Visualization of microstructural change affected by mechanical stimulation in tendon healing with a novel tensionless model

Microscopy ◽  
2020 ◽  
Author(s):  
Junya Oshima ◽  
Kaoru Sasaki ◽  
Naoto Yamamoto ◽  
Tomoharu Kiyosawa ◽  
Mitsuru Sekido
Keyword(s):  
Mechanical Stimulation ◽  
Three Dimensional ◽  
Tendon Healing ◽  
Dry Weight ◽  
Tendon Sheath ◽  
Tendon Injury ◽  
Collagen Fibers ◽  
Injury Model ◽  
A Cell ◽  
Tendon Tension

Abstract Since the majority of a tendon’s dry weight is collagen fibers, tendon healing consists mainly of collagen repair and observing three-dimensional networks of collagen fibers with scanning electron microscopy (SEM) is optimal for investigating this process. In this report, a cell-maceration/SEM method was used to investigate extrasynovial tendon (unwrapped tendon in synovial tissue such as the tendon sheath) healing of an injured Achilles tendon in a rat model. In addition, since mechanical stimulation is important for tendon healing, a novel, tensionless, rat lower leg tendon injury model was established and verified by visualizing the structural change of collagen fibers under tensionless conditions by SEM. This new model was created by transplanting the leg of a rat with a tendon laceration to the back, removing mechanical stimulation. We then compared the process of tendon healing with and without tension using SEM. Under tension, collagen at the tendon stump shows axial alignment and repair that subsequently demarcates the paratenon (connective tissue on the surface of an extrasynovial tendon) border. In contrast, under tensionless conditions, the collagen remains randomly arranged. Our findings demonstrate that mechanical stimulation contributes to axial arrangement and reinforces the importance of tendon tension in wound healing.

scholarly journals Nonwoven-based gelatin/polycaprolactone membrane loaded with ERK inhibitor U0126 for treatment of tendon defects

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Yonghui Hou ◽  
Bingyu Zhou ◽  
Ming Ni ◽  
Min Wang ◽  
Lingli Ding ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Biomechanical Testing ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Rna Seq ◽  
Injury Model ◽  
New Treatment ◽  
Underlying Mechanisms ◽  
And Control

Abstract Background Tendon is a major component of musculoskeletal system connecting the muscles to the bone. Tendon injuries are very common orthopedics problems leading to impeded motion. Up to now, there still lacks effective treatments for tendon diseases. Methods Tendon stem/progenitor cells (TSPCs) were isolated from the patellar tendons of SD rats. The expression levels of genes were evaluated by quantitative RT-PCR. Immunohistochemistry staining was performed to confirm the presence of tendon markers in tendon tissues. Bioinformatics analysis of data acquired by RNA-seq was used to find out the differentially expressed genes. Rat patellar tendon injury model was used to evaluate the effect of U0126 on tendon injury healing. Biomechanical testing was applied to evaluate the mechanical properties of newly formed tendon tissues. Results In this study, we have shown that ERK inhibitor U0126 rather PD98059 could effectively increase the expression of tendon-related genes and promote the tenogenesis of TSPCs in vitro. To explore the underlying mechanisms, RNA sequencing was performed to identify the molecular difference between U0126-treated and control TSPCs. The result showed that GDF6 was significantly increased by U0126, which is an important factor of the TGFβ superfamily regulating tendon development and tenogenesis. In addition, NBM (nonwoven-based gelatin/polycaprolactone membrane) which mimics the native microenvironment of the tendon tissue was used as an acellular scaffold to carry U0126. The results demonstrated that when NBM was used in combination with U0126, tendon healing was significantly promoted with better histological staining outcomes and mechanical properties. Conclusion Taken together, we have found U0126 promoted tenogenesis in TSPCs through activating GDF6, and NBM loaded with U0126 significantly promoted tendon defect healing, which provides a new treatment for tendon injury.

