Failure rate after chronic rotator cuff repair is considerably high. Moreover, diabetes mellitus is known as a compromising factor of rotator cuff tear. The effect of Polydeoxyribonucleotide (PDRN) and polynucleotide (PN) on tendon healing and fatty infiltration is unclear as tissue regeneration activator in diabetic state. Therefore, a diabetic rat model with chronic rotator cuff tear was made for mechanical, histologic and blood tests. In the animal study using a diabetic rat cuff repair model, the administration of PDRN and PN increased the load to failure of repaired cuffs and improved tendon healing and decreased fatty infiltration. Also, the plasma levels of vascular endothelial growth factor and fibroblast growth factor were elevated in PDRN and PN administrated groups. We concluded that PDRN and PN appear to boost tendon recovery and reduce the presence of fatty infiltration following cuff repair in diabetic state. Also, PN showed a later onset and a longer duration than PDRN associated with the mean plasma growth factors.

Successful tendon healing requires sufficient deposition and remodeling of new extracellular matrix at the site of injury, with this process mediating in part through fibroblast activation via communication with macrophages. Moreover, resolution of healing requires clearance or reversion of activated cells, with chronic interactions with persistent macrophages impairing resolution and facilitating the conversion the conversion to fibrotic healing. As such, modulation of the macrophage environment represents an important translational target to improve the tendon healing process. Circulating monocytes are recruited to sites of tissue injury, including the tendon, via upregulation of cytokines including Ccl2, which facilitates recruitment of Ccr2+ macrophages to the healing tendon. Our prior work has demonstrated that Ccr2-/- can modulate fibroblast activation and myofibroblast differentiation. However, this approach lacked temporal control and resulted in healing impairments. Thus, in the current study we have leveraged a Ccr2 antagonist to blunt macrophage recruitment to the healing tendon in a time-dependent manner. We first tested the effects of Ccr2 antagonism during the acute inflammatory phase and found that this had no effect on the healing process. In contrast, Ccr2 antagonism during the late inflammatory/ early proliferative period resulted in significant improvements in mechanical properties of the healing tendon. Collectively, these data demonstrate the temporally distinct impacts of modulating Ccr2+ cell recruitment and Ccr2 antagonism during tendon healing and highlight the translational potential of transient Ccr2 antagonism to improve the tendon healing process.

There is mounting evidence to suggest that exogenous electromagnetic fields (EMF) may play a significant role in various biological processes that are crucial to therapeutic interventions. EMFs have been identified as a non-invasive, safe, and effective therapy that appears to have no apparent side effects. Numerous studies have demonstrated that pulsed EMFs (PEMFs) have the potential to become a stand-alone or adjunctive treatment modality for managing musculoskeletal disorders. However, several questions remain unresolved. Before their widespread clinical application, further research from well-designed, high-quality studies is required to standardize treatment parameters and determine the optimal protocol for healthcare decision-making. This article provides a comprehensive overview of the impact of musculoskeletal diseases on overall well-being, the limitations of conventional treatments, and the need to explore alternative therapeutic modalities such as electromagnetic field (EMF) therapy. EMF therapy uses low-frequency electromagnetic waves to stimulate tissue repair, reduce inflammation, and modulate pain signals, making it a safe and convenient alternative to conventional treatments. The article also discusses the historical perspective of EMF therapy in medicine. The article highlights the potential of EMF therapy as a personalized and comprehensive care option for musculoskeletal diseases, either alone or in conjunction with other therapies. It emphasizes the imperative for further research in this field and presents a compelling case for the use of EMF therapy in managing musculoskeletal diseases. Overall, the available findings on the underlying cellular and molecular biology support the use of EMF therapy as a viable option for the management of musculoskeletal disorders and stresses the need for continued research in this area.

Tendon injury is a common disorder of the musculoskeletal system, with a higher possibility of occurrence in elderly individuals and athletes. After a tendon injury, the tendon suffers from inadequate and slow healing, resulting in the formation of fibrotic scar tissue, ending up with inferior functional properties. Therapeutic strategies involving the application of growth factors have been advocated to promote tendon healing. Growth and differentiation-5 (GDF-5) represents one such factor that has shown promising effect on tendon healing in animal models and in vitro cultures. Although promising, these studies are limited as the molecular mechanisms by which GDF-5 exerts its effect remain incompletely understood. Starting from broadly introducing essential elements of current understanding about GDF-5, the present review aims to define the effect of GDF-5 and its possible mechanisms of action in tendon healing. Nevertheless, we still need more in vivo studies to explore dosage, application time and delivery strategy of GDF-5, so as to pave the way for future clinical translation.

Tendon injuries are common orthopedic ailments with a challenging healing trajectory, especially in cases like the Achilles tendon afflictions. The healing trajectory of tendon injuries is often suboptimal, leading to scar formation and functional impairment due to the inherent low metabolic activity and vascularization of tendon tissue. As pressing is needed for effective interventions, efforts are made to explore biomaterials to augment tendon healing. However, tissue engineering approaches face hurdles in optimizing tissue scaffolds and nanomedical strategies. To navigate these challenges, an injectable hydrogel amalgamated with human umbilical vein endothelial cells-derived exosomes (HUVECs-Exos) was prepared and named H-Exos-gel in this study, aiming to enhance tendon repair. In our research involving a model of Achilles tendon injuries in 60 rats, we investigated the efficacy of H-Exos-gel through histological assessments performed at 2 and 4 weeks and behavioral assessments conducted at the 4-week mark revealed its ability to enhance the Achilles tendon\'s mechanical strength, regulate inflammation and facilitate tendon regeneration and functional recovery. Mechanically, the H-Exos-gel modulated the cellular behaviors of macrophages and tendon-derived stem cells (TDSCs) by inhibiting inflammation-related pathways and promoting proliferation-related pathways. Our findings delineate that the H-Exos-gel epitomizes a viable bioactive medium for tendon healing, heralding a promising avenue for the clinical amelioration of tendon injuries.

