Journal articles: 'Tendon healing'

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Hope, Matthew, and Terry S. Saxby. "Tendon Healing." Foot and Ankle Clinics 12, no. 4 (December 2007): 553–67. http://dx.doi.org/10.1016/j.fcl.2007.07.003.

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Al-Qattan, Mohammad M., Jeffrey C. Posnick, Kant Y. Lin, and Paul Thorner. "Fetal Tendon Healing." Plastic and Reconstructive Surgery 92, no. 6 (November 1993): 1155–60. http://dx.doi.org/10.1097/00006534-199311000-00024.

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Al-Qattan, Mohammad M., Jeffrey C. Posnick, Kant Y. Lin, Paul Thorner, and John A. I. Grossman. "Fetal Tendon Healing." Plastic and Reconstructive Surgery 92, no. 6 (November 1993): 1161. http://dx.doi.org/10.1097/00006534-199311000-00025.

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MANSKE, P. "Flexor tendon healing." Journal of Hand Surgery: Journal of the British Society for Surgery of the Hand 13, no. 3 (August 1988): 237–45. http://dx.doi.org/10.1016/0266-7681(88)90077-0.

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Manske, Paul R., Richard H. Gelberman, and Peggy A. Lesker. "Flexor Tendon Healing." Hand Clinics 1, no. 1 (February 1985): 25–34. http://dx.doi.org/10.1016/s0749-0712(21)01329-9.

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Chartier, Christian, Hassan ElHawary, Aslan Baradaran, Joshua Vorstenbosch, Liqin Xu, and Johnny Ionut Efanov. "Tendon: Principles of Healing and Repair." Seminars in Plastic Surgery 35, no. 03 (July 15, 2021): 211–15. http://dx.doi.org/10.1055/s-0041-1731632.

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AbstractTendon stores, releases, and dissipates energy to efficiently transmit contractile forces from muscle to bone. Tendon injury is exceedingly common, with the spectrum ranging from chronic tendinopathy to acute tendon rupture. Tendon generally develops according to three main steps: collagen fibrillogenesis, linear growth, and lateral growth. In the setting of injury, it also repairs and regenerates in three overlapping steps (inflammation, proliferation, and remodeling) with tendon-specific durations. Acute injury to the flexor and extensor tendons of the hand are of particular clinical importance to plastic surgeons, with tendon-specific treatment guided by the general principle of minimum protective immobilization followed by hand therapy to overcome potential adhesions. Thorough knowledge of the underlying biomechanical principles of tendon healing is required to provide optimal care to patients presenting with tendon injury.

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Hayashi, M., C. Zhao, K. N. An, and P. C. Amadio. "The effects of growth and differentiation factor 5 on bone marrow stromal cell transplants in an in vitro tendon healing model." Journal of Hand Surgery (European Volume) 36, no. 4 (May 2011): 271–79. http://dx.doi.org/10.1177/1753193410394521.

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The effects of growth differentiation factor-5 (GDF-5) and bone marrow stromal cells (BMSCs) on tendon healing were investigated under in vitro tissue culture conditions. BMSCs and GDF-5 placed in a collagen gel were interpositioned between the cut ends of dog flexor digitorum profundus tendons. The tendons were randomly assigned into four groups: 1) repaired tendon without gel; 2) repaired tendon with BMSC-seeded gel; 3) repaired tendon with GDF-5 gel without cells; and 4) repaired tendon with GDF-5 treated BMSC-seeded gel. At 2 and 4 weeks, the maximal strength of repaired tendons with GDF-5 treated BMSCs-seeded gel was significantly higher than in tendons without gel interposition. However, neither BMSCs nor GDF-5 alone significantly increased the maximal strength of healing tendons at 2 or 4 weeks. These results suggest that the combination of BMSCs and GDF-5 accelerates tendon healing, but either BMSCs or GDF-5 alone are not effective in this model.

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Müller, Sebastian A., Nicholas P. Quirk, Julia A. Müller-Lebschi, Patricia E. Heisterbach, Lutz Dürselen, Martin Majewski, and Christopher H. Evans. "Response of the Injured Tendon to Growth Factors in the Presence or Absence of the Paratenon." American Journal of Sports Medicine 47, no. 2 (December 14, 2018): 462–67. http://dx.doi.org/10.1177/0363546518814534.

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Background: The paratenon is important for Achilles tendon healing. There is much interest in the use of exogenous growth factors (GFs) as potential agents for accelerating the healing of damaged Achilles tendons. Purpose/Hypothesis: The present study used a rat model to study the responses of the injured Achilles tendon to GFs in the presence or absence of the paratenon. The hypothesis was that responses of the injured tendon to GFs would be lower in the absence of a paratenon. Study Design: Controlled laboratory study. Methods: A 4-mm defect was created in the right Achilles tendon of 60 skeletally mature rats, which were treated with a validated combination of GFs (bFGF, BMP-12, and TGF-β1). Animals were randomly assigned to the intact paratenon (IP) group or resected paratenon (RP) group. Healing was studied anatomically, mechanically, and histologically after 1, 2, and 4 weeks. Results: IP tendons showed improved healing compared with RP tendons. IP tendons were significantly stronger (32.2 N and 48.9 N, respectively) than RP tendons (20.1 N and 31.1 N, respectively) after 1 and 2 weeks. IP tendons did not elongate as much as RP tendons and had greater cross-sectional areas (18.0 mm2, 14.4 mm2, and 16.4 mm2, respectively) after 1, 2, and 4 weeks compared with RP tendons (10.5 mm2, 8.4 mm2, and 11.9 mm2, respectively). On histology, earlier collagen deposition and parallel orientation of fibrils were found for IP tendons. Conclusion: The paratenon is essential for efficient Achilles tendon healing. Healing with GFs in this Achilles tendon defect model was superior in the presence of the paratenon. Clinical Relevance: Biological approaches to tendon engineering using GFs are in vogue and have been shown to improve healing of the rat Achilles tendon, most likely by inducing progenitor cells located within the paratenon. Clinically, resection or incision of the paratenon has been proposed for wound closure. Our data demonstrate the fundamental importance of the paratenon, which therefore should be preserved during Achilles tendon repair, especially if augmented with products such as platelet-rich plasma or autologous conditioned serum that are rich in GFs.

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Freedman, Benjamin R., Ashley B. Rodriguez, Cody D. Hillin, Stephanie N. Weiss, Biao Han, Lin Han, and Louis J. Soslowsky. "Tendon healing affects the multiscale mechanical, structural and compositional response of tendon to quasi-static tensile loading." Journal of The Royal Society Interface 15, no. 139 (February 2018): 20170880. http://dx.doi.org/10.1098/rsif.2017.0880.

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Tendon experiences a variety of multiscale changes to its extracellular matrix during mechanical loading at the fascicle, fibre and fibril levels. For example, tensile loading of tendon increases its stiffness, with organization of collagen fibres, and increases cell strain in the direction of loading. Although applied macroscale strains correlate to cell and nuclear strains in uninjured tendon, the multiscale response during tendon healing remains unknown and may affect cell mechanosensing and response. Therefore, this study evaluated multiscale structure–function mechanisms in response to quasi-static tensile loading in uninjured and healing tendons. We found that tendon healing affected the macroscale mechanical and structural response to mechanical loading, evidenced by decreases in strain stiffening and collagen fibre realignment. At the micro- and nanoscales, healing resulted in increased collagen fibre disorganization, nuclear disorganization, decreased change in nuclear aspect ratio with loading, and decreased indentation modulus compared to uninjured tendons. Taken together, this work supports a new concept of nuclear strain transfer attenuation during tendon healing and identifies several multiscale properties that may contribute. Our work also provides benchmarks for the biomechanical microenvironments that tendon cells may experience following cell delivery therapies.