Therapeutic Mechanisms of Human Adipose-Derived Mesenchymal Stem Cells in a Rat Tendon Injury Model

2017 ◽  
Vol 45 (6) ◽  
pp. 1429-1439 ◽  
Author(s):  
Sang Yoon Lee ◽  
Bomi Kwon ◽  
Kyoungbun Lee ◽  
Young Hoon Son ◽  
Sun G. Chung
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tendon Healing ◽  
Collagen Type I ◽  
Tendon Injury ◽  
Cell Group ◽  
Type I ◽  
Injury Model ◽  
Human Specific

Background: Although survival of transplanted stem cells in vivo and differentiation of stem cells into tenocytes in vitro have been reported, there have been no in vivo studies demonstrating that mesenchymal stem cells (MSCs) could secrete their own proteins as differentiated tenogenic cells. Purpose/Hypothesis: Using a xenogeneic MSC transplantation model, we aimed to investigate whether MSCs could differentiate into the tenogenic lineage and secrete their own proteins. The hypothesis was that human MSCs would differentiate into the human tenogenic lineage and the cells would be able to secrete human-specific proteins in a rat tendon injury model. Study Design: Controlled laboratory study. Methods: The Achilles tendons of 57 Sprague Dawley rats received full-thickness rectangular defects. After the modeling, the defective tendons were randomly assigned to 3 groups: (1) cell group, implantation with human adipose-derived mesenchymal stem cells (hASCs) and fibrin glue (106 cells in 60 μL); (2) fibrin group, implantation with fibrin glue and same volume of cell media; and (3) sham group, identical surgical procedure without any treatment. Gross observation and biomechanical, histopathological, immunohistochemistry, and Western blot analyses were performed at 2 and 4 weeks after modeling. Results: hASCs implanted into the defective rat tendons were viable for 4 weeks as detected by immunofluorescence staining. Tendons treated with hASCs showed better gross morphological and biomechanical recovery than those in the fibrin and sham groups. Furthermore, the expression of both human-specific collagen type I and tenascin-C was significantly higher in the cell group than in the other 2 groups. Conclusion: Transplantation of hASCs enhanced rat tendon healing biomechanically. hASCs implanted into the rat tendon defect model survived for at least 4 weeks and secreted human-specific collagen type I and tenascin-C. These findings suggest that transplanted MSCs may be able to differentiate into the tenogenic lineage and contribute their own proteins to tendon healing. Clinical Relevance: In tendon injury, MSCs can enhance tendon healing by secreting their own protein and have potential as a therapeutic option in human tendinopathy.

The effect of tendon stem/progenitor cell (TSC) sheet on the early tendon healing in a rat Achilles tendon injury model

2016 ◽  
Vol 42 ◽  
pp. 136-146 ◽  
Author(s):  
Issei Komatsu ◽  
James H-C. Wang ◽  
Kiyotaka Iwasaki ◽  
Tatsuya Shimizu ◽  
Teruo Okano
Keyword(s):  
Achilles Tendon ◽  
Progenitor Cell ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Injury Model

scholarly journals CD146 Delineates an Interfascicular Cell Sub-Population in Tendon That Is Recruited during Injury through Its Ligand Laminin-α4

2021 ◽  
Vol 22 (18) ◽  
pp. 9729
Author(s):  
Neil Marr ◽  
Richard Meeson ◽  
Elizabeth F. Kelly ◽  
Yongxiang Fang ◽  
Mandy J. Peffers ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Focal Lesion ◽  
Post Injury ◽  
Surface Receptors ◽  
Basement Membrane Protein ◽  
Injury Model ◽  
Cell Niche

The interfascicular matrix (IFM) binds tendon fascicles and contains a population of morphologically distinct cells. However, the role of IFM-localised cell populations in tendon repair remains to be determined. The basement membrane protein laminin-α4 also localises to the IFM. Laminin-α4 is a ligand for several cell surface receptors, including CD146, a marker of pericyte and progenitor cells. We used a needle injury model in the rat Achilles tendon to test the hypothesis that the IFM is a niche for CD146+ cells that are mobilised in response to tendon damage. We also aimed to establish how expression patterns of circulating non-coding RNAs alter with tendon injury and identify potential RNA-based markers of tendon disease. The results demonstrate the formation of a focal lesion at the injury site, which increased in size and cellularity for up to 21 days post injury. In healthy tendon, CD146+ cells localised to the IFM, compared with injury, where CD146+ cells migrated towards the lesion at days 4 and 7, and populated the lesion 21 days post injury. This was accompanied by increased laminin-α4, suggesting that laminin-α4 facilitates CD146+ cell recruitment at injury sites. We also identified a panel of circulating microRNAs that are dysregulated with tendon injury. We propose that the IFM cell niche mediates the intrinsic response to injury, whereby an injury stimulus induces CD146+ cell migration. Further work is required to fully characterise CD146+ subpopulations within the IFM and establish their precise roles during tendon healing.

