Preparing the soil: Adjusting the metabolic health of patients with chronic wounds and musculoskeletal diseases.

In recent years, systemic inflammation has emerged as a pivotal player in the development and progression of various degenerative diseases. This complex, chronic inflammatory state, often undetected, can have far-reaching consequences for the body's physiology. At the molecular level, markers such as C-reactive protein, cytokines and other inflammatory mediators serve as indicators of systemic inflammation and often act as predictors of numerous musculoskeletal diseases and even certain forms of cancer. The concept of 'meta-inflammation', specifically referring to metabolically triggered inflammation, allows healthcare professionals to understand inflammatory responses in patients with metabolic syndrome. Driven by nutrient excess and the expansion of adipose tissue, meta-inflammation is closely associated with insulin resistance, further propagating the metabolic dysfunction observed in many Western societies. Wound persistence, on the other hand, exacerbates the detrimental effects of prolonged inflammation at the local level. Acute inflammation is a beneficial and essential process for wound healing and infection control. However, when inflammation fails to resolve, it can impede the healing process, leading to chronic wounds, excessive scarring and even the activation of fibrotic pathways. This approach significantly reduces the efficacy of regenerative biological therapies. Our review focuses on the vital role of proteins, vitamins and minerals in collagen synthesis and cell proliferation for tissue healing. We also examine hormonal influences on regeneration, noting the negative effects of imbalances, and emphasize glucose regulation's importance in creating a stable environment for chronic wound healing.

The role of orthobiologics in chronic wound healing.

Chronic wounds, characterized by prolonged healing processes, pose a significant medical challenge with multifaceted aetiologies, including local and systemic factors. Here, it explores the complex pathogenesis of chronic wounds, emphasizing the disruption in the normal phases of wound healing, particularly the inflammatory phase, leading to an imbalance in extracellular matrix (ECM) dynamics and persistent inflammation. Senescent cell populations further contribute to impaired wound healing in chronic lesions. Traditional medical management focuses on addressing underlying causes, but many chronic wounds resist to conventional treatments, necessitating innovative approaches. Recent attention has turned to autologous orthobiologics, such as platelet-rich plasma (PRP), platelet-rich fibrin (PRF) and mesenchymal stem cells (MSCs), as potential regenerative interventions. These biologically derived materials, including bone marrow aspirate/concentrate (BMA/BMAC) and adipose tissue-derived stem cells (ADSCs), exhibit promising cytokine content and regenerative potential. MSCs, in particular, have emerged as key players in wound healing, influencing inflammation and promoting tissue regeneration. This paper reviews relevant scientific literature regarding basic science and brings real-world evidence regarding the use of orthobiologics in the treatment of chronic wounds, irrespective of aetiology. The discussion highlights the regenerative properties of PRP, PRF, BMA, BMAC and SVF, showcasing their potential to enhance wound healing. Despite advancements, further research is essential to elucidate the specific roles of each orthobiologic and determine optimal applications for different wound types. The conclusion underscores the evolving landscape in chronic wound management, with a call for more comprehensive studies to refine treatment strategies and maximize the benefits of regenerative medicine.

Bone Marrow Aspirate Concentrate Improves Outcomes in Adults With Osteochondral Dissecans of the Talus and Achilles Rupture.

PURPOSE: The objective of this systematic literature review was to investigate the effects of the clinical application of bone marrow aspirate (BMA) and/or bone marrow aspirate concentrate (BMAC) in tendon and cartilage injuries in the foot and ankle. METHODS: A search of the Embase, MEDLINE/PubMed, CINAHL, and Cochrane databases was performed in January 2021. The risk of bias of the studies was assessed using the tool "A Cochrane Risk of Bias Assessment Tool for Non-Randomized Studies." The outcomes analyzed included pain reduction and functional improvement with the use of BMA/BMAC in patients with tendon and cartilage injuries in the foot and ankle. RESULTS: Eleven studies met the inclusion criteria for analysis, involving a total of 527 subjects with osteochondral lesions (OCLs) of the talus, cartilage lesions of the talus, and acute Achilles tendon rupture. BMAC was applied alone in 4 studies, and in 7 studies, it was compared with other techniques such as matrix-induced autologous chondrocyte implantation, particulate juvenile articular cartilage, or microfracture. Interventions demonstrated improved function and reduced foot and ankle pain and showed no serious adverse effects. CONCLUSIONS: Evidence indicates that BMAC provides good clinical results, with improved function and reduced pain in adults with OCL and cartilage lesions of the talus and acute Achilles tendon rupture. LEVEL OF EVIDENCE: Level IV, systematic review of level II to IV studies.