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Yu, Tung-Yang, Jong-Hwei S. Pang, Li-Ping Lin, Ju-Wen Cheng, Shih-Jung Liu, and Wen-Chung Tsai. "Platelet-Rich Plasma Releasate Promotes Early Healing in Tendon After Acute Injury." Orthopaedic Journal of Sports Medicine 9, no. 4 (April 1, 2021): 232596712199037. http://dx.doi.org/10.1177/2325967121990377.

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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.

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He, Min, Aaron Wei Tat Gan, Aymeric Yu Tang Lim, James Cho Hong Goh, James Hoi Po Hui, and Alphonsus Khin Sze Chong. "Bone Marrow Derived Mesenchymal Stem Cell Augmentation of Rabbit Flexor Tendon Healing." Hand Surgery 20, no. 03 (September 21, 2015): 421–29. http://dx.doi.org/10.1142/s0218810415500343.

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Background: This study investigated the effect of mesenchymal stem cell implantation on flexor tendon healing using a rabbit model of flexor tendon repair. Specifically, we compared the difference between autologous and allogeneic stem cells. The influence of cell number on the outcome of flexor tendon healing was also investigated. Methods: Repaired tendons on the rear paws of rabbits were randomly assigned into four groups: control group, 1 million autologous cells, 1 million allogeneic cells, and 4 million allogeneic cells. Rabbits were sacrificed at 3 or 8 weeks after surgery. Results: Implantation of 4 million stem cells resulted in a significant increase in range of motion compared with control group at three weeks after surgery. The positive staining of collagen I in healing tendons was enhanced in stem cell treated groups three weeks after surgery. However, stem cells did not improve biomechanical properties of flexor tendons. Conclusions: High dose stem cells attenuated adhesions in the early time point following flexor tendon repair. Further work is needed determine the value of stem cell therapy in flexor tendon healing in humans.

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Eliasson, Pernilla, Therese Andersson, and Per Aspenberg. "Rat Achilles tendon healing: mechanical loading and gene expression." Journal of Applied Physiology 107, no. 2 (August 2009): 399–407. http://dx.doi.org/10.1152/japplphysiol.91563.2008.

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Injured tendons require mechanical tension for optimal healing, but it is unclear which genes are upregulated and responsible for this effect. We unloaded one Achilles tendon in rats by Botox injections in the calf muscles. The tendon was then transected and left to heal. We studied mechanical properties of the tendon calluses, as well as mRNA expression, and compared them with loaded controls. Tendon calluses were studied 3, 8, 14, and 21 days after transection. Intact tendons were studied similarly for comparison. Altogether 110 rats were used. The genes were chosen for proteins marking inflammation, growth, extracellular matrix, and tendon specificity. In intact tendons, procollagen III and tenascin-C were more expressed in loaded than unloaded tendons, but none of the other genes was affected. In healing tendons, loading status had small effects on the selected genes. However, TNF-α transforming growth factor-β1, and procollagens I and III were less expressed in loaded callus tissue at day 3. At day 8 procollagens I and III, lysyl oxidase, and scleraxis had a lower expression in loaded calluses. However, by days 14 and 21, procollagen I, cartilage oligomeric matrix protein, tenascin-C, tenomodulin, and scleraxis were all more expressed in loaded calluses. In healing tendons, the transverse area was larger in loaded samples, but material properties were unaffected, or even impaired. Thus mechanical loading is important for growth of the callus but not its mechanical quality. The main effect of loading during healing might thereby be sought among growth stimulators. In the late phase of healing, tendon-specific genes (scleraxis and tenomodulin) were upregulated with loading, and the healing tissue might to some extent represent a regenerate rather than a scar.

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Gaughan, E. M., R. M. DeBowes, J. P. Douglass, R. K. Frank, R. D. Klemm, and L. J. Gift. "The Influence of Intratendinous Sodium Hyaluronate on Tendon Healing in Horses." Veterinary and Comparative Orthopaedics and Traumatology 05, no. 04 (1992): 151–57. http://dx.doi.org/10.1055/s-0038-1633108.

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SummaryAcute tendinitis was created bilaterally in the mid-metacarpal region of the deep digital flexor tendons of six horses with intratendinous collagenase administration. The collagenase-induced lesion in one deep digital flexor tendon of each horse was injected 48 h later with 10.0 mg of sodium hyaluronate (1.0 ml) while employing ultrasound guidance. To serve as a control, the lesion in the contralateral deep digital flexor tendon was injected with 1.0 ml of 0.9% sodium chloride. Sequential ultra-sonographic examinations revealed that the sodium hyaluronate treated deep digital flexor tendons were significantly less enlarged and the collagenase-induced tendon lesions significantly smaller than control tendons and tendon lesions. Difference could not be detected between sodium hyaluronate treated tendons and control tendons using histological and video-interactive planar morphometric evaluation six weeks after treatment.Collagenase-induced tendinitis lesions were treated with intratendinous administration of sodium hyaluronate in six horses. The size of the tendon lesions and the amount of tendon enlargement were significantly less in the sodium hyaluronate treated tendons compared to control tendons. A significant difference in the rate or quality of healing was not detected in the sodium hyaluronate treated tendons.

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Gargano, Giuseppe, Antonio Oliviero, Francesco Oliva, and Nicola Maffulli. "Small interfering RNAs in tendon homeostasis." British Medical Bulletin 138, no. 1 (January 18, 2021): 58–67. http://dx.doi.org/10.1093/bmb/ldaa040.

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Abstract Background Tenogenesis and tendon homeostasis are guided by genes encoding for the structural molecules of tendon fibres. Small interfering RNAs (siRNAs), acting on gene regulation, can therefore participate in the process of tendon healing. Sources of data A systematic search of different databases to October 2020 identified 17 suitable studies. Areas of agreement SiRNAs can be useful to study reparative processes of tendons and identify possible therapeutic targets in tendon healing. Areas of controversy Many genes and growth factors involved in the processes of tendinopathy and tendon healing can be regulated by siRNAs. It is however unclear which gene silencing determines the expected effect. Growing points Gene dysregulation of growth factors and tendon structural proteins can be influenced by siRNA. Areas timely for developing research It is not clear whether there is a direct action of the siRNAs that can be used to facilitate the repair processes of tendons.

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Rodeo, Scott A., and Kazutaka Izawa. "Tendon-to-Bone Healing." Techniques in Orthopaedics 14, no. 1 (March 1999): 22–33. http://dx.doi.org/10.1097/00013611-199903000-00004.

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Holey, Liz. "Tendon and Ligament Healing." Physiotherapy 86, no. 6 (June 2000): 326. http://dx.doi.org/10.1016/s0031-9406(05)61010-3.

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Kiss, ZS, DP Kellaway, JI Cook, and et al. "Postoperative patellar tendon healing." Clinical Imaging 22, no. 5 (September 1998): 378–79. http://dx.doi.org/10.1016/s0899-7071(98)00046-1.

