Autologous Conditioned Serum in Knee Osteoarthritis: A Systematic Review of Current Clinical Evidence.

Knee osteoarthritis (OA) significantly impacts global health, causing pain, disability, and socioeconomic burden. Traditional treatments often provide only temporary relief and can have adverse effects. Autologous conditioned serum (ACS) therapy, which enriches a patient's own blood with growth factors and anti-inflammatory cytokines, has emerged as a promising approach to manage knee OA, potentially offering pain reduction, improved function, and tissue regeneration. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched databases such as PubMed, Web of Science, and Cochrane using terms like "Autologous Conditioned Serum" and "knee osteoarthritis." Clinical studies were selected based on their focus on ACS's efficacy in knee OA, assessing outcomes like pain relief, functional improvement, and adverse events. Eighteen studies met the inclusion criteria, including randomized controlled trials, observational studies, and comparative analyses. The review included a wide range of study designs and outcomes, highlighting ACS's efficacy in reducing pain and enhancing knee function as evidenced by various patient-reported outcome measures Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), Knee Society Clinical Rating Score (KSCRS) with a follow-up of up to 11 years (range: 2-11 years). Comparative studies showed ACS to be as effective or superior to conventional treatments such as platelet-rich plasma, steroids, and hyaluronic acid, especially in cases of moderate synovitis. Minimal adverse effects such as peri-injection pain, rigidity, synovitis, transient sensation of redness/heat, and numbness in the knee/leg/toes were reported, underscoring ACS's safety. Some studies suggested ACS might also have disease-modifying effects, contributing to tissue repair and integrity. ACS therapy offers a promising alternative for knee OA management, demonstrating potential benefits in symptom alleviation, functional improvement, and safety. Indications of disease-modifying properties further highlight its therapeutic value. However, the need for standardized formulations and treatment protocols, long-term studies, and mechanistic understanding remain. Future research should focus on addressing these gaps to fully elucidate ACS's role in the treatment landscape of knee OA.

Platelet Lysate and Osteoarthritis of the Knee: A Review of Current Clinical Evidence.

INTRODUCTION: Osteoarthritis (OA) of the knee affects millions of people with sizable socioeconomic burden. Conventional treatment modalities are prioritized, turning to surgical intervention only when they have failed. However, these traditional modalities have shortcomings, only aiming to reduce pain rather than targeting the underlying pathophysiology. Recently, the use of biologics, including autologous peripheral blood-derived orthobiologics (APBOs), has increased and demonstrated great promise for the management of knee OA. Platelet-rich plasma (PRP) is the most widely used APBO, but its efficacy is still uncertain, attributed to lack of standardized formulation protocols, characterization, and patient variables. To overcome the limitations posed by PRP, the use of other APBOs such as platelet lysate (PL) has been considered. This review summarizes the outcomes of clinical studies involving PL to manage OA of the knee. METHODS: Multiple databases (Scopus, Embase, PubMed, and Web of Science) were searched employing terms "platelet lysate" and "knee osteoarthritis" for articles published in the English language to August 15, 2024, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Only three clinical studies fulfilled our search and inclusion criteria. Intra-articular injection of three doses of PL injected every 3-4 weeks is safe and efficacious, resulting in statistically significant improvements in different patient-reported outcome measures at 6-12 months follow-up. CONCLUSION: The existing published peer-reviewed literature suggests that intra-articular injection of PL is safe and can decrease pain and increase function in patients with knee OA. Nonetheless, given the dearth of pertinent literature, more adequately powered, multicenter, prospective, non-randomized and randomized controlled studies with extended follow-up are needed to confirm the effectiveness of PL in knee OA. Further comparative studies to help clinicians in choosing the best APBO for knee OA treatment are also warranted.

Choosing ankle tourniquets in foot and ankle surgery: Beyond postoperative pain considerations.

This editorial critically explores the use of ankle vs thigh tourniquets in foot and ankle surgery based on a recent study that found no significant difference in postoperative pain between the two placement techniques. Despite these findings, we argue for the preferential use of ankle tourniquets, highlighting their potential benefits in reducing venous blood stasis and minimizing soft tissue injury. This approach underscores the importance of considering long-term patient outcomes and vascular health beyond immediate postoperative pain. By integrating study findings with broader clinical considerations, we hereby advocate for a nuanced approach to tourniquet use that prioritizes patient safety and long-term recovery in conjunction with immediate postoperative pain.