The Mechanism of Action between Pulsed Radiofrequency and Orthobiologics: Is There a Synergistic Effect?

Radiofrequency energy is a common treatment modality for chronic pain. While there are different forms of radiofrequency-based therapeutics, the common concept is the generation of an electromagnetic field in the applied area, that can result in neuromodulation (pulsed radiofrequency-PRF) or ablation. Our specific focus relates to PRF due to the possibility of modulation that is in accordance with the mechanisms of action of orthobiologics. The proposed mechanism of action of PRF pertaining to pain relief relies on a decrease in pro-inflammatory cytokines, an increase in cytosolic calcium concentration, a general effect on the immune system, and a reduction in the formation of free radical molecules. The primary known properties of orthobiologics constitute the release of growth factors, a stimulus for endogenous repair, analgesia, and improvement of the function of the injured area. In this review, we described the mechanism of action of both treatments and pertinent scientific references to the use of the combination of PRF and orthobiologics. Our hypothesis is a synergic effect with the combination of both techniques which could benefit patients and improve the life quality.

The Association between Gut Microbiota and Osteoarthritis: Does the Disease Begin in the Gut?

Some say that all diseases begin in the gut. Interestingly, this concept is actually quite old, since it is attributed to the Ancient Greek physician Hippocrates, who proposed the hypothesis nearly 2500 years ago. The continuous breakthroughs in modern medicine have transformed our classic understanding of the gastrointestinal tract (GIT) and human health. Although the gut microbiota (GMB) has proven to be a core component of human health under standard metabolic conditions, there is now also a strong link connecting the composition and function of the GMB to the development of numerous diseases, especially the ones of musculoskeletal nature. The symbiotic microbes that reside in the gastrointestinal tract are very sensitive to biochemical stimuli and may respond in many different ways depending on the nature of these biological signals. Certain variables such as nutrition and physical modulation can either enhance or disrupt the equilibrium between the various species of gut microbes. In fact, fat-rich diets can cause dysbiosis, which decreases the number of protective bacteria and compromises the integrity of the epithelial barrier in the GIT. Overgrowth of pathogenic microbes then release higher quantities of toxic metabolites into the circulatory system, especially the pro-inflammatory cytokines detected in osteoarthritis (OA), thereby promoting inflammation and the initiation of many disease processes throughout the body. Although many studies link OA with GMB perturbations, further research is still needed.

The regenerative mechanisms of platelet-rich plasma: A review.

Orthobiologics continue to gain popularity in many areas of medical science, especially in the field of regenerative medicine. Platelet-rich plasma derivatives are orthobiologic tools of particular interest. These biologic products can be obtained via centrifugation of a patient's whole blood and the components can then be subsequently isolated, concentrated and ultimately administered into injured tissues, particularly in areas where standard healing is disrupted. The elevated concentration of platelets above the basal value enables accelerated growth of various tissues with minimal side effects. The application of autologous orthobiologics is a relatively new biotechnology undergoing expansion which continues to reveal optimistic results in the stimulation and enhanced healing of various sorts of tissue injuries. The local release of growth factors and cytokines contained in platelet alpha granules accelerates and ameliorates tissue repair processes, mimicking and supporting standard wound healing. This effect is greatly enhanced upon combination with the fibrinolytic system, which are essential for complete regeneration. Fibrinolytic reactions can dictate proper cellular recruitment of certain cell populations such as mesenchymal stem cells and other immunomodulatory agents. Additionally, these reactions also control proteolytic activity in areas of wound healing and regenerative processes of mesodermal tissues including bone, cartilage, and muscle, which makes it particularly valuable for musculoskeletal health, for instance. Although many investigations have demonstrated significant results with platelet-rich plasma derivatives, further studies are still warranted.