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Platt, Marc A. "Tendon Repair and Healing." Clinics in Podiatric Medicine and Surgery 22, no. 4 (October 2005): 553–60. http://dx.doi.org/10.1016/j.cpm.2005.08.001.

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Galvez, M. G., C. Crowe, S. Farnebo, and J. Chang. "Tissue engineering in flexor tendon surgery: current state and future advances." Journal of Hand Surgery (European Volume) 39, no. 1 (November 21, 2013): 71–78. http://dx.doi.org/10.1177/1753193413512432.

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Tissue engineering of flexor tendons addresses a challenge often faced by hand surgeons: the restoration of function and improvement of healing with a limited supply of donor tendons. Creating an engineered tendon construct is dependent upon understanding the normal healing mechanisms of the tendon and tendon sheath. The production of a tendon construct includes: creating a three-dimensional scaffold; seeding cells within the scaffold; encouraging cellular growth within the scaffold while maintaining a gliding surface; and finally ensuring mechanical strength. An effective construct incorporates these factors in its design, with the ultimate goal of creating tendon substitutes that are readily available to the reconstructive hand surgeon.

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Zhang, Kairui, Michael W. Hast, Soutarou Izumi, Yu Usami, Snehal Shetye, Ngozi Akabudike, Nancy J. Philp, et al. "Modulating Glucose Metabolism and Lactate Synthesis in Injured Mouse Tendons: Treatment With Dichloroacetate, a Lactate Synthesis Inhibitor, Improves Tendon Healing." American Journal of Sports Medicine 46, no. 9 (June 21, 2018): 2222–31. http://dx.doi.org/10.1177/0363546518778789.

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Background: Tendon injuries are common problems among athletes. Complete recovery of the mechanical structure and function of ruptured tendons is challenging. It has been demonstrated that upregulation of glycolysis and lactate production occurs in wounds, inflammation sites, and cancerous tumors, and these metabolic changes also control growth and differentiation of stem and progenitor cells. Similar metabolic changes have been reported in human healing tendons. In addition, lactate production has increased in progenitors isolated from injured tendons after treatment with IL-1β. It is thought that the metabolic changes play a role in tendon healing after injury. Hypothesis: Glucose metabolism is altered during tendon injury and healing, and modulation of this altered metabolism improves tendon repair. Study Design: Controlled laboratory study. Methods: The authors used the tendon injury model involving a complete incision of the Achilles tendon in C57BL/6J female mice and studied alterations of glucose metabolism in injured tendons with [U-13C]glucose and metabolomics analysis 1 and 4 weeks after surgery. They also examined the effects of dichloroacetate (DCA; an indirect lactate synthesis inhibitor) treatment on the recovery of structure and mechanical properties of injured tendons 4 weeks after surgery in the same mouse model. Results: Significant changes in glucose metabolism in tendons after injury surgery were detected. 13C enrichment of metabolites and intermediates, flux through glycolysis, and lactate synthesis, as well as tricarboxylic acid cycle activity, were acutely increased 1 week after injury. Increased glycolysis and lactate generation were also found 4 weeks after injury. DCA-treated injured tendons showed decreased cross-sectional area and higher values of modulus, maximum stress, and maximum force when compared with vehicle-treated injured tendons. Improved alignment of the collagen fibers was also observed in the DCA group. Furthermore, DCA treatment reduced mucoid accumulation and ectopic calcification in injured tendons. Conclusion: The findings indicate that injured tendons acutely increase glycolysis and lactate synthesis after injury and that the inhibition of lactate synthesis by DCA is beneficial for tendon healing. Clinical Relevance: Changing metabolism in injured tendons may be a therapeutic target for tendon repair.

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NESSLER, J. P., P. C. AMADIO, L. J. BERGLUND, and K. N. AN. "Healing of Canine Tendon in Zones Subjected to Different Mechanical Forces." Journal of Hand Surgery 17, no. 5 (October 1992): 561–68. http://dx.doi.org/10.1016/s0266-7681(05)80242-6.

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The effect of external force environment on the healing of a partial thickness injury to canine flexor tendon was studied. A 50% laceration was made in either the fibrocartilaginous (compressive) zone or in the tendinous (tensile) zone of canine flexor digitorum profundus tendons. After three or six weeks, the tendons were harvested. An optical method for determining zone-specific material properties showed that, in response to injury, the structural stiffness decreased in the tensile zone of the tendon but increased in the compressive zone. The mechanical properties and failure mechanism of canine tendon and their changes in response to injury vary according to tendon zone, and differences in the healing process in mechanically specialised zones of the flexor tendon are discussed.

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Costa-Almeida, Raquel, Isabel Calejo, and Manuela E. Gomes. "Mesenchymal Stem Cells Empowering Tendon Regenerative Therapies." International Journal of Molecular Sciences 20, no. 12 (June 19, 2019): 3002. http://dx.doi.org/10.3390/ijms20123002.

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Tendon tissues have limited healing capacity. The incidence of tendon injuries and the unsatisfactory functional outcomes of tendon repair are driving the search for alternative therapeutic approaches envisioning tendon regeneration. Cellular therapies aim at delivering adequate, regeneration-competent cell types to the injured tendon and toward ultimately promoting its reconstruction and recovery of functionality. Mesenchymal stem cells (MSCs) either obtained from tendons or from non-tendon sources, like bone marrow (BM-MSCs) or adipose tissue (ASCs), have been receiving increasing attention over the years toward enhancing tendon healing. Evidences from in vitro and in vivo studies suggest MSCs can contribute to accelerate and improve the quality of tendon healing. Nonetheless, the exact mechanisms underlying these repair events are yet to be fully elucidated. This review provides an overview of the main challenges in the field of cell-based regenerative therapies, discussing the role of MSCs in boosting tendon regeneration, particularly through their capacity to enhance the tenogenic properties of tendon resident cells.

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Noah, Andrew C., Thomas M. Li, Leandro M. Martinez, Susumu Wada, Jacob B. Swanson, Nathaniel P. Disser, Kristoffer B. Sugg, Scott A. Rodeo, Theresa T. Lu, and Christopher L. Mendias. "Adaptive and innate immune cell responses in tendons and lymph nodes after tendon injury and repair." Journal of Applied Physiology 128, no. 3 (March 1, 2020): 473–82. http://dx.doi.org/10.1152/japplphysiol.00682.2019.

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Tendon injuries are a common clinical condition with limited treatment options. The cellular components of the innate immune system, such as neutrophils and macrophages, have been studied in tendon injuries. However, the adaptive immune system, comprising specialized lymphocytes, plays an important role in orchestrating the healing of numerous tissues, but less is known about these cells in tendon healing. To gain a greater understanding of the biological processes that regulate tendon healing, we determined how the cellular components of the adaptive and innate immune system respond to a tendon injury using two-month-old male mice. We observed that lymphatic vasculature is present in the epitenon and superficial regions of Achilles tendons, and that the lymphatics drain into the popliteal lymph node. We then created an acute Achilles tenotomy followed by repair, and collected tendons and popliteal lymph nodes 1, 2, and 4 wk after injury. Tendon injury resulted in a robust adaptive immune cell response that followed an initial innate immune cell response in tendons and lymph nodes. Monocytes, neutrophils, and macrophages initially accumulated at 1 wk after injury in tendons, while dendritic cells and CD4+ T cells peaked at 2 wk after injury. B cells and CD8+ T cells progressively increased over time. In parallel, immune cells of the popliteal lymph node demonstrated a similarly coordinated response to the injury. These results suggest that there is an adaptive immune response to tendon injury, and adaptive immune cells may play a role in regulating tendon healing. NEW & NOTEWORTHY While the innate immune system, consisting of macrophages and related hematopoietic cells, has been studied in tendon injury, less is known about the adaptive immune system. Using a mouse model of Achilles tendon tenotomy and repair, we observed an adaptive immune cell response, consisting of CD4+ and CD8+ T cells, and B cells, which occur through 4 wk after tendon injury. This response appeared to be coordinated by the draining popliteal lymph node.

