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Tendon injury accounts for 30% of musculoskeletal diseases and often leads to disability, pain, healthcare cost, and lost productivity. Following injury to tendon, tendon healing proceeds via three overlapping healing processes. However, due to the structural defects of the tendon itself, the tendon healing process is characterized by the formation of excessive fibrotic scar tissue, and injured tendons rarely return to native tendons, which can easily contribute to tendon reinjury. Moreover, the resulting fibrous scar is considered to be a precipitating factor for subsequent degenerative tendinopathy. Despite this, therapies are almost limited because underlying molecular mechanisms during tendon healing are still unknown. Transforming Growth Factor-β1 (TGF-β1) is known as one of most potent profibrogenic factors during tendon healing process. However, blockage TGF-β1 fails to effectively enhance tendon healing. A detailed understanding of real abilities of TGF-β1 involved in tendon healing can bring promising perspectives for therapeutic value that improve the tendon healing process. Thus, in this review, we describe recent efforts to identify and characterize the roles and mechanisms of TGF-β1 involved at each stage of the tendon healing and highlight potential roles of TGF-β1 leading to the fibrotic response to tendon injury., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Tendon injury is a common disorder of the musculoskeletal system caused by overuse or trauma. With increasing incidence of tendon injuries, it is necessary to find an effective treatment. Mesenchymal stem cells (MSCs) are attracting attention because of their high proliferative and self‑renewal capacity. These functions of MSCs show promise in treating a variety of diseases, including immune and musculoskeletal system disorder and cardiovascular disease, and show especially satisfactory effects in the treatment of tendon injury. First, since MSCs have multidirectional differentiation potential, they differentiate into specific cells after induction in vivo and in vitro . Furthermore, MSCs have paracrine functions and can secrete biologically active molecules and exosomes such as cytokines, growth factors and chemokines to promote tissue repair and regeneration. In tendon injury, MSCs promote tendon repair through four mechanisms: Decreasing inflammation and promoting neovascularization and cell proliferation and differentiation. They are also involved in extracellular matrix reorganization by promoting collagen production and transforming type III collagen fibers to type I collagen fibers. The present review summarized preclinical experiments with different sources of MSCs and their mechanisms in tendon repair, as well as the limitations of MSCs in current clinical applications and directions that need to be explored in the future.

Tendon injury is one of the most common disorders of the musculoskeletal system, with a higher likelihood of occurrence in elderly individuals and athletes. In posthealing tendons, two undesirable consequences, tissue fibrosis and a reduction in mechanical properties, usually occur, resulting in an increased probability of rerupture or reinjury; thus, it is necessary to propose an appropriate treatment. Currently, most methods do not sufficiently modulate the tendon healing process and restore the function and structure of the injured tendon to those of a normal tendon, since there is still inadequate information about the effects of multiple cellular and other relevant signaling pathways on tendon healing and how the expression of their components is regulated. microRNAs are vital targets for promoting tendon repair and can modulate the expression of biological components in signaling pathways involved in various physiological and pathological responses. miRNAs are a type of noncoding ribonucleic acid essential for regulating processes such as cell proliferation, differentiation, migration and apoptosis; inflammatory responses; vascularization; fibrosis; and tissue repair. This article focuses on the biogenesis response of miRNAs while presenting their mechanisms in tendon healing with perspectives and suggestions., (© 2023. The Author(s).)

Tendon injuries are widespread and chronic disorders of the musculoskeletal system, frequently caused by overload of the tendons. Currently, the most common treatment for tendon injuries is "cell-free therapy", of which exosomes, which can treat a host of diseases, including immune disorders, musculoskeletal injuries and cardiovascular diseases, are one kind. Among the many sources of exosomes, adipose-derived stem cell exosomes (ASC-Exos) have better efficacy. This is attributed not only to the ease of isolation of adipose tissue, but also to the high differentiation capacity of ASCs, their greater paracrine function, and immunomodulatory capacity compared to other exosomes. ASC-Exos promote tendon repair by four mechanisms: promoting angiogenesis under hypoxic conditions, reducing the inflammatory response, promoting tendon cell migration and proliferation, and accelerating collagen synthesis, thus accelerating tendon healing. This review focuses on describing studies of preclinical experiments with various exosomes, the characteristics of ASC-Exos and their mechanisms of action in tendon healing, as well as elaborating the limitations of ASC-Exos in clinical applications., (© 2022. The Author(s).)