Osteoinductive potential of graphene and graphene oxide for bone tissue engineering: a comparative study.

BACKGROUND: Bone defects, especially critical-size bone defects, and their repair pose a treatment challenge. Osteoinductive scaffolds have gained importance given their potential in bone tissue engineering applications. METHODS: Polycaprolactone (PCL) scaffolds are used for their morphological, physical, cell-compatible and osteoinductive properties. The PCL scaffolds were prepared by electrospinning, and the surface was modified by layer-by-layer deposition using either graphene or graphene oxide. RESULTS: Graphene oxide-coated PCL (PCL-GO) scaffolds showed a trend for enhanced physical properties such as fibre diameter, wettability and mechanical properties, yield strength, and tensile strength, compared to graphene-modified PCL scaffolds (PCL-GP). However, the surface roughness of PCL-GP scaffolds showed a higher trend than PCL-GO scaffolds. In vitro studies showed that both scaffolds were cell-compatible. Graphene oxide on PCL scaffold showed a trend for enhanced osteogenic differentiation of human umbilical cord Wharton's jelly-derived Mesenchymal Stem Cells without any differentiation media than graphene on PCL scaffolds after 21 days. CONCLUSION: Graphene oxide showed a trend for higher mineralisation, but this trend is not statistically significant. Therefore, graphene and graphene oxide have the potential for bone regeneration and tissue engineering applications. Future in vivo studies and clinical trials are warranted to justify their ultimate clinical use.

Bone Marrow Aspirate Concentrate for Treatment of Primary Knee Osteoarthritis: A Prospective, Single-Center, Non-randomized Study with 2-Year Follow-Up.

Introduction: Knee osteoarthritis (OA) is a widespread, disabling condition with no intervention to fully restore cartilage or halt progression. Bone marrow aspirate concentrate (BMAC), an autologous product from bone marrow aspiration, has shown promise as a regenerative therapy due to its cell composition and chondrogenic effects. Our study aims to assess the functional outcomes, including pain, function, satisfaction, and complications post-BMAC injection in knee OA patients. Materials and Methods: In this prospective, single-center study, 63 patients with grade II-III knee OA (Kellgren-Lawrence (K-L) scale) unresponsive to conservative management underwent BMAC injection. The procedure involved bone marrow aspiration from the anterior iliac crest, processing to obtain a concentrate, followed by intra-articular injection. Patients were followed for 24 months, assessing outcomes using the Visual Analog Scale (VAS), International Knee Documentation Committee (IKDC) score, and MOCART 2.0 score. Results: The cohort, with a slight female predominance and predominantly aged 41-50 years, majorly comprised K-L grade III OA patients. BMAC treatment resulted in significant improvements in VAS pain scores, IKDC functional scores, and MOCART 2.0 scores over the 24-month follow-up. Conclusion: BMAC injection provides significant improvement in both pain and functional outcomes at mid-term follow-up in patients with mild-to-moderate OA of the knee. Further high-quality, adequately powered, multi-center, prospective, double-blinded, randomized controlled trials with longer follow-up are necessary to justify the routine clinical use of BMAC for treatment of patients suffering with knee OA.

Safety and Efficacy of Bone-Marrow Aspirate Concentrate in Hip Osteoarthritis: A Systematic Review of Current Clinical Evidence.