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Müller, Sebastian A., Christopher H. Evans, Patricia E. Heisterbach, and Martin Majewski. "The Role of the Paratenon in Achilles Tendon Healing: A Study in Rats." American Journal of Sports Medicine 46, no. 5 (March 5, 2018): 1214–19. http://dx.doi.org/10.1177/0363546518756093.

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Background: The role of the paratenon in tendon healing is unknown. The present study compares healing in the presence or absence of the paratenon in an Achilles tendon defect model in rats. Hypothesis: Resection of the paratenon impairs tendon healing. Study Design: Controlled laboratory study. Methods: Sixty skeletally mature Sprague Dawley rats were randomly assigned to either a resected paratenon (RP) group or an intact paratenon (IP) group. In all animals, a 4-mm portion of the Achilles tendon was resected in the midsubstance. In the RP group, the paratenon was resected completely. In the IP group, the paratenon was opened longitudinally and closed again after the tendon defect had been created. One, 2, and 4 weeks after surgery, 7 animals per group were tested biomechanically and 3 animals per group examined histologically. Results: The recovery of mechanical strength was much more rapid in IP tendons. Tear resistance was significantly increased for IP tendons (41.3 ± 8.8 N and 47.3 ± 14.1 N, respectively) compared with RP tendons (19.3 ± 9.1 N and 33.2 ± 6.4 N, respectively) after 1 and 2 weeks. The cross-sectional area was larger in the IP group after 1 and 2 weeks (8.2 ± 2.3 mm2 and 11.3 ± 3.1 mm2 vs 5.0 ± 2.4 mm2 and 5.9 ± 2.0 mm2, respectively) compared with the RP group. Tendon stiffness was greater in the IP group after 1 week (10.4 ± 1.9 N/mm vs 4.5 ± 1.6 N/mm, respectively) compared with the RP group. In comparison, normal contralateral tendons had a maximal tear resistance of 56.6 ± 7.2 N, a cross-sectional area of 3.6 ± 0.7 mm2, and stiffness of 17.3 ± 3.8 N/mm. Hematoxylin and eosin staining revealed slightly delayed healing of RP tendons. Early collagen formation was seen in the IP group already after 1 week, whereas in the RP group, this only occurred after 2 weeks. After 4 weeks, the IP tendons showed more collagen crimp formation than the RP tendons. Conclusion: An intact paratenon promotes healing of the Achilles tendon. Clinical Relevance: Although incision or resection of the paratenon has been advocated when repairing injured or degenerative tendons, our data suggest that the integrity of the paratenon should be preserved.

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AL-QATTAN, M. M., J. C. POSNICK, and K. Y. LIN. "The In Vivo Response of Foetal Tendons to Sutures." Journal of Hand Surgery 20, no. 3 (June 1995): 314–18. http://dx.doi.org/10.1016/s0266-7681(05)80085-3.

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The in vivo response of foetal flexor digitorum profundus tendons to tendon sutures was studied macroscopically and microscopically in foetal lambs. No tendon adhesions were noted at any of the examination intervals. 4 days after injury, a mild inflammatory reaction was noted around the suture. The tendon examined at the 4-week interval showed evidence of migration of epitenon cells from the outer surface of the tendon into the suture track. The tendon examined at the 6-week interval showed normal tendon fibres surrounding the suture site. Differences between foetal skin and foetal tendon healing are discussed along with the possible role of amniotic fluid in modulating the healing process in the foetus.

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Gift, L. J., R. M. De Bowes, R. Basaraba, J. Roush, and E. M. Gaughan. "The Influence of Sequential Intratendinous Sodium Hyaluronate on Tendon Healing in Horses." Veterinary and Comparative Orthopaedics and Traumatology 08, no. 01 (1995): 40–45. http://dx.doi.org/10.1055/s-0038-1632425.

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SummaryAcute tendinitis was bilaterally created in the mid-metacarpal region of the superficial digital flexor tendons of six horses with intratendinous collagenase administration. The collagenase-induced lesion, in one superficial flexor tendon of each horse, was injected 48 h later with 10.0 mg of sodium hyaluronate (1.0 ml) under ultrasound guidance. In order to serve as a control, the lesion in the contralateral superficial digital flexor tendon was injected with 1.0 ml of phosphate buffered 0.9% sodium chloride. Similar injections were made at weekly intervals for six weeks. Differences could not be detected between sequential sodium hyaluronate treated tendons and control tendons using ultrasonographic, lameness, gross pathological nor histological evaluations.Collagenase-induced superficial digital flexor tendinitis lesions were treated with repeated, sequential intratendinous administration of sodium hyaluronate in six horses. A significant difference in size of the tendon lesions, tendon enlargement, lameness, or tendon healing was not detected between repeated, sequential intratendinous sodium hyaluronate treated and control tendons. The multiple intratendinous injection is not recommended for horses with flexor tendinitis.

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Andersson, Therese, Pernilla Eliasson, Malin Hammerman, Olof Sandberg, and Per Aspenberg. "Low-level mechanical stimulation is sufficient to improve tendon healing in rats." Journal of Applied Physiology 113, no. 9 (November 1, 2012): 1398–402. http://dx.doi.org/10.1152/japplphysiol.00491.2012.

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Treatment of tendon injuries often involves immobilization. However, immobilization might not prevent mild involuntary isometric muscle contraction. The effect of weak forces on tendon healing is therefore of clinical interest. Studies of tendon healing with various methods for load reduction in rat Achilles tendon models show a consistent reduction in tendon strength by at least half, compared with voluntary cage activity. Unloading was not complete in any of these models, and the healing tendon was therefore still exposed to mild mechanical stimulation. By reducing the forces acting on the tendon even further, we now studied the effects of this mild stimulation. Rat Achilles tendons were transected and allowed to heal spontaneously under four different loading conditions: 1) normal cage activity; 2) calf muscle paralysis induced by botulinum toxin A (Botox); 3) tail suspension; 4) Botox and tail suspension, combined, to eliminate even mild stimulation. Healing was evaluated by mechanical testing after 8 days. Botox alone and suspension alone both reduced tendon callus size (transverse area), thereby impairing its strength compared with normal cage activity. The combination of Botox and suspension did not further reduce tendon callus size but drastically impaired the material properties of the tendon callus compared with each treatment alone. The peak force was only a fifth of that in the normal cage activity group. The results indicate that also the mild loading that occurs with either Botox or suspension alone stimulates tendon healing. This stimulation appears to affect mainly tissue quality, whereas stronger stimulation also increases callus size.

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Singh, Rohit, Jihad Alzyoud, Ryan Trickett, Peter Thomas, Peter Theobald, and Ilyas Khan. "Growth Factor and Intense Pulse Light in Flexor Tendon Repair: A Biomechanical Study at Strength and Gap Resistance." Journal of Hand Surgery (Asian-Pacific Volume) 23, no. 04 (November 15, 2018): 463–68. http://dx.doi.org/10.1142/s2424835518500431.

