Human platelet lysate - A potent (and overlooked) orthobiologic.

The knowledge of the essential role of platelets in tissue healing is gradually increasing and as regenerative medicine prompts new solutions, platelet-derived bioproducts have been proposed as a potential tool in this field. In orthopaedics and sports medicine, the use of PRP has been rapidly increasing in popularity as patients seek novel non-surgical approaches to acute and chronic musculoskeletal conditions. The concept of having platelets as a secretory organ other than a mere sponge-like coagulation component opens up new frontiers for the use of the platelet secretome. Platelet lysate is a solution saturated by growth factors, proteins, cytokines, and chemokines involved in crucial healing processes and is administered to treat different diseases such as alopecia, oral mucositis, radicular pain, osteoarthritis, and cartilage and tendon disorders. For this purpose, the abundant presence of growth factors and chemokines stored in platelet granules can be naturally released by different strategies, mostly through lyophilization, thrombin activation or ultrasound baths (ultrasonication). As a result, human platelet lysate can be produced and applied as a pure orthobiologic. This review outlines the current knowledge about human platelet lysate as a powerful adjuvant in the orthobiological use for the treatment of musculoskeletal injuries, without however failing to raise some of its most applicable basic science.

The protective role of glutathione in osteoarthritis.

It is currently understood that osteoarthritis (OA) is a major chronic inflammatory musculoskeletal disease. While this disease has long been attributed to biomechanical trauma, recent evidence establishes a significant correlation between osteoarthritic progression and unbridled oxidative stress, responsible for prolonged inflammation. Research describes this as a disturbance in the balanced production of reactive oxygen species (ROS) and antioxidant defenses, generating macromolecular damage and disrupted redox signaling and control. Since ROS pathways are being considered new targets for OA treatment, the development of antioxidant therapy to counteract exacerbated oxidative stress is being continuously researched and enhanced in order to fortify the cellular defenses. Experiments with glutathione and its precursor molecule, N-acetylcysteine (NAC), have shown interesting results in the literature for the management of OA, where they have demonstrated efficacy in reducing cartilage degradation and inflammation markers as well as significant improvements in pain and functional outcomes. Glutathione remains a safe, effective and overall cheap treatment alternative in comparison to other current therapeutic solutions and, for these reasons, it may prove to be comparably superior under particular circumstances. METHODS: Literature was reviewed using PubMed and Google Scholar in order to bring up significant evidence and illustrate the defensive mechanisms of antioxidant compounds against oxidative damage in the onset of musculoskeletal diseases. The investigation included a combination of keywords such as: oxidative stress, oxidative damage, inflammation, osteoarthritis, antioxidant, glutathione, n-acetylcysteine, redox, and cell signaling. CONCLUSION: Based on the numerous studies included in this literature review, glutathione and its precursor N-acetylcysteine have demonstrated significant protective effects in events of prolonged, exacerbated oxidative stress as seen in chronic inflammatory musculoskeletal disorders such as osteoarthritis.

Nebulization of glutathione and N-Acetylcysteine as an adjuvant therapy for COVID-19 onset.

Ever since its emergence, the highly transmissible and debilitating coronavirus disease spread at an incredibly fast rate, causing global devastation in a matter of months. SARS-CoV-2, the novel coronavirus responsible for COVID-19, infects hosts after binding to ACE2 receptors present on cells from many structures pertaining to the respiratory, cardiac, hematological, neurological, renal and gastrointestinal systems. COVID-19, however, appears to trigger a severe cytokine storm syndrome in pulmonary structures, resulting in oxidative stress, exacerbated inflammation and alveolar injury. Due to the recent nature of this disease no treatments have shown complete efficacy and safety. More recently, however, researchers have begun to direct some attention towards GSH and NAC. These natural antioxidants play an essential role in several biological processes in the body, especially the maintenance of the redox equilibrium. In fact, many diseases appear to be strongly related to severe oxidative stress and deficiency of endogenous GSH. The high ratios of ROS over GSH, in particular, appear to reflect severity of symptoms and prolonged hospitalization of COVID-19 patients. This imbalance interferes with the body's ability to detoxify the cellular microenvironment, fold proteins, replenish antioxidant levels, maintain healthy immune responses and even modulate apoptotic events. Oral administration of GSH and NAC is convenient and safe, but they are susceptible to degradation in the digestive tract. Considering this drawback, nebulization of GSH and NAC as an adjuvant therapy may therefore be a viable alternative for the management of the early stages of COVID-19.

Bone marrow aspirate clot: A feasible orthobiologic.

Musculoskeletal disorders are one of the major health burdens and a leading source of disability worldwide, affecting both juvenile and elderly populations either as a consequence of ageing or extrinsic factors such as physical injuries. This condition often involves a group of locomotor structures such as the bones, joints and muscles and may therefore cause significant economic and emotional impact. Some pharmacological and non-pharmacological treatments have been considered as potential solutions, however, these alternatives have provided quite limited efficacy due to the short-term effect on pain management and inability to restore damaged tissue. The emergence of novel therapeutic alternatives such as the application of orthobiologics, particularly bone marrow aspirate (BMA) clot, have bestowed medical experts with considerable optimism as evidenced by the significant results found in numerous studies addressed in this manuscript. Although other products have been proposed for the treatment of musculoskeletal injuries, the peculiar interest in BMA, fibrin clot and associated fibrinolytic mechanisms continues to expand. BMA is a rich source of various cellular and molecular components which have demonstrated positive effects on tissue regeneration in many in vitro and in vivo models of musculoskeletal injuries. In addition to being able to undergo self-renewal and differentiation, the hematopoietic and mesenchymal stem cells present in this orthobiologic elicit key immunomodulatory and paracrine roles in inflammatory responses in tissue injury and drive the coagulation cascade towards tissue repair via different mechanisms. Although promising, these complex regenerative mechanisms have not yet been fully elucidated.