scholarly journals Platelet HMGB1 in Platelet-Rich Plasma Promotes Tendon Wound Healing

2021 ◽  
Author(s):  
Jianying Zhang ◽  
Feng Li ◽  
Tyler Augi ◽  
Kelly M. Williamson ◽  
Kentaro Onishi ◽  
...  
Keyword(s):  
Platelet Rich Plasma ◽  
Tendon Healing ◽  
High Mobility ◽  
Tendon Injury ◽  
Tendon Injuries ◽  
Stem Cell Markers ◽  
Wound Area ◽  
Injury Model ◽  
Collagen Iii ◽  
Cell Densities

AbstractPlatelet-rich plasma (PRP) is a widely used autologous treatment for tendon injuries in clinics, but clinical trials often produce conflicting results. Platelets (PLTs) are a major source of high mobility group box1 (HMGB1) that is gaining attention as a chemoattractant that can recruit stem cells to the wound area to enhance healing; however, the contribution of PLT HMGB1 in wounded tendon healing remains unexplored. This study investigated the effect of PLT HMGB1 within PRP to enhance healing in an acute patellar tendon injury model in PLT HMGB1 knockout (KO) mice and GFP mice. A window defect was created in the patellar tendons of both groups of mice, and wounds were treated with either saline, PRP isolated from PLT HMGB1 KO mice, or PRP isolated from GFP mice. Seven days post-treatment, animals were sacrificed and analyzed by gross inspection, histology, and immunostaining for characteristic signs of tendon healing and repair. Our results showed that in comparison to mice treated with PRP from PLT HMGB1-KO mice, wounds treated with PRP from GFP mice healed faster and exhibited a better organization in tendon structure. Mice treated with PRP from PLT HMGB1-KO mice produced tendon tissue with large premature wound areas and low cell densities. However, wounds of PLT HMGB1 KO mice showed better healing with PRP from HMGB1 KO mice compared to saline treatment. Moreover, wounds treated with PRP from GFP mice had increased extracellular HMGB1, decreased CD68, increased stem cell markers CD146 and CD73, and increased collagen III protein expression levels compared to those treated with PRP from PLT HMGB1 KO mice. Thus, PLT HMGB1 within PRP plays an important role in the healing of wounded tendon. Our findings also suggest that the efficacy of PRP treatment for tendon injuries in clinics may be affected by PLT HMGB1 within PRP preparations.

scholarly journals Effectiveness of Ozone Therapy on Tendon Healing: An Experimental Study in Generated Achilles Tendon Injury Model in Rats

2018 ◽  
Vol 27 (4) ◽  
pp. 309-314
Author(s):  
Volkan Kizilkaya ◽  
Vedat Uruc ◽  
Ali Levent ◽  
Ozgur Kanat ◽  
Mustafa Turgut Yildizgoren ◽  
...  
Keyword(s):  
Experimental Study ◽  
Achilles Tendon ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Ozone Therapy ◽  
Injury Model

scholarly journals Comparison of bone surface and trough fixation on bone–tendon healing in a rabbit patella–patellar tendon injury model

2020 ◽  
Vol 21 ◽  
pp. 49-56
Author(s):  
Muzhi Li ◽  
Yifu Tang ◽  
Can Chen ◽  
Jiefu Zhou ◽  
Cheng Zheng ◽  
...  
Keyword(s):  
Patellar Tendon ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Bone Surface ◽  
Injury Model

scholarly journals Image-based Characterization of 3D Collagen Networks and the Effect of Embedded Cells

2019 ◽  
Vol 25 (4) ◽  
pp. 971-981 ◽  
Author(s):  
Vanesa Olivares ◽  
Mar Cóndor ◽  
Cristina Del Amo ◽  
Jesús Asín ◽  
Carlos Borau ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Cell Activity ◽  
Three Dimensional ◽  
Collagen Fibers ◽  
Collagen Gels ◽  
Culture Dish ◽  
Collagen Concentration ◽  
A Cell ◽  
3D Collagen