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Background: Flexor tendon injuries are extremely common and they are usually the result of incised traumatic glass or knife injury. The process of tendon healing is a complicated and exceptionally-regimented mechanism that is originated and monitored by a vast number of diverse molecules. One of the most pivotal groups of mediators that are crucial to the healing process are growth factors (GF). Intense pulse light (IPL) can lead to evidence of new collagen formation with associated clinical improvement in tissue healing. The biological benefit of Intense pulse light (IPL) relies on judicious photothermolysis, where heat driven radiation is dissipated and focused at the cellular level. The aims of this study is to set out the effect of growth factor and IPL on healing following a tendon repair. Methods: Bovine common digital extensor tendons (CDET) were used as an ex vivo model. 44 tendon repairs were performed by the lead author using 2.5 × magnification loupes and standard instruments. Clamped tendons were assigned into the following groups; control, IPL, GF, IPL and GF. After culturing, biomechanical testing was carried out using monotonic tensile testing with displacement-controlled uniaxial tension to failure. Results: The mean values for ultimate tensile stress (UTS) for the control group was 53.51 N, for IPL it was 51.15 N, for growth factor was 70.10 N and for combined growth factor and IPL it was 75.16 N. Conclusions: This study showed significant improvement in UTS when repaired tendons were cultured with growth factor compared to control and IPL. This would suggest a biomechanical advantage for tendon healing.

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Tzoanos, Georgios Nikolaos, Nikolaos Tsavalas, Nikolaos Manidakis, and Alkiviadis Kalliakmanis. "Patellar tendon healing after anterior cruciate ligament reconstruction in football players." Orthopaedic Journal of Sports Medicine 5, no. 2_suppl2 (February 1, 2017): 2325967117S0004. http://dx.doi.org/10.1177/2325967117s00043.

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Introduction: To investigate the healing process of the harvested patellar tendon at 12±2 and 24±2 months following Bone-Patellar-Bone (BTB) Anterior Cruciate Ligament (ACL) reconstruction. Methods: 30 football players were enrolled in our study and examined at 12±2 and 24±2 months postoperatively. Donor and contralateral tendons evaluated with a high frequency ultrasound transducer. The maximum anteroposterior (MAP) and maximum transverse (MT) diameters of the patellar tendon and associated defect at the site of the tendon incision measured at its proximal, middle and distal thirds. The presence of vascular flow was examined with Doppler imaging. Echogenicity of the patellar tendon defect was graded as low, mixed or normal compared to the contralateral tendon. Results: There was no statistically significant difference between the mean MAP and MT diameters of the donor tendons at 12±2 and 24±2 months postoperatively (P>0.05). The mean MAP and MT diameters of the patellar tendon defect at 24±2 months were significantly smaller compared to 12±2 months postoperatively (P<0.01). The mean MAP diameter of the harvested tendon was significantly greater at all measured sites in comparison to the contralateral tendon at 12±2 and 24±2 months postoperatively (P<0.01). There was no statistically significant difference between the mean MT diameters of the donor and healthy tendons at 12±2 and 24±2 months postoperatively (P>0.05). At 12±2 months, the mean MAP diameter of the patellar tendon defect was 4.0±2.1 mm, 4.7±2.8 mm and 4.1±2.4 mm at the proximal, middle and distal third of the tendon respectively. The mean MT diameter of the defect was 3.3±2.2 mm (proximal third), 2.9±1.6 mm (middle third) and 2.1±0.9 mm (distal third). 2 of tendon defects showed low echogenicity, 6 mixed echogenicity, 2 patients normal echogenicity. At 24±2 months the mean MAP diameter of the patellar tendon defect was 0.3±0.3 mm, 0.4±0.4 mm and 0.3±0.3 mm at the proximal, middle and distal third of the tendon respectively. The mean MT diameter of the defect was 0.3±0.3 mm (proximal third), 0.2±0.2 mm (middle third) and 0.2±0.2 mm (distal third). 27 of patients demonstrated normal echogenicity, 1 low echogenicity, while 2 mixed echogenicity. No tendon exhibited any signs of neovascularization at 12±2 and 24±2 months postoperatively. Conclusions: Patellar tendons after BTB ACL reconstruction were characterized by increased thickness at 12±2 and 24±2 months postoperatively. Solid healing were evident in 2 patients by 12±2 months and in 27 by 24±2 months. No inflammatory changes were observed at 12±2 and 24±2 months postoperatively. [Figure: see text][Figure: see text]

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Liu, Hsin-Yi, Troy Blackburn, Darin Padua, R. Alexander Creighton, and Paul Weinhold. "In vivoUltrasonographic Evaluation of Patellar Tendon Stiffness after Anterior Cruciate Ligament Reconstruction with Patellar Tendon Autograft." Applied Bionics and Biomechanics 8, no. 3-4 (2011): 367–76. http://dx.doi.org/10.1155/2011/438747.

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Background:Tendon mechanical properties have been used to evaluate the effects of therapies on the healing of animal tendons, but these measures have not been convenient to record in vivo in humans due to their invasive nature. The aims of this study were to assess the capability of an ultrasonography technique to track the change in stiffness of the healing human patellar tendon and to assess the correlation between stiffness parameters and clinical recovery measurements.Method:Ten subjects undergoing anterior cruciate ligament reconstruction with a patellar tendon autograft were recruited for the study as well as 10 healthy control subjects. The surgical tendons' mechanical properties were evaluated at 2 and 6 months after surgery with a two-scan ultrasonography technique. A paired sign-rank test was performed to compare the change in biomechanical parameters and clinical recovery measurements across time between surgical and control groups.Results:Tendon stiffness of the surgical group increased from ~71% to ~94% when compared to the stiffness of the contralateral tendons at the first visit; however, the difference was not significant (P= 0.18). Significant improvements were shown in all the clinical recovery outcomes. Poor correlation was found between the clinical recovery measurements and tendon stiffness.Conclusions:No significant change in patellar tendon stiffness with healing was detected over the 2–6 month period after surgery, suggesting the tendon stiffness recovery in humans proceeds more slowly than other clinical measures.

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Andersson, Therese, Pernilla Eliasson, and Per Aspenberg. "Tissue memory in healing tendons: short loading episodes stimulate healing." Journal of Applied Physiology 107, no. 2 (August 2009): 417–21. http://dx.doi.org/10.1152/japplphysiol.00414.2009.

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Intact tendons adapt slowly to changes in mechanical loading, whereas in healing tendons the effect of mechanical loading or its absence is dramatic. The longevity of the response to a single loading episode is, however, unknown. We hypothesized that the tissue has a “memory” of loading episodes and that therefore short loadings are sufficient to elicit improved healing. The Achilles tendon of 70 female rats was transected and unloaded by tail suspension for 12 days (suspension started on day 2 after surgery). Each day, the rats were let down from suspension for short daily training episodes according to different regimes: 15 min of cage activity or treadmill running for 15, 30, 60, or 2 × 15 min. Rats with transected Achilles tendons and full-time cage activity served as controls. The results demonstrated that full-time cage activity increased the peak force over three times compared with unloading. Short daily loading episodes (treadmill running) increased the peak force about half as much as full-time activity. Prolongation of treadmill running above 15 min or dividing the daily training in two separate episodes had minimal further effect. This mechanical stimulation increased the cross-sectional area but had no effect on the mechanical properties of the repair tissue. The findings indicate that once the tissue had received information from a certain loading type and level, this is “memorized” and leads to a response lasting many hours. This suggests that patients might be allowed early short loading episodes following, e.g., an Achilles tendon rupture for a better outcome.