Bone Marrow Aspirate Matrix: A Convenient Ally in Regenerative Medicine.

The rise in musculoskeletal disorders has prompted medical experts to devise novel effective alternatives to treat complicated orthopedic conditions. The ever-expanding field of regenerative medicine has allowed researchers to appreciate the therapeutic value of bone marrow-derived biological products, such as the bone marrow aspirate (BMA) clot, a potent orthobiologic which has often been dismissed and regarded as a technical complication. Numerous in vitro and in vivo studies have contributed to the expansion of medical knowledge, revealing optimistic results concerning the application of autologous bone marrow towards various impactful disorders. The bone marrow accommodates a diverse family of cell populations and a rich secretome; therefore, autologous BMA-derived products such as the "BMA Matrix", may represent a safe and viable approach, able to reduce the costs and some drawbacks linked to the expansion of bone marrow. BMA provides -it eliminates many hurdles associated with its preparation, especially in regards to regulatory compliance. The BMA Matrix represents a suitable alternative, indicated for the enhancement of tissue repair mechanisms by modulating inflammation and acting as a natural biological scaffold as well as a reservoir of cytokines and growth factors that support cell activity. Although promising, more clinical studies are warranted in order to further clarify the efficacy of this strategy.

Outcomes of flexor digitorum longus (FDL) tendon transfer in the treatment of Achilles tendon disorders.

BACKGROUND: In patients with chronic Achilles tendon disorders, Achilles tendon debridement can be supplemented with a tendon transfer, with the flexor hallucis longus tendon (FHL) transfer representing the most common used technique. Our study describes clinical and functional results of patients treated with flexor digitorum longus (FDL) tendon transfer in the treatment of patients with chronic Achilles tendon disorders. METHODS: Retrospective study of prospectively collected data of thirteen patients (15 feet) that underwent FDL tendon transfer as part of the treatment of chronic Achilles tendon disorders. Preoperative and postoperative assessment included visual analogue score (VAS) for pain, SF-36 survey and lower extremity functional scale (LEFS). The average follow-up was 26.4 (range, 14-56) months. Patients were also assessed for ability to perform single leg heel rise test, muscle power for plantar flexion of the lesser toes, surgical scar condition and associated complications. RESULTS: At final follow-up, we found significant postoperative improvement in VAS score (6.6 ±â€¯2.99 vs 1.06 ±â€¯1.43; p < .0001), SF-36 physical component summary (PCS) (28.20 ±â€¯10.71 vs 45.04 ±â€¯11.19; p < .0001) and LEFS (36.13 ±â€¯20.49 vs 58.73 ±â€¯18.19; p < .0001). Twelve patients (92%) could perform a single leg heel rise test in the operated extremity, although there was significant difference when comparing operated and uninvolved sides (4.86 ±â€¯3.36 cm vs 7.18 ±â€¯3.40 cm; p = .0002). One patient reported weakness for plantar flexion of the lesser toes, without balance or gait disturbances. Two patients (2 feet, 13.3%) had superficial infections and one patient (one foot, 6.6%) needed operative debridement for a deep infection. CONCLUSIONS: FDL tendon transfer represent an operative alternative in the treatment of chronic Achilles tendon disorders. Our study showed good clinical outcomes with low complications and donor site morbidity. LEVEL OF EVIDENCE: Observational study, case series - level IV.

Metal artifact reduction MRI for total ankle replacement sagittal balance evaluation.

