C. Thomas Vangsness

Purpose: To review the current literature to determine which injection technique and needle portal placement provide the greatest accuracy for intra‐articular access to the knee. Methods: This study followed Preferred Reporting Items and Systematic Reviews and Meta‐Analyses guidelines. A comprehensive literature search was conducted in March 2020 and repeated in May 2020 using electronic databases PubMed, MEDLINE, and the Cochrane Library. Data on the accuracy of intra‐articular knee injection (successful injections/total number of injections) were collected. Only Level I studies were included. Study design, demographic variables, needle sizes, and method of validating accuracy were recorded. The Jadad score was used to assess methodologic quality, and a risk‐of‐bias assessment was performed. Results: A total of 12 Level I human studies (1431 patients, 1315 knees) were included in this review. Seven of the studies did a direct comparison between ultrasound‐guided and blind knee injections. Ultrasound‐guided injections were more accurate compared with blinded knee injections in every study. The most accurate anatomical approach was an isometric quadricep contraction method with the superolateral approach. Conclusions: This study showed that ultrasound‐guided knee injections were more accurate across every anatomical needle injection site compared with blind injections. Injections made by a blind/anatomically guided method had inconsistent accuracy rates that seemed highly dependent on the portal of entry. Level of Evidence: Level I, s ystematic review of Level I studies.

Purpose: To assess the efficacy of platelet‐rich plasma (PRP) for lateral epicondylitis and evaluate its impact on pain and functional outcomes. Methods: This study followed Preferred Reporting Items and Systematic Reviews and Meta‐Analyses guidelines. A comprehensive literature search was conducted in September 2019 and repeated in April 2020 using electronic databases PubMed, MEDLINE, and the Cochrane Library. Baseline and 3‐, 6‐, and 12‐month data were extracted for visual analog scale (VAS), Disabilities of the Arm, Shoulder, and Hand (DASH), and modified Mayo Clinic performance index for the elbow (MAYO) scores. Only level 1 studies with patients who had not undergone surgery were included. Outcomes data, study design, demographic variables, PRP formulation, and comparator treatments were recorded. Statistical analyses of pooled weighted mean differences (WMDs) were performed and compared with estimated minimal clinically important difference (MCID) values. The Coleman Methodology Score (CMS) was used to assess methodological quality, and the Cochrane risk‐of‐bias assessment was performed. Results: This review included 16 level I studies, 9 of which (581 total patients, 281 receiving single injections of PRP) were quantitatively analyzed. The average age was 41.5 years, 56.8% of patients were female, and mean follow‐up was 7.5 months. The mean CMS was 78.94 ± 12.74 (range 59 to 97), and 5 of 16 studies were at low risk for bias. Patients who received PRP had significantly improved VAS scores at 3 months (WMD –0.85; 95% confidence interval [CI] –1.03, –0.66; P < .01) and 6 months (WMD –0.74; 95% CI –0.98, –0.50; P < .01) compared with those who received autologous whole blood, though MAYO scores were statistically equivalent. Comparing PRP to corticosteroids, VAS and DASH scores were not significantly different at 3 months, although PRP was superior at 6 months for VAS (WMD –1.70; 95% CI –2.65, –0.75; P < .01) and DASH (WMD –6.23; 95% CI –10.78, –1.69; P < .01). Most differences in VAS and DASH scores exceeded the 5% absolute difference estimate for their respective MCIDs but fell short of the 10% estimate. Conclusion: Considering the small number of comparable studies, lack of quantification of specific PRP content, considerable heterogeneity between randomized control trials, and most effect sizes being equivocal within the framework of 2 estimated MCID values, the authors can neither scientifically support nor discourage the usage of PRP for lateral epicondylitis despite finding statistically significant improvements in pain and functional outcomes. Level of Evidence: I, prognostic.

Accurately measuring the length and diameter of the hamstring tendon autograft preoperatively is important for planning anterior cruciate ligament (ACL) reconstructive surgery. The purpose of this study was to assess the reliability of three-dimensional computed tomography (3D CT) scanning technique to produce the actual measurement of the gracilis and semitendinosus (GT and ST, respectively) tendon grafts' length and diameter for surgery. Ninety patients were scheduled for ACL reconstruction with hamstring autograft. Before the surgery, patients were examined under the multidetector row CT scanner and the ST and GT tendons were qualitatively measured by a volume-rendering technique. The length of ST and GT was measured with 3D CT compared with the length of the harvested ST and GT. The cross-sectional area (CSA) of ST and GT measured with 3D CT compared with the ST and GT graft diameter. Tendon size measured preoperatively and during surgery were statistically compared and correlated. The GT tendons length and cross-sectional area measured during surgery was both shorter and smaller compared with the ST tendon. GT and ST tendon length were correlated to patients' body index such as the height and weight (p < 0.05). However, the correlation levels were low to medium (r = 0.23–0.49). There was strong correlation between the lengths of GT (r = 0.76; p < 0.001) and ST (r = 0.87; p < 0.001) measured with the 3D CT and tendon length at surgery. There was a moderate correlation between graft diameter measured at surgery and 3D CT cross-sectional area (r = 0.31; p < 0.05). A multidetector row CT scanner can determine the ST and GT tendons' length and diameter. These measurements can be used for preoperative planning to help determine the surgical method and counsel patients on appropriate graft choices prior to surgery.

Objective: Alteration of the cellular microenvironment may influence the intra- and intercellular communication and contribute to cartilage injury and repair. The purpose of this study was to investigate how matrix elasticity/stiffness affects chondrogenic activities, including cell survival, phenotypic expression, and the release of both pro- and anti-inflammatory cytokines. Design: Human articular chondrocytes (HACs) cultured on traditional 2-dimensional (2D) plastic surfaces were compared with those cultured within 3D hydrogel matrices of varying stiffness. Chondrogenic proliferation, differentiation, and the expression of pro- and anti-inflammatory cytokines were evaluated. Both interleukin-1-beta (IL-1β) and human synovial fluid–derived cells (hSFCs) were introduced to study the effects of matrix stiffness on chondrocyte response. Results: Cells demonstrated the most robust chondrogenic differentiation and secreted the least pro-inflammatory cytokines when the matrix stiffness was