In the human body, ascorbic acid (AA) is known for its potent antioxidant and reducing properties and also plays a vital role in supporting the growth of bones and cartilage. It has been used extensively in orthopedic surgery. Ongoing studies under the umbrella of ascorbic acid research investigate its impact on bone and tendon physiology, as well as its influence on joint replacement and postoperative pain. The majority of both laboratory and human studies link the usage of ascorbic acid to enhanced bone health and improved tendon healing. Recent literature suggest that ascorbic acid administration may have a positive impact on the outcome of orthopedic procedures. On the other hand, controversy exists regarding the efficacy of ascorbic acid in reducing the incidence of complex regional pain syndrome. In brief, the effectiveness of ascorbic acid in enhancing orthopedic procedure outcomes remains a subject of ongoing investigation. Although certain studies have hinted at the potential positive influence of ascorbic acid on these outcomes, further research is required to validate its effectiveness and ascertain the ideal dosage and method of administration for maximizing its anticipated advantages. To establish the efficacy of ascorbic acid in improving orthopedic procedure outcomes, rigorous human trials of high quality are imperative. The aim of this review was to provide an overview of ascorbic acid\'s utilization in orthopedic practices and to pinpoint prospective areas for future research.

Acute rupture of the Achilles tendon (AT) is a common but debilitating injury that requires immediate diagnosis and effective management. Spontaneous bilateral AT rupture is rare; however, it can lead to severe disability for a significant period. This case report presents a 76-year-old patient who suffered a bilateral AT rupture while engaging in a non-strenuous activity. Upon confirmation of the diagnosis by physical examination and radiologic evaluation, conservative treatment was decided due to the presence of numerous comorbidities. A personalized rehabilitation protocol was implemented, allowing weight-bearing activities using Achilles boots at six weeks. Healing of both ATs was confirmed by an MRI at three months. Our case shows that non-operative treatment of these injuries can result in exceptionally favorable outcomes and should not be disregarded. However, thorough patient compliance and surveillance are prerequisites.

Tendon injuries, a common musculoskeletal issue, usually result in adhesions to the surrounding tissue, that will impact functional recovery. Macrophages, particularly through their M1 and M2 polarizations, play a pivotal role in the inflammatory and healing phases of tendon repair. In this review, we explore the role of macrophage polarization in tendon healing, focusing on insights from animal models. The review delves into the complex interplay of macrophages in tendon pathology, detailing how various macrophage phenotypes contribute to both healing and adhesion formation. It also explores the potential of modulating macrophage activity to enhance tendon repair and minimize adhesions. With advancements in understanding macrophage behavior and the development of innovative biomaterials, this review highlights promising therapeutic strategies for tendon injuries.

Rotator cuff tears are a condition characterized by damage to the muscles and tendons that connect the scapula and humerus, which are responsible for shoulder rotation and arm lifting. Metabolic factors such as diabetes, thyroid disease, high cholesterol, vitamin D deficiency, obesity, and smoking have been associated with an increased risk of rotator cuff tears. Interestingly, patients with hyperlipidemia, a condition characterized by high levels of cholesterol and other fats in the blood, have been found to have a higher incidence of rotator cuff tears and breakdown of tendon matrix. As a result, statin therapy, which is commonly used to lower cholesterol levels in hyperlipidemia, has been explored as a potential treatment to improve clinical outcomes in rotator cuff tears. However, the results of preclinical and clinical studies on the effects of statins on tendon healing in rotator cuff tears are limited and not well-defined. Moreover, since hyperlipidemia and rotator cuff tears are more prevalent in older individuals, a literature review on the efficacy and safety of statin therapy in this population is needed.

Tendon aging is associated with an increasing prevalence of tendon injuries and/or chronic tendon diseases, such as tendinopathy, which affects approximately 25% of the adult population. Aged tendons are often characterized by a reduction in the number and functionality of tendon stem/progenitor cells (TSPCs), fragmented or disorganized collagen bundles, and an increased deposition of glycosaminoglycans (GAGs), leading to pain, inflammation, and impaired mobility. Although the exact pathology is unknown, overuse and microtrauma from aging are thought to be major causative factors. Due to the hypovascular and hypocellular nature of the tendon microenvironment, healing of aged tendons and related injuries is difficult using current pain/inflammation and surgical management techniques. Therefore, there is a need for novel therapies, specifically cellular therapy such as cell rejuvenation, due to the decreased regenerative capacity during aging. To augment the therapeutic strategies for treating tendon-aging-associated diseases and injuries, a comprehensive understanding of tendon aging pathology is needed. This review summarizes age-related tendon changes, including cell behaviors, extracellular matrix (ECM) composition, biomechanical properties and healing capacity. Additionally, the impact of conventional treatments (diet, exercise, and surgery) is discussed, and recent advanced strategies (cell rejuvenation) are highlighted to address aged tendon healing. This review underscores the molecular and cellular linkages between aged tendon biomechanical properties and the healing response, and provides an overview of current and novel strategies for treating aged tendons. Understanding the underlying rationale for future basic and translational studies of tendon aging is crucial to the development of advanced therapeutics for tendon regeneration.