Introduction: Hip osteoarthritis (OA) is one of the leading causes of disability and morbidity worldwide. It is estimated to affect 9.2% individuals globally with age over 45 years. Conventional treatment modalities have limitations and side-effects. To overcome these limitations, over the last decade, there has been an increased interest in the use of orthobiologics derived from autologous sources including platelet-rich plasma (PRP), bone-marrow aspirate concentrate (BMAC) and adipose tissue derived formulations. This review qualitatively presents the in-vitro, pre-clinical, clinical and on-going clinical studies exploring the safety and efficacy of BMAC for management of hip OA. Materials and methods: The electronic database search was done through PubMed, Embase, Web of Science, Scopus, ProQuest and Google Scholar till February 2024. The search terms used were "osteoarthritis" OR "hip osteoarthritis" OR "orthobiologics" OR "efficacy or use of orthobiologic treatment" OR "bone-marrow concentrate" OR "bone-marrow aspirate concentrate", AND "BMAC". The inclusion criteria were clinical studies of any level of evidence written in the English language, published till February 2024, evaluating the safety and efficacy of intra-articular administration of BMAC for the management of hip OA. Results: A total of 5 studies were included in this review for qualitative data synthesis. The total number of patients who participated in the study was 182, ranging from 4 to 112 in a single study. No adverse events were reported throughout the duration of the study. In addition, intra-articular administration of BMAC led to reduced pain, and improved function and overall quality of life (QoL). Conclusion: The results from this review demonstrated that administration of BMAC is safe and potentially efficacious in terms of reducing pain, improving function and overall QoL of patients with hip OA in short- and mid-term average follow-up based on the included studies. Nonetheless, more adequately powered, multi-center, prospective, double-blind, non-randomized and randomized controlled trials with long-term follow-up are warranted to establish long-term safety and efficacy of BMAC for management of hip OA and justify its routine clinical use.

Growth Factor Concentrate (GFC) for the Management of Osteoarthritis of the Knee: A Systematic Review.

Introduction: The knee is the most commonly affected joint in osteoarthritis (OA), affecting millions of people worldwide. Knee OA significantly impacts the activities of daily living (ADL) along with affecting overall quality of life of patients (QoL), thereby leading to substantial socio-economic burden. Conservative therapies are prioritized, resorting to surgery only when needed. However, these traditional approaches have limitations. Regenerative medicine, involving the use of orthobiologics, including autologous peripheral blood-derived orthobiologics such as growth factor concentrate (GFC), has evolved and shown potential for managing knee OA. The primary goal of this review is to summarize the results of in vitro, preclinical and clinical studies involving GFC for the management of knee OA. Methods: Multiple databases (PubMed, Scopus, Google Scholar, Web of Science and Embase) were searched applying terms for the intervention 'GFC' and treatment 'knee OA' for the studies published in the English language to March 10, 2024. Results: Only three clinical studies met our pre-defined criteria and were included in this review. Conclusion: Intra-articular administration of GFC is safe and potentially efficacious to manage OA of the knee. More, adequately powered, multi-center, prospective, RCTs are warranted to demonstrate the long-term effectiveness of GFC in patients suffering from mild-to-moderate knee OA and to justify its routine clinical use. Further studies evaluating the efficacy of GFC compared to other orthobiologics are also required to allow physicians/surgeons to choose the optimal orthobiologic for the treatment of OA of the knee.

Efficacy of stromal vascular fraction for knee osteoarthritis: A prospective, single-centre, non-randomized study with 2 years follow-up.

BACKGROUND: Current osteoarthritis (OA) treatments focus on symptom relief without addressing the underlying disease process. In regenerative medicine, current treatments have limitations. In regenerative medicine, more research is needed for intra-articular stromal vascular fraction (SVF) injections in OA, including dosage optimization, long-term efficacy, safety, comparisons with other treatments, and mechanism exploration. AIM: To compare the efficacy of intra-articular SVF with corticosteroid (ICS) injections in patients with primary knee OA. METHODS: The study included 50 patients with Kellgren-Lawrence grades II and III OA. Patients were randomly assigned (1:1) to receive either a single intra-articular SVF injection (group A) or a single intra-articular ICS (triamcinolone) (group B) injection. Patients were followed up at 1, 3, 6, 12, and 24 months. Visual analog score (VAS) and International Knee Documentation Committee (IKDC) scores were administered before the procedure and at all follow-ups. The safety of SVF in terms of adverse and severe adverse events was recorded. Statistical analysis was performed with SPSS Version 26.0, IBM Corp, Chicago, IL, United States. RESULTS: Both groups had similar demographics and baseline clinical characteristics. Follow-up showed minor patient loss, resulting in 23 and 24 in groups A and B respectively. Group A experienced a notable reduction in pain, with VAS scores decreasing from 7.7 to 2.4 over 24 months, compared to a minor reduction from 7.8 to 6.2 in Group B. This difference in pain reduction in group A was statistically significant from the third month onwards. Additionally, Group A showed significant improvements in knee functionality, with IKDC scores rising from 33.4 to 83.10, whereas Group B saw a modest increase from 36.7 to 45.16. The improvement in Group A was statistically significant from 6 months and maintained through 24 months. CONCLUSION: Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA. More adequately powered, multi-center, double-blinded, randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.