BACKGROUND: Restoration of anatomical relationship between talus and tibia is crucial for longevity of total ankle replacement (TAR). Weight-bearing (WB) radiographs are the standard for evaluating the sagittal balance alignment, but are prone to rotational misalignment and altered measurements. Metal artifact reduction sequence (MARS) MRI allows visualization of periprosthetic landmarks and alignment of the image plane to the true sagittal axis of the implant. The purpose of this study was to compare TAR sagittal balance measurements on MARS MRI and WB radiographs. METHODS: Twenty-three subjects with TAR [10 men/13 women, age 60 (41-73) years; 13 (3-24) months post-op] underwent MARS MRI and standard lateral WB radiographs. Standardized MARS MR images were aligned to the sagittal talar component axis. Three observers performed sagittal balance alignment measurements twice in an independent, random and blinded fashion. Lateral Talar Station (LTS), tibial axis-to-talus (T-T) ratio and normalized tibial axis-to-lateral-process (T-L) distance were measured. Concordance correlation coefficients (CCC) and intraclass correlation coefficients (ICC) were used for statistical analysis. In addition, mixed effects linear models were employed to assess overall concordance of the two image types. RESULTS: The intraobserver agreement was excellent for radiographic (CCC=0.96) and MRI (CCC=0.90-0.97) measurements. Interobserver agreements were good-to-excellent with overall slightly higher agreements for MRI (ICC=0.78-0.94) than radiography (ICC=0.78-0.90) measurements. The T-T ratios of radiographs and MRI showed a high degree of concordance, whereas LTS was significantly lower on MRI when compared with radiographs, and T-L distance showed notable disagreement between the two imaging types. CONCLUSION: Sagittal balance measurements performed on standardized weight-bearing radiographs and standardized MARS MRI demonstrate substantial correlation and similarity. Given its high intra and interobserver agreement, MARS MRI may be helpful for the evaluation of TAR sagittal balance. LEVEL OF EVIDENCE: Level II - Prospective Comparative Study.

☆Diagnostic and therapeutic injections of the foot and ankle-An overview.

Foot and ankle injections are useful diagnostic and therapeutic tools, particularly when the pain etiology is uncertain. A variety of foot and ankle injuries and pathologies, including degenerative joint disease, plantar fasciitis and different tendinopathies are amenable to injections. Understanding the foot and ankle anatomical landmarks, a thorough physical exam and knowledge of the different injection techniques is key for a successful approach to different pathologies. The objective of this study is to review the use of foot and ankle injections in the orthopaedic literature, present the readers with the senior author's experience and provide a comprehensive clinical guideline to the most common foot and ankle diagnostic and therapeutic injections.

Gut microbiome: A revolution in type II diabetes mellitus.

Type II diabetes mellitus (T2DM) has experienced a dramatic increase globally across countries of various income levels over the past three decades. The persistent prevalence of T2DM is attributed to a complex interplay of genetic and environmental factors. While numerous pharmaceutical therapies have been developed, there remains an urgent need for innovative treatment approaches that offer effectiveness without significant adverse effects. In this context, the exploration of the gut microbiome presents a promising avenue. Research has increasingly shown that the gut microbiome of individuals with T2DM exhibits distinct differences compared to healthy individuals, suggesting its potential role in the disease's pathogenesis and progression. This emerging field offers diverse applications, particularly in modifying the gut environment through the administration of prebiotics, probiotics, and fecal microbiome transfer. These inter-ventions aim to restore a healthy microbiome balance, which could potentially alleviate or even reverse the metabolic dysfunctions associated with T2DM. Although current results from clinical trials have not yet shown dramatic effects on diabetes management, the groundwork has been laid for deeper investigation. Ongoing and future clinical trials are critical to advancing our understanding of the microbiome's impact on diabetes. By further elucidating the mechanisms through which microbiome alterations influence insulin resistance and glucose metabolism, researchers can develop more targeted interventions. The potential to harness the gut microbiome in developing new therapeutic strategies offers a compelling prospect to transform the treatment landscape of T2DM, potentially reducing the disease's burden significantly with approaches that are less reliant on traditional pharmaceuticals and more focused on holistic, systemic health improvements.

Sacral Bioneuromodulation: The Role of Bone Marrow Aspirate in Spinal Cord Injuries.

Spinal cord injury (SCI) represents a severe trauma to the nervous system, leading to significant neurological damage, chronic inflammation, and persistent neuropathic pain. Current treatments, including pharmacotherapy, immobilization, physical therapy, and surgical interventions, often fall short in fully addressing the underlying pathophysiology and resultant disabilities. Emerging research in the field of regenerative medicine has introduced innovative approaches such as autologous orthobiologic therapies, with bone marrow aspirate (BMA) being particularly notable for its regenerative and anti-inflammatory properties. This review focuses on the potential of BMA to modulate inflammatory pathways, enhance tissue regeneration, and restore neurological function disrupted by SCI. We hypothesize that BMA's bioactive components may stimulate reparative processes at the cellular level, particularly when applied at strategic sites like the sacral hiatus to influence lumbar centers and higher neurological structures. By exploring the mechanisms through which BMA influences spinal repair, this review aims to establish a foundation for its application in clinical settings, potentially offering a transformative approach to SCI management that extends beyond symptomatic relief to promoting functional recovery.

Platelet-Rich Plasma Power-Mix Gel (ppm)-An Orthobiologic Optimization Protocol Rich in Growth Factors and Fibrin.

Platelet- and fibrin-rich orthobiologic products, such as autologous platelet concentrates, have been extensively studied and appreciated for their beneficial effects on multiple conditions. Platelet-rich plasma (PRP) and its derivatives, including platelet-rich fibrin (PRF), have demonstrated encouraging outcomes in clinical and laboratory settings, particularly in the treatment of musculoskeletal disorders such as osteoarthritis (OA). Although PRP and PRF have distinct characteristics, they share similar properties. The relative abundance of platelets, peripheral blood cells, and molecular components in these orthobiologic products stimulates numerous biological pathways. These include inflammatory modulation, augmented neovascularization, and the delivery of pro-anabolic stimuli that regulate cell recruitment, proliferation, and differentiation. Furthermore, the fibrinolytic system, which is sometimes overlooked, plays a crucial role in musculoskeletal regenerative medicine by regulating proteolytic activity and promoting the recruitment of inflammatory cells and mesenchymal stem cells (MSCs) in areas of tissue regeneration, such as bone, cartilage, and muscle. PRP acts as a potent signaling agent; however, it diffuses easily, while the fibrin from PRF offers a durable scaffolding effect that promotes cell activity. The combination of fibrin with hyaluronic acid (HA), another well-studied orthobiologic product, has been shown to improve its scaffolding properties, leading to more robust fibrin polymerization. This supports cell survival, attachment, migration, and proliferation. Therefore, the administration of the "power mix" containing HA and autologous PRP + PRF may prove to be a safe and cost-effective approach in regenerative medicine.

Cannabidiol for musculoskeletal regenerative medicine.

Chronic musculoskeletal (MSK) pain is one of the most prevalent causes, which lead patients to a physician's office. The most common disorders affecting MSK structures are osteoarthritis, rheumatoid arthritis, back pain, and myofascial pain syndrome, which are all responsible for major pain and physical disability. Although there are many known management strategies currently in practice, phytotherapeutic compounds have recently begun to rise in the medical community, especially cannabidiol (CBD). This natural, non-intoxicating molecule derived from the cannabis plant has shown interesting results in many preclinical studies and some clinical settings. CBD plays vital roles in human health that go well beyond the classic immunomodulatory, anti-inflammatory, and antinociceptive properties. Recent studies demonstrated that CBD also improves cell proliferation and migration, especially in mesenchymal stem cells (MSCs). The foremost objective of this review article is to discuss the therapeutic potential of CBD in the context of MSK regenerative medicine. Numerous studies listed in the literature indicate that CBD possesses a significant capacity to modulate mammalian tissue to attenuate and reverse the notorious hallmarks of chronic musculoskeletal disorders (MSDs). The most of the research included in this review report common findings like immunomodulation and stimulation of cell activity associated with tissue regeneration, especially in human MSCs. CBD is considered safe and well tolerated as no serious adverse effects were reported. CBD promotes many positive effects which can manage detrimental alterations brought on by chronic MSDs. Since the application of CBD for MSK health is still undergoing expansion, additional randomized clinical trials are warranted to further clarify its efficacy and to understand its cellular mechanisms.

Platelet-Rich Plasma Gel Matrix (PRP-GM): Description of a New Technique.

Several musculoskeletal conditions are triggered by inflammatory processes that occur along with imbalances between anabolic and catabolic events. Platelet-rich plasma (PRP) is an autologous product derived from peripheral blood with inherent immunomodulatory and anabolic properties. The clinical efficacy of PRP has been evaluated in several musculoskeletal conditions, including osteoarthritis, tendinopathy, and osteonecrosis. When used in combination with hyaluronic acid (HA), a common treatment alternative, the regenerative properties of PRP are significantly enhanced and may provide additional benefits in terms of clinical outcomes. Recently, a new PRP-derived product has been reported in the literature and is being referred to as "plasma gel". Plasma gels are obtained by polymerizing plasmatic proteins, which form solid thermal aggregates cross-linked with fibrin networks. Plasma gels are considered to be a rich source of growth factors and provide chemotactic, migratory, and proliferative properties. Additionally, clot formation and the associated fibrinolytic reactions play an additional role in tissue repair. There are only a few scientific articles focusing on plasma gels. Historically, they have been utilized in the fields of aesthetics and dentistry. Given that the combination of three products (PRP, HA, and plasma gel) could enhance tissue repair and wound healing, in this technical note, we propose a novel regenerative approach, named "PRP-HA cellular gel matrix" (PRP-GM), in which leukocyte-rich PRP (LR-PRP) is mixed with a plasma gel (obtained by heating the plasma up) and HA in one syringe using a three-way stopcock. The final product contains a fibrin-albumin network entangled with HA's polymers, in which the cells and biomolecules derived from PRP are attached and released gradually as fibrinolytic reactions and hyaluronic acid degradation occur. The presence of leukocytes, especially monocytes and macrophages, promotes tissue regeneration, as type 2 macrophages (M2) possess an anti-inflammatory feature. In addition, HA promotes the viscosuplementation of the joint and induces an anti-inflammatory response, resulting in pain relief. This unique combination of biological molecules may contribute to the optimization of regenerative protocols suitable for the treatment of degenerative musculoskeletal diseases.

Application of Orthobiologics in Achilles Tendinopathy: A Review.

Orthobiologics are biological materials that are intended for the regeneration of bone, cartilage, and soft tissues. In this review, we discuss the application of orthobiologics in Achilles tendinopathy, more specifically. We explain the concepts and definitions of each orthobiologic and the literature regarding its use in tendon disorders. The biological potential of these materials can be harnessed and administered into injured tissues, particularly in areas where standard healing is disrupted, a typical feature of Achilles tendinopathy. These products contain a wide variety of cell populations, cytokines, and growth factors, which have been shown to modulate many other cells at local and distal sites in the body. Collectively, they can shift the state of escalated inflammation and degeneration to reestablish tissue homeostasis. The typical features of Achilles tendinopathy are failed healing responses, persistent inflammation, and predominant catabolic reactions. Therefore, the application of orthobiologic tools represents a viable solution, considering their demonstrated efficacy, safety, and relatively easy manipulation. Perhaps a synergistic approach regarding the combination of these orthobiologics may promote more significant clinical outcomes rather than individual application. Although numerous optimistic results have been registered in the literature, additional studies and clinical trials are still highly desired to further illuminate the clinical utility and efficacy of these therapeutic strategies in the management of tendinopathies.

Stromal Vascular Fraction for Knee Osteoarthritis - An Update.

Orthobiologics never cease to cause popularity within the medical science field, distinctly in regenerative medicine. Recently, adipose tissue has been an object of interest for many researchers and medical experts due to the fact that it represents a novel and potential cell source for tissue engineering and regenerative medicine purposes. Stromal vascular fraction (SVF), for instance, which is an adipose tissue-derivative, has generated optimistic results in many scenarios. Its biological potential can be harnessed and administered into injured tissues, particularly areas in which standard healing is disrupted. This is a typical feature of osteoarthritis (OA), a common degenerative joint disease which is outlined by persistent inflammation and destruction of surrounding tissues. SVF is known to carry a large amount of stem and progenitor cells, which are able to perform self-renewal, differentiation, and proliferation. Furthermore, they also secrete several cytokines and several growth factors, effectively sustaining immune modulatory effects and halting the escalated pro-inflammatory status of OA. Although SVF has shown interesting results throughout the medical community, additional research is still highly desirable in order to further elucidate its potential regarding musculoskeletal disorders, especially OA.

Application of Sygen® in Diabetic Peripheral Neuropathies-A Review of Biological Interactions.

This study investigates the role of Sygen® in diabetic peripheral neuropathy, a severe disease that affects the peripheral nervous system in diabetic individuals. This disorder often impacts the lower limbs, causing significant discomfort and, if left untreated, progresses into more serious conditions involving chronic ulcers and even amputation in many cases. Although there are management strategies available, peripheral neuropathies are difficult to treat as they often present multiple causes, especially due to metabolic dysfunction in diabetic individuals. Gangliosides, however, have long been studied and appreciated for their role in neurological diseases. The monosialotetrahexosylganglioside (GM1) ganglioside, popularly known as Sygen, provides beneficial effects such as enhanced neuritic sprouting, neurotrophism, neuroprotection, anti-apoptosis, and anti-excitotoxic activity, being particularly useful in the treatment of neurological complications that arise from diabetes. This product mimics the roles displayed by neurotrophins, improving neuronal function and immunomodulation by attenuating exacerbated inflammation in neurons. Furthermore, Sygen assists in axonal stabilization and keeps nodal and paranodal regions of myelin fibers organized. This maintains an adequate propagation of action potentials and restores standard peripheral nerve function. Given the multifactorial nature of this complicated disorder, medical practitioners must carefully screen the patient to avoid confusion and misdiagnosis. There are several studies analyzing the role of Sygen in neurological disorders. However, the medical literature still needs more robust investigations such as randomized clinical trials regarding the administration of this compound for diabetic peripheral neuropathies, specifically.

Ankle Osteoarthritis.

Osteoarthritis (OA) is characterized by a chronic, progressive and irreversible degradation of the joint surface associated with joint inflammation. The main etiology of ankle OA is post-traumatic and its prevalence is higher among young and obese people. Despite advances in the treatment of fractures around the ankle, the overall risk of developing post-traumatic ankle OA after 20 years is almost 40%, especially in Weber type B and C bimalleolar fractures and in fractures involving the posterior tibial border. In talus fractures, this prevalence approaches 100%, depending on the severity of the lesion and the time of follow-up. In this context, the current understanding of the molecular signaling pathways involved in senescence and chondrocyte apoptosis is fundamental. The treatment of ankle OA is staged and guided by the classification systems and local and patient conditions. The main problems are the limited ability to regenerate articular cartilage, low blood supply, and a shortage of progenitor stem cells. The present update summarizes recent scientific evidence of post-traumatic ankle OA with a major focus on changes of the synovia, cartilage and synovial fluid; as well as the epidemiology, pathophysiology, clinical implications, treatment options and potential targets for therapeutic agents.

Platelet-rich plasma vs bone marrow aspirate concentrate: An overview of mechanisms of action and orthobiologic synergistic effects.

The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disorders has increased considerably over the past decade. Currently, there are multiple alternatives available as suitable treatments; however, the use of autologous blood-derived products such as platelet-rich plasma (PRP), bone marrow aspirate (BMA) and BMA concentrate (BMAC), specifically, is expanding. Although many investigations attempted to demonstrate the effectiveness of these therapies, even with positive results, the literature lacks standardized protocols and overall accuracy in study designs, which leads to variance and difficulty in reproducibility of protocols. The efficacy of PRP for the treatment of cartilage, bone and muscle tissues is well known. Although BMAC has generated optimistic results for the same purposes, its applicability in clinical trials is still relatively recent when compared to PRP. Both products demonstrate the potential to set forth reparative processes, each in their own distinct mechanism. The combination of these biological products has been previously proposed, yet little is known about their synergism. Evidence indicates that growth factor, cytokine, and chemokine profiles seen in both PRP and BMAC vary but are likely to work synergistically to enhance musculoskeletal healing. BMAC products seem to work well without PRP; however, the addition of PRP to BMAC has been shown to act as a rich and natural source of culture medium for stem cells located either peripherally or in the bone marrow itself. Nevertheless, additional variables associated with the use of BMAC and PRP in orthopedics must be further evaluated in order to consolidate the efficacy of this therapeutic strategy.