expression) were associated with significantly improved PFS.ConclusionsOsteosarcoma PMs exhibit immune exclusion characterized by the accumulation of TILs at the PM interface. These TILs produce effector cytokines, suggesting their capability of activation and recognition of tumor antigens. Our findings suggest cooperative immunosuppressive mechanisms in osteosarcoma PMs including immune checkpoint molecule expression and the presence of immunosuppressive myeloid cells. We identify cellular and molecular signatures that are associated with patient outcomes, which could be exploited for successful immunotherapy.

The Relationship of Width, Thickness, Volume and Load to Extension for Human Skin in Vitro

1980 ◽  
Vol 9 (4) ◽  
pp. 179-183 ◽  
Author(s):  
H L Stark ◽  
A Al-Haboubi
Keyword(s):  
Human Skin ◽  
Collagen Fibre ◽  
Phase Volume ◽  
Lateral Contraction ◽  
Low Stiffness ◽  
Phase Thickness ◽  
Relationship Of ◽  
The Relationship ◽  
Fibre Matrix

The relationships of width, thickness, volume and load to extension for human skin in vitro are reported. The specimens tested exhibited a low stiffness phase followed by a high stiffness phase. Volume rose than fell back to the initial volume at approximately the end of the low stiffness phase, and continued on falling to a final reduction of about 20 per cent at failure. Width decreased throughout, showing a maximum rate of reduction at approximately the end of the low stiffness phase. Thickness increased at a rate which also was maximum at the end of the low stiffness phase. The specimens used were long compared with their width and thickness thus offering no constraint to lateral contraction. An interpretation of this data in respect of the behaviour of the collagen fibre matrix is postulated.

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