Autologous peripheral blood-derived orthobiologics: Different types and their effectiveness in managing knee osteoarthritis.

Knees are the most commonly impacted weight-bearing joints in osteoarthritis (OA), affecting millions of people worldwide. With increasing life spans and obesity rates, the incidence of knee OA will further increase, leading to a significant increase in the economic burden. Conventional treatment modalities utilized to manage knee OA have limitations. Over the last decade, the role of various autologous peripheral blood-derived orthobiologics (APBOs) for the treatment of knee OA has been extensively investigated. This editorial provided an overview and focused on defining and shedding light on the current state of evidence based on the most recent published clinical studies concerning the use of APBO for the management of knee OA. While numerous studies have demonstrated promising results for these preparations, a notable gap exists in the comparative analysis of these diverse formulations. This absence of head-to-head studies poses a considerable challenge for physicians/surgeons in determining the optimal preparation for managing knee OA and achieving sustained long-term results. Thus, more adequately powered, multicenter, prospective, double-blind, randomized controlled trials with longer follow-ups are needed to establish the long-term efficacy and to aid physicians/surgeons in determining the optimal APBO for the management of knee OA.

H-Wave® Device Stimulation for Chronic Neck Pain: A Patient-Reported Outcome Measures (PROMs) Study.

INTRODUCTION: Chronic neck pain (cNP) is one of the leading causes of disability worldwide, often being refractory to conventional forms of treatment. Various forms of electrical stimulation have been proposed to decrease pain and improve function. Patient-reported outcome measures (PROMs) for treatment of cNP have rarely been published. METHODS: An independent retrospective statistical analysis of PROMs data for users of H-Wave® device stimulation (HWDS), prospectively collected by the device manufacturer over a 4-year period, was conducted. Final surveys for 34,192 pain management patients were filtered for pain chronicity limited to 3-24 months and device use of 22-365 days, resulting in 11,503 patients with "all diagnoses"; this number was further reduced to 1482 patients with cNP, sprain, or strain. RESULTS: Neck pain was reduced by 3.13 points (0-10 pain scale), with significant (≥ 20%) relief in 86.6%. Function/activities of daily living (ADL) improved in 96.19%, while improved work performance was reported in 84.76%. Medication use decreased or stopped in 65.42% and sleep improved in 60.39%. Over 95% reported having expectations met or exceeded, service satisfaction, and confidence in device use, while no adverse events were reported. Subgroup analyses found positive benefit associations with longer duration of device use. CONCLUSION: Near-equivalent outcomes were self-reported by cNP HWDS patients as for (previously published) chronic low back pain (cLBP) patients. HWDS provided effective and safe cNP relief, improvements in function and ADL, along with additional benefits including decreased medication use, better sleep, and improved work performance.

Exosomes for the Management of Low Back Pain: A Review of Current Clinical Evidence.

Low back pain affects millions of people, creating an enormous financial burden on the global healthcare system. Traditional treatment modalities are short-lived and have shortcomings. Recently, orthobiologics, including extracellular vesicles or exosomes derived from mesenchymal stem cells, have markedly increased for managing musculoskeletal conditions. Here, the primary aim is to review the outcomes of clinical studies using extracellular vesicles or exosomes for treating low back pain. Numerous databases (Scopus, PubMed, Web of Science, Embase, and Google Scholar) were searched using terms for the intervention 'exosomes' and the treatment 'low back pain' for studies published in English to March 18, 2024. Articles utilizing exosomes for the management of low back pain were included. Articles not utilizing exosomes, not explicitly stating the presence of exosomes in their formulation, or not targeting low back pain were excluded. Two articles that met our pre-defined criteria were included in this review. The results showed that administering extracellular vesicles or exosomes is safe and potentially effective in patients suffering from low back pain. Yet, more sufficiently powered, multi-center, prospective, randomized, and non-randomized trials with longer follow-up are essential to assess the long-term safety and efficacy of extracellular vesicles or exosomes derived from various sources and to support its routine clinical use for managing low back pain.