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Ackermann, Paul, W. "Neuronal pathways in tendon healing." Frontiers in Bioscience 14, no. 1 (2009): 5165. http://dx.doi.org/10.2741/3593.

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Fox, Alice J. S., and George A. C. Murrell. "Nitric Oxide and Tendon Healing." Techniques in Orthopaedics 22, no. 1 (March 2007): 14–19. http://dx.doi.org/10.1097/01.bto.0000261739.62283.1e.

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Oliva, Francesco, Stefano Gatti, Giuseppe Porcellini, Nicholas R. Forsyth, and Nicola Maffulli. "Growth factors and tendon healing." Scottish Medical Journal 55, no. 2 (May 2010): 35. http://dx.doi.org/10.1258/rsmsmj.55.2.35d.

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Voleti, Pramod B., Mark R. Buckley, and Louis J. Soslowsky. "Tendon Healing: Repair and Regeneration." Annual Review of Biomedical Engineering 14, no. 1 (August 15, 2012): 47–71. http://dx.doi.org/10.1146/annurev-bioeng-071811-150122.

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Möller, H. D., C. H. Evans, and N. Maffulli. "New strategies for tendon healing." Der Orthopäde 29, no. 3 (March 24, 2000): 0182–87. http://dx.doi.org/10.1007/s001320050436.

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Hiramatsu, Kunihiko, Akira Tsujii, Norimasa Nakamura, and Tomoki Mitsuoka. "Ultrasonographic Evaluation of the Early Healing Process After Achilles Tendon Repair." Orthopaedic Journal of Sports Medicine 6, no. 8 (August 1, 2018): 232596711878988. http://dx.doi.org/10.1177/2325967118789883.

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Background: Little is known about early healing of repaired Achilles tendons on imaging, particularly up to 6 months postoperatively, when patients generally return to participation in sports. Purpose: To examine changes in repaired Achilles tendon healing with ultrasonography for up to 12 months after surgery. Study Design: Case series; Level of evidence, 4. Methods: Ultrasonographic images of 26 ruptured Achilles tendons were analyzed at 1, 2, 3, 4, 6, and 12 months after primary repair. The cross-sectional areas (CSAs) and intratendinous morphology of the repaired tendons were evaluated using the authors’ own grading system (tendon repair scores), which assessed the anechoic tendon defect area, intratendinous hyperechoic area, continuity of intratendinous fibrillar appearance, and paratendinous edema. Results: The mean ratios (%) of the CSA for the affected versus unaffected side of repaired Achilles tendons gradually increased postoperatively, reached a maximum (632%) at 6 months, and then decreased at 12 months. The mean tendon repair scores increased over time and reached a plateau at 6 months. Conclusion: Ultrasonography is useful to observe the intratendinous morphology of repaired Achilles tendons and to provide useful information for patients who wish to return to sports. Clinical parameters such as strength, functional performance, and quality of healed repaired tendons should also be assessed before allowing patients to return to sports.

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Zenchenko, A. V., and Yu M. Cherniakova. "COMPARISON OF 3-WEEK CALCANEAL TENDON REGENERATES AFTER TENOTOMY AND SUTURING IN EXPERIMENT IN VIVO." Journal of the Grodno State Medical University 19, no. 1 (February 25, 2021): 77–84. http://dx.doi.org/10.25298/2221-8785-2021-19-1-77-84.

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Background. Modern knowledge about tendon healing as well as possibilities of hand surgery does not solve the problem of tenogenic contractures. For the prevention of cicatricial process, the separation of the sliding surfaces of the tendon and its sheath with polymeric materials is used. However, regeneration of tendons in condition of isolation has not been proven. Aim of the research. In a laboratory animal model to perform a tenotomy and a calcaneal tendon suture, study 3-week regenerates formed in the mobilization regime and evaluate the regenerative capacity of the tendon isolated with a dissected polymer tube. Material and methods. On both paws of laboratory rats tenotomy and suturing of the calcaneal tendons were performed. The tendons on the right paws were isolated with dissected polymeric tubes. The appearance and the histological structure of the suture site were assessed after 3 weeks. Results. Tendon regenerates were distinguished by their maturity and tissue organization. Tendons without isolation healed faster, but lost their sliding surface. As a result of isolation, a sliding surface of the tendon and its sheath was formed, but the formation of the regenerate slowed down. Conclusions. Tendon healing in dissected tube is possible and occurs due to intrinsic repair. The fusion of the tendon demonstrates a well-vascularized regenerate in the suture site.

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Eliasson, Pernilla, Therese Andersson, and Per Aspenberg. "Influence of a single loading episode on gene expression in healing rat Achilles tendons." Journal of Applied Physiology 112, no. 2 (January 2012): 279–88. http://dx.doi.org/10.1152/japplphysiol.00858.2011.

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Mechanical loading stimulates tendon healing via mechanisms that are largely unknown. Genes will be differently regulated in loaded healing tendons, compared with unloaded, just because of the fact that healing processes have been changed. To avoid such secondary effects and study the effect of loading per se, we therefore studied the gene expression response shortly after a single loading episode in otherwise unloaded healing tendons. The Achilles tendon was transected in 30 tail-suspended rats. The animals were let down from the suspension to load their tendons on a treadmill for 30 min once, 5 days after tendon transection. Gene expression was studied by Affymetrix microarray before and 3, 12, 24, and 48 h after loading. The strongest response in gene expression was seen 3 h after loading, when 150 genes were up- or downregulated (fold change ≥2, P ≤ 0.05). Twelve hours after loading, only three genes were upregulated, whereas 38 were downregulated. Fewer than seven genes were regulated after 24 and 48 h. Genes involved in the inflammatory response were strongly regulated at 3 and 12 h after loading; this included upregulation of iNOS, PGE synthase, and IL-1β. Also genes involved in wound healing/coagulation, angiogenesis, and production of reactive oxygen species were strongly regulated by loading. Microarray results were confirmed for 16 selected genes in a repeat experiment ( N = 30 rats) using real-time PCR. It was also confirmed that a single loading episode on day 5 increased the strength of the healing tendon on day 12. In conclusion, the fact that there were hardly any regulated genes 24 h after loading suggests that optimal stimulation of healing requires a mechanical loading stimulus every day.

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Inoue, Hiroshi, Kotaro Imamura, Yoshifumi Nagatani, Toru Hirano, and Katsurou Iwasaki. "Experimental study of Tendon Healing. Histological Study of Tendon Healing in Rabbit Knee Joints." Orthopedics & Traumatology 40, no. 1 (1991): 410–13. http://dx.doi.org/10.5035/nishiseisai.40.410.

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McCarron, Jesse A., Kathleen A. Derwin, Michael J. Bey, Joshua M. Polster, Jean P. Schils, Eric T. Ricchetti, and Joseph P. Iannotti. "Failure With Continuity in Rotator Cuff Repair “Healing”." American Journal of Sports Medicine 41, no. 1 (September 27, 2012): 134–41. http://dx.doi.org/10.1177/0363546512459477.