AbstractCollagen microstructure is closely related to the mechanical properties of tissues and affects cell migration through the extracellular matrix. To study these structures, three-dimensional (3D) in vitro collagen-based gels are often used, attempting to mimic the natural environment of cells. Some key parameters of the microstructure of these gels are fiber orientation, fiber length, or pore size, which define the mechanical properties of the network and therefore condition cell behavior. In the present study, an automated tool to reconstruct 3D collagen networks is used to extract the aforementioned parameters of gels of different collagen concentration and determine how their microstructure is affected by the presence of cells. Two different experiments are presented to test the functionality of the method: first, collagen gels are embedded within a microfluidic device and collagen fibers are imaged by using confocal fluorescence microscopy; second, collagen gels are directly polymerized in a cell culture dish and collagen fibers are imaged by confocal reflection microscopy. Finally, we investigate and compare the collagen microstructure far from and in the vicinities of MDA-MB 23 cells, finding that cell activity during migration was able to strongly modify the orientation of the collagen fibers and the porosity-related values.

scholarly journals Modeling tendon-sheath mechanism with flexible configurations for robot control

Robotica ◽  
2013 ◽  
Vol 31 (7) ◽  
pp. 1131-1142 ◽  
Author(s):  
Zheng Wang ◽  
Zhenglong Sun ◽  
Soo Jay Phee
Keyword(s):  
Three Dimensional ◽  
Tendon Sheath ◽  
Time Varying ◽  
Promising Candidate ◽  
Power Sources ◽  
Tendon Elongation ◽  
Real World Applications ◽  
Tendon Tension ◽  
Fixed Path ◽  
Friction Analysis

SUMMARYSurgical and search/rescue robots often work in environments with very strict spatial constraints. The tendon-sheath mechanism is a promising candidate for driving such systems, allowing power sources and actuation motors placed outside to transmit force and energy to the robot at the distal end through the constrained environment. Having both compactness and high force capability makes it very attractive for manipulation devices. On the other hand, the friction attenuation of tendon tension is nonlinear and configuration-dependent due to tendon/sheath interactions throughout the transmission path. This is a major obstacle for the tendon-sheath mechanism to be widely adopted. Here, we focus on the friction analysis for flexible and time-varying tendon-sheath configurations: the most challenging but yet commonly encountered case for real-world applications. Existing results on fixed-path configurations are reviewed, revisited, and extended to flexible and time-varying cases. The effect of tendon length to friction attenuation is modeled. While focusing on tension transmission, tendon elongation is also discussed with the length effect applied. In the end, two-dimensional results are extended to three-dimensional tendon-sheath configurations. All propositions and theorems are validated on a dedicated experimental platform.

scholarly journals The Symmetric 3D Organization of Connective Tissue around Implant Abutment: A Key-Issue to Prevent Bone Resorption

Symmetry ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1126
Author(s):  
Giovanna Iezzi ◽  
Francesca Di Lillo ◽  
Michele Furlani ◽  
Marco Degidi ◽  
Adriano Piattelli ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Connective Tissue ◽  
Inflammatory Cell ◽  
Soft Tissues ◽  
Three Dimensional ◽  
Collagen Fibers ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Oral Epithelium ◽  
Implant Abutment

Symmetric and well-organized connective tissues around the longitudinal implant axis were hypothesized to decrease early bone resorption by reducing inflammatory cell infiltration. Previous studies that referred to the connective tissue around implant and abutments were based on two-dimensional investigations; however, only advanced three-dimensional characterizations could evidence the organization of connective tissue microarchitecture in the attempt of finding new strategies to reduce inflammatory cell infiltration. We retrieved three implants with a cone morse implant–abutment connection from patients; they were investigated by high-resolution X-ray phase-contrast microtomography, cross-linking the obtained information with histologic results. We observed transverse and longitudinal orientated collagen bundles intertwining with each other. In the longitudinal planes, it was observed that the closer the fiber bundles were to the implant, the more symmetric and regular their course was. The transverse bundles of collagen fibers were observed as semicircular, intersecting in the lamina propria of the mucosa and ending in the oral epithelium. No collagen fibers were found radial to the implant surface. This intertwining three-dimensional pattern seems to favor the stabilization of the soft tissues around the implants, preventing inflammatory cell apical migration and, consequently, preventing bone resorption and implant failure. This fact, according to the authors’ best knowledge, has never been reported in the literature and might be due to the physical forces acting on fibroblasts and on the collagen produced by the fibroblasts themselves, in areas close to the implant and to the symmetric geometry of the implant itself.

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