Tendon injury is one of the prevalent disorders of the musculoskeletal system in orthopedics and is characterized by pain and limitation of joint function. Due to the difficulty of spontaneous tendon healing, and the scar tissue and low mechanical properties that usually develops after healing. Therefore, the healing of tendon injury remains a clinical challenge. Although there are a multitude of approaches to treating tendon injury, the therapeutic effects have not been satisfactory to date. Recent studies have shown that stem cell therapy has a facilitative effect on tendon healing. In particular, tendon stem/progenitor cells (TSPCs), a type of stem cell from tendon tissue, play an important role not only in tendon development and tendon homeostasis, but also in tendon healing. Compared to other stem cells, TSPCs have the potential to spontaneously differentiate into tenocytes and express higher levels of tendon-related genes. TSPCs promote tendon healing by three mechanisms: modulating the inflammatory response, promoting tenocyte proliferation, and accelerating collagen production and balancing extracellular matrix remodeling. However, current investigations have shown that TSPCs also have a negative effect on tendon healing. For example, misdifferentiation of TSPCs leads to a "failed healing response," which in turn leads to the development of chronic tendon injury (tendinopathy). The focus of this paper is to describe the characteristics of TSPCs and tenocytes, to demonstrate the roles of TSPCs in tendon healing, while discussing the approaches used to culture and differentiate TSPCs. In addition, the limitations of TSPCs in clinical application and their potential therapeutic strategies are elucidated. [ABSTRACT FROM AUTHOR]

Tendon injuries are one of the most common musculoskeletal disorders for which patients seek medical aid, reducing not only the quality of life of the patient but also imposing a significant economic burden on society. The administration of growth factors at the wound site is a feasible solution for enhancing tendon healing. Platelet-derived growth factor-BB (PDGF-BB) has a well-defined safety profile compared to other growth factors and has been approved by the Food and Drug Administration (FDA). The purpose of this review is to summarize the role of PDGF-BB in tendon healing through a comprehensive review of the published literature. Experimental studies suggest that PDGF-BB has a positive effect on tendon healing by enhancing inflammatory responses, speeding up angiogenesis, stimulating tendon cell proliferation, increasing collagen synthesis and increasing the biomechanics of the repaired tendon. PDGF-BB is regarded as a promising candidate in tendon healing. However, in order to realize its full potential, we still need to carefully consider and study key issues such as dose and application time in the future, so as to explore further applications of PDGF-BB in the tendon healing process. [ABSTRACT FROM AUTHOR]

Tendon injury is a disorder of the musculoskeletal system caused by overuse or trauma, which is characterized by pain and limitations in joint function. Since tendon healing is slowly and various treatments are generally ineffective, it remains a clinically challenging problem. Recent evidences suggest that basic fibroblast growth factor (bFGF) not only plays an important role in tendon healing, but also shows a positive effect in laboratory experimentations. The purpose of this review is to summarize the effects of bFGF in the tendon healing. Firstly, during the inflammatory phase, bFGF stimulates the proliferation and differentiation of vascular endothelial cells to foster neovascularization. Furthermore, bFGF enhances the production of pro-inflammatory factors during the early phase of tendon healing, thereby accelerating the inflammatory response. Secondly, the cell proliferation phase is accompanied by the synthesis of a large number of extracellular matrix components. bFGF speeds up tendon healing by stimulating fibroblasts to secrete type III collagen. Lastly, the remodeling phase is characterized by the transition from type III collagen to type I collagen, which can be promoted by bFGF. However, excessive injection of bFGF can cause tendon adhesions as well as scar tissue formation. In future studies, we need to explore further applications of bFGF in the tendon healing process. [ABSTRACT FROM AUTHOR]

Tendon injury is a common disease of the musculoskeletal system, accounting for roughly 30%–40% of sports system disorder injuries. In recent years, its incidence is increasing. Many studies have shown that low-level laser therapy (LLLT) has a significant effect on tendon repair by firstly activating cytochrome C oxidase and thus carrying out the photon absorption process, secondly acting in all the three phases of tendon repair, and finally improving tendon recovery. The repair mechanisms of LLLT are different in the three phases of tendon repair. In the inflammatory phase, LLLT mainly activates a large number of VEGF and promotes angiogenesis under hypoxia. During the proliferation phase, LLLT increases the amount of collagen type III by promoting the proliferation of fibroblasts. Throughout the remodeling phase, LLLT mainly activates M2 macrophages and downregulates inflammatory factors, thus reducing inflammatory responses. However, it should also be noted that in the final phase of tendon repair, the use of LLLT causes excessive upregulation of some growth factors, which will lead to tendon fibrosis. In summary, we need to further investigate the functions and mechanisms of LLLT in the treatment of tendon injury and to clarify the nature of LLLT for the treatment of diverse tendon injury diseases. [ABSTRACT FROM AUTHOR]