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Background: Ten to seventy percent of rotator cuff repairs form a recurrent defect after surgery. The relationship between retraction of the repaired tendon and formation of a recurrent defect is not well defined. Purpose/Hypotheses: To measure the prevalence, timing, and magnitude of tendon retraction after rotator cuff repair and correlate these outcomes with formation of a full-thickness recurrent tendon defect on magnetic resonance imaging, as well as clinical outcomes. We hypothesized that (1) tendon retraction is a common phenomenon, although not always associated with a recurrent defect; (2) formation of a recurrent tendon defect correlates with the timing of tendon retraction; and (3) clinical outcome correlates with the magnitude of tendon retraction at 52 weeks and the formation of a recurrent tendon defect. Study Design: Case series; Level of evidence, 4. Methods: Fourteen patients underwent arthroscopic rotator cuff repair. Tantalum markers placed within the repaired tendons were used to assess tendon retraction by computed tomography scan at 6, 12, 26, and 52 weeks after operation. Magnetic resonance imaging was performed to assess for recurrent tendon defects. Shoulder function was evaluated using the Penn score, visual analog scale (VAS) score for pain, and isometric scapular-plane abduction strength. Results: All rotator cuff repairs retracted away from their position of initial fixation during the first year after surgery (mean [standard deviation], 16.1 [5.3] mm; range, 5.7-23.2 mm), yet only 30% of patients formed a recurrent defect. Patients who formed a recurrent defect tended to have more tendon retraction during the first 6 weeks after surgery (9.7 [6.0] mm) than those who did not form a defect (4.1 [2.2] mm) ( P = .08), but the total magnitude of tendon retraction was not significantly different between patient groups at 52 weeks. There was no significant correlation between the magnitude of tendon retraction and the Penn score ( r = 0.01, P = .97) or normalized scapular abduction strength ( r = −0.21, P = .58). However, patients who formed a recurrent defect tended to have lower Penn scores at 52 weeks ( P = .1). Conclusion: Early tendon retraction, but not the total magnitude, correlates with formation of a recurrent tendon defect and worse clinical outcomes. “Failure with continuity” (tendon retraction without a recurrent defect) appears to be a common phenomenon after rotator cuff repair. These data suggest that repairs should be protected in the early postoperative period and repair strategies should endeavor to mechanically and biologically augment the repair during this critical early period.

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Ingraham, John M., Randy M. Hauck, and H. Paul Ehrlich. "Is the Tendon Embryogenesis Process Resurrected during Tendon Healing?" Plastic and Reconstructive Surgery 112, no. 3 (September 2003): 844–54. http://dx.doi.org/10.1097/01.prs.0000070180.62037.fc.

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Wu, Ya Fang, and Jin Bo Tang. "Tendon Healing, Edema, and Resistance to Flexor Tendon Gliding." Hand Clinics 29, no. 2 (May 2013): 167–78. http://dx.doi.org/10.1016/j.hcl.2013.02.002.

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Fryhofer, George W., Benjamin R. Freedman, Cody D. Hillin, Nabeel S. Salka, Adam M. Pardes, Stephanie N. Weiss, Daniel C. Farber, and Louis J. Soslowsky. "Postinjury biomechanics of Achilles tendon vary by sex and hormone status." Journal of Applied Physiology 121, no. 5 (November 1, 2016): 1106–14. http://dx.doi.org/10.1152/japplphysiol.00620.2016.

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Achilles tendon ruptures are common injuries. Sex differences are present in mechanical properties of uninjured Achilles tendon, but it remains unknown if these differences extend to tendon healing. We hypothesized that ovariectomized females (OVX) and males would exhibit inferior postinjury tendon properties compared with females. Male, female, and OVX Sprague-Dawley rats ( n = 32/group) underwent acclimation and treadmill training before blunt transection of the Achilles tendon midsubstance. Injured hindlimbs were immobilized for 1 wk, followed by gradual return to activity and assessment of active and passive hindlimb function. Animals were euthanized at 3 or 6 wk postinjury to assess tendon structure, mechanics, and composition. Passive ankle stiffness and range of motion were superior in females at 3 wk; however, by 6 wk, passive and active function were similar in males and females but remained inferior in OVX. At 6 wk, female tendons had greater normalized secant modulus, viscoelastic behavior, and laxity compared with males. Normalized secant modulus, cross-sectional area and tendon glycosaminoglycan composition were inferior in OVX compared with females at 6 wk. Total fatigue cycles until tendon failure were similar among groups. Postinjury muscle fiber size was better preserved in females compared with males, and females had greater collagen III at the tendon injury site compared with males at 6 wk. Despite male and female Achilles tendons withstanding similar durations of fatigue loading, early passive hindlimb function and tendon mechanical properties, including secant modulus, suggest superior healing in females. Ovarian hormone loss was associated with inferior Achilles tendon healing.

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Sсherbak, Sergey G., Stanislav V. Makarenko, Olga V. Shneider, Tatyana A. Kamilova, and Alexander S. Golota. "Regenerative Rehabilitation in Injuries of Tendons." Physical and rehabilitation medicine, medical rehabilitation 3, no. 2 (July 5, 2021): 192–206. http://dx.doi.org/10.36425/rehab70760.

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The mechanical properties of tendons are thought to be affected by different loading levels. Changes in the mechanical properties of tendons, such as stiffness, have been reported to influence the risk of tendon injuries chiefly in athletes and the elderly, thereby affecting motor function execution. Unloading resulted in reduced tendons stiffness, and resistance exercise exercise counteracts this. Transforming growth factor-1 is a potent inducer of type I collagen and mechanosensitive genes encoding tenogenic differentiation markers expression which play critical roles in tendon tissue formation, tendon healing and their adaptation during exercise. In recent years, our understanding of the molecular biology of tendons growth and repair has expanded. It is probable that the next advance in the treatment of tendon injuries will result from the application of this basic science knowledge and the clinical solution will encompass not only the the best postoperative rehabilitation protocols, but also the optimal biological modulation of the healing process.

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HANFF, G., and S.-O. ABRAHAMSSON. "Matrix Synthesis and Cell Proliferation in Repaired Flexor Tendons within E-PTFE Reconstructed Flexor Tendon Sheaths." Journal of Hand Surgery 21, no. 5 (October 1996): 642–46. http://dx.doi.org/10.1016/s0266-7681(96)80149-5.

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Expanded polytetrafluoroethylene (e-PTFE) may be used as a barrier to reduce formation of restrictive adhesions following tendon surgery within the flexor tendon sheath region. In order to assess its effects on the cellular activity of healing tendons, synthesis and contents of matrix components and synthesis of DNA were compared in divided and sutured flexor tendons that either had been covered with e-PTFE membranes or with sham-operated tendon sheaths in 30 rabbits. At intervals of up to 12 weeks segments of the tendon repair sites were harvested, placed in wells and labelled with 35S-sulphate, 3H-proline and 3H-thymidine during short-term culture in vitro. Adverse tissue reactions and tendon disruptions were not observed at harvest. At each time interval synthesis of matrix components and DNA and contents of protein and collagen in the repaired tendon segments were similar in the two groups. Measured over all intervals, synthesis of non-collagen protein and contents of protein and collagen were lower in the e-PTFE groups. These results show that reconstruction of flexor tendon sheaths with e-PTFE membranes may not significantly impair cell proliferation but to some extent may reduce protein synthesis of healing tendons.