Addressing cortex dysregulation in youth through brain health check coaching and prophylactic brain development.

The Carter Center has estimated that the addiction crisis in the United States (US), if continues to worsen at the same rate, may cost the country approximately 16 trillion dollars by 2030. In recent years, the well-being of youth has been compromised by not only the coronavirus disease 2019 pandemic but also the alarming global opioid crisis, particularly in the US. Each year, deadly opioid drugs claim hundreds of thousands of lives, contributing to an ever-rising death toll. In addition, maternal usage of opioids and other drugs during pregnancy could compromise the neurodevelopment of children. A high rate of DNA polymorphic antecedents compounds the occurrence of epigenetic insults involving methylation of specific essential genes related to normal brain function. These genetic antecedent insults affect healthy DNA and mRNA transcription, leading to a loss of proteins required for normal brain development and function in youth. Myelination in the frontal cortex, a process known to extend until the late 20s, delays the development of proficient executive function and decision-making abilities. Understanding this delay in brain development, along with the presence of potential high-risk antecedent polymorphic variants or alleles and generational epigenetics, provides a clear rationale for embracing the Brain Research Commission's suggestion to mimic fitness programs with an adaptable brain health check (BHC). Implementing the BHC within the educational systems in the US and other countries could serve as an effective initiative for proactive therapies aimed at reducing juvenile mental health problems and eventually criminal activities, addiction, and other behaviors associated with reward deficiency syndrome.

Identification of stress-induced epigenetic methylation onto dopamine D2 gene and neurological and behavioral consequences.

The D2 dopamine receptor (DRD2) gene has garnered substantial attention as one of the most extensively studied genes across various neuropsychiatric disorders. Since its initial association with severe alcoholism in 1990, particularly through the identification of the DRD2 Taq A1 allele, numerous international investigations have been conducted to elucidate its role in different conditions. As of February 22, 2024, there are 5485 articles focusing on the DRD2 gene listed in PUBMED. There have been 120 meta-analyses with mixed results. In our opinion, the primary cause of negative reports regarding the association of various DRD2 gene polymorphisms is the inadequate screening of controls, not adequately eliminating many hidden reward deficiency syndrome behaviors. Moreover, pleiotropic effects of DRD2 variants have been identified in neuropsychologic, neurophysiologic, stress response, social stress defeat, maternal deprivation, and gambling disorder, with epigenetic DNA methylation and histone post-translational negative methylation identified as discussed in this article. There are 70 articles listed in PUBMED for DNA methylation and 20 articles listed for histone methylation as of October 19, 2022. For this commentary, we did not denote DNA and/or histone methylation; instead, we provided a brief summary based on behavioral effects. Based on the fact that Blum and Noble characterized the DRD2 Taq A1 allele as a generalized reward gene and not necessarily specific alcoholism, it now behooves the field to find ways to either use effector moieties to edit the neuroepigenetic insults or possibly harness the idea of potentially removing negative mRNA-reduced expression by inducing "dopamine homeostasis."

Effect of weight-adjusted antimicrobial antibiotic prophylaxis on postoperative dosage and surgical site infection incidence in total joint arthroplasty.

Surgical site infections (SSI) following total joint arthroplasty pose a significant concern for both providers and patients across the globe. Currently, administration of antimicrobial antibiotic prophylaxis is used throughout the world to reduce the incidence of SSI. However, the correct dosage and frequency of administration remains debatable. In this editorial, we emphasized the determination of the effect of administration of weight-adjusted antimicrobial antibiotic prophylaxis regime on the incidence of SSI and postoperative dosage reduction compared to the conventionally used regime during total joint arthroplasty. The results demonstrated similar efficacy between both regimes with respect to the incidence of SSI. In addition, weight-adjustment led to reduced postoperative dosage and has the potential to reduce chances of achieving lower therapeutic concentration, drug resistance, drug toxicity, and costs.