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Zhang, Jianying, Feng Li, Tyler Augi, Kelly M. Williamson, Kentaro Onishi, MaCalus V. Hogan, Matthew D. Neal, and James H. C. Wang. "Platelet HMGB1 in Platelet-Rich Plasma (PRP) promotes tendon wound healing." PLOS ONE 16, no. 9 (September 16, 2021): e0251166. http://dx.doi.org/10.1371/journal.pone.0251166.

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Platelet-rich plasma (PRP) is a widely used autologous treatment for tendon injuries in clinics. 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 of injured tissues; however, the contribution of PLT HMGB1 in wounded tendon healing remains unexplored. This study investigated the effect of PLT HMGB1 within PRP on tendon healing using PLT HMGB1 knockout (KO) 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 tendon wound healing by decreasing inflammation, increasing local HMGB1 levels, and recruiting stem cells to the wound area in the tendon. Our findings also suggest that the efficacy of PRP treatment for tendon injuries in clinics may depend on PLT HMGB1 within PRP preparations.

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Chisari, Emanuele, Laura Rehak, Wasim S. Khan, and Nicola Maffulli. "Tendon healing in presence of chronic low-level inflammation: a systematic review." British Medical Bulletin 132, no. 1 (December 2019): 97–116. http://dx.doi.org/10.1093/bmb/ldz035.

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Abstract Background Tendinopathy is a common musculoskeletal condition affecting subjects regardless of their activity level. Multiple inflammatory molecules found in ex vivo samples of human tendons are related to the initiation or progression of tendinopathy. Their role in tendon healing is the subject of this review. Sources of data An extensive review of current literature was conducted using PubMed, Embase and Cochrane Library using the term ‘tendon’, as well as some common terms of tendon conditions such as ‘tendon injury OR (tendon damage) OR tendonitis OR tendinopathy OR (chronic tendonitis) OR tendinosis OR (chronic tendinopathy) OR enthesitis’ AND ‘healing’ AND ‘(inflammation OR immune response)’ as either key words or MeSH terms. Areas of agreement An environment characterized by a low level of chronic inflammation, together with increased expression of inflammatory cytokines and growth factors, may influence the physiological tendon healing response after treatment. Areas of controversy Most studies on this topic exhibited limited scientific translational value because of their heterogeneity. The evidence associated with preclinical studies is limited. Growing points The role of inflammation in tendon healing is still unclear, though it seems to affect the overall outcome. A thorough understanding of the biochemical mediators of healing and their pathway of pain could be used to target tendinopathy and possibly guide its management. Areas timely for developing research We require further studies with improved designs to effectively evaluate the pathogenesis and progression of tendinopathy to identify cellular and molecular targets to improve outcomes.

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Forslund, Carina, and Per Aspenberg. "Improved Healing of Transected Rabbit Achilles Tendon after a Single Injection of Cartilage-Derived Morphogenetic Protein-2." American Journal of Sports Medicine 31, no. 4 (July 2003): 555–59. http://dx.doi.org/10.1177/03635465030310041301.

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Background Achilles tendon ruptures in humans might be treated more efficiently with the help of a growth factor. Cartilage-derived morphogenetic protein-2 has been shown to induce formation of tendon-like tissue. Hypothesis Cartilage-derived morphogenetic protein-2 has a positive effect on mechanical parameters for tendon healing in a rabbit model with Achilles tendon transection. Study Design Controlled laboratory study. Methods The right Achilles tendon of 40 rabbits was transected without tendon suture. Cartilage-derived morphogenetic protein-2 (10 μg) or vehicle control (acetate buffer) was injected locally 2 hours postoperatively. All tendons were tested biomechanically at 8 and 14 days, and treated tendons were histologically and radiographically evaluated at 56 days. Results At 14 days, both failure load and stiffness of treated tendons were increased by 35%. The treated tendons had significantly larger callus size at 8 and 14 days. Histologic and radiographic examination showed no signs of ossification in the treated tendons after 56 days. Conclusions A single injection of cartilage-derived morphogenetic protein-2 led to a stronger and stiffer tendon callus than that in the controls without inducing bone formation. Clinical Relevance Similar results from a larger animal model would suggest a possible future use of cartilage-derived morphogenetic protein-2 in the treatment of human Achilles tendon ruptures.

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Waldrop, Norman, Bonnie Mowry, Mitchell Sanders, and John McQuilling. "Application of Amniotic Membrane Improves Repair in a Diabetic Animal Model for Delayed Tendon Healing." Foot & Ankle Orthopaedics 2, no. 3 (September 1, 2017): 2473011417S0000. http://dx.doi.org/10.1177/2473011417s000082.

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Category: Basic Sciences/Biologics, Diabetes Introduction/Purpose: Tendon injuries often heal with significant scar formation and compromised biomechanical function. For diabetics, these injuries are further complicated by changes in the extracellular matrix of the tendon, leading to higher incidences of injury and slower healing. Defective or delayed healing is a result of several factors including an impaired ability to form a collagen matrix, compromised angiogenesis, and inadequate production of growth factors. Consequently, complications and re- rupture rates are higher in diabetic patients. Amnion-derived cells resulted in improved tendon healing in an otherwise healthy animal model, in part due to their ability to provide numerous regenerative cytokines to the repair site. The purpose of this study was to evaluate the effect of amniotic tissues on tendon healing in a diabetic model with impaired healing. Methods: For this study BBZDR/WOR animals, an insulin dependent Type II diabetic rodent model, were used. After appropriate anesthesia, a full thickness injury was made through the Achilles tendon; immediately following injury, the tendon was repaired using the modified Kessler method. Repaired tendons were wrapped with a 0.5 × 0.5 cm section of either a fresh hypothermically stored human amniotic membrane (HSAM), a dehydrated human amnion chorion membrane (dHACM), or left unwrapped as a control. Contralateral tendons were used as sham controls, which were exposed then immediately closed. Tendons were retrieved at 14 or 28 days and evaluated using histology, immunohistochemistry, and qPCR. At 28 days, both experimental tendons and contralateral controls from five rats per group were harvested and tested to failure and peak force, stiffness, energy uptake, and displacement at rupture were then determined. Results: At day 14, histological evaluation found significant increases in cellular recruitment at the site of injury in both dHACM and HSAM treated animals (p=0.0001). qPCR and immunofluorescence results confirmed several biomarkers implicated in tendon repair were highly expressed in the treatment groups, but not in untreated controls. In dHACM treated animals, TNF-a, TGFß-1, IL6, FLAP, Tenascin-C, and Scleraxis expression was elevated at 14 days. Control animals with only primary repair resulted in a tendon repair failure rate of 20%; whereas animals treated with HSAM or dHACM had a 6% and 0% failure rate, respectively. dHACM treated tendons also had significant improvements in biomechanical properties compared to controls including increases in the max force, stiffness and strain (47±21%, 146±90%, and 59±35% respectively). Conclusion: Augmentation of tendon repair with placental-derived membranes may improve diabetic tendon repair and reduce re-rupture rates. This study presents compelling data suggesting chorion-containing dHACM is more efficacious than the amnion- only HSAM for tendon repair. The cause for this difference is unclear, we hypothesize that cytokine content, important for tendon healing, within the chorion may be responsible. Components of placental tissue contribute different cytokines, ECM and cell populations—this study highlights that differences in components-delivered and processing techniques may impact outcomes and results may vary for different clinical applications. This study highlights a promising treatment option for a clinically challenging population.

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Journal articles on the topic 'Tendon healing'

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