Optimization of Polycaprolactone and Type I Collagen Scaffold for Tendon Tissue Regeneration.

Introduction Collagen synthesis is vital for restoring musculoskeletal tissues, particularly in tendon and ligamentous structures. Tissue engineering utilizes scaffolds for cell adhesion and differentiation. Although synthetic scaffolds offer initial strength, their long-term stability is surpassed by biological scaffolds. Combining polycaprolactone (PCL) toughness with collagen in scaffold design, this study refines fabrication via electrospinning, aiming to deliver enduring biomimetic matrices for widespread applications in musculoskeletal repair. Methods Electrospinning employed four solutions with varied collagen and PCL concentrations, dissolved in chloroform, methanol, and hexafluoro-2-propanol. Solutions were combined to yield 60 mg/mL concentrations with different collagen/PCL ratios. Electrospinning at 12-14kV voltage produced scaffolds, followed by vacuum-drying. Collagen coating was applied to PCL and 15% collagen/PCL scaffolds using a 0.1% collagen solution. SEM characterized fiber morphology, tensile testing was conducted to determine the mechanical properties of the scaffold, and Fourier-transform infrared (FTIR) spectroscopy analyzed scaffold composition. Atomic force microscopy (AFM) analyzed the stiffness properties of individual fibers, and a finite element model was developed to predict the mechanical properties. Cell culture involved seeding human bone marrow mesenchymal stem cells onto scaffolds, which were assessed through Alamar Blue assay and confocal imaging. Results Various scaffolds (100% PCL, PCL-15% collagen, PCL-25% collagen, PCL-35% collagen) were fabricated to emulate the extracellular matrix, revealing collagen's impact on fiber diameter reduction with increasing concentration. Tensile testing highlighted collagen's initial enhancement of mechanical strength, followed by a decline beyond PCL-15% collagen. FTIR spectroscopy detected potential hydrogen bonding between collagen and PCL. A finite element model predicted scaffold response to external forces which was validated by the tensile test data. Cell viability and proliferation assays demonstrated successful plating on all scaffolds, with optimal proliferation observed in PCL-25% collagen. Confocal imaging confirmed stem cell integration into the three-dimensional material. Collagen coating preserved nanofiber morphology, with no significant changes in diameter. Coating of collagen significantly altered the tensile strength of the scaffolds at the macro scale. AFM highlighted stiffness differences between PCL and collagen-coated PCL mats at the single fiber scale. The coating process did not significantly enhance initial cell attachment but promoted increased proliferation on collagen-coated PCL scaffolds. Conclusion The study reveals collagen-induced mechanical and morphological alterations, influencing fiber alignment, diameter, and chemical composition while emphasizing scaffolds' vital role in providing a controlled niche for stem cell proliferation and differentiation. The optimization of each of these scaffold characteristics and subsequent finite element modeling can lead to highly repeatable and ideal scaffold properties for stem cell integration and proliferation.

Management of rotator cuff injuries using allogenic platelet-rich plasma.

Rotator cuff injuries are a major cause of shoulder pain, affecting the quality of life and producing a significant burden on healthcare systems. Conservative management modalities are prioritized, resorting to surgery only when required. The field of regenerative medicine involving the use of biologics, such as platelet-rich plasma (PRP), has evolved and shown potential for managing rotator cuff injuries. Nonetheless, limitations including subpar outcomes have led clinicians to question the efficacy of autologous PRP. To circumvent this, the possibility of utilizing a standardized and well-characterized allogenic PRP for RCI has been explored. In this manuscript, we qualitatively present the evidence from in vitro, pre-clinical, clinical and ongoing studies investigating the applications of allogenic PRP in the context of rotator cuff disorders. Administration of allogenic PRP is safe and potentially efficacious to manage rotator cuff injuries, though more adequately powered randomized controlled trials with longer follow-ups are warranted to further establish the efficacy of allogenic PRP and justify its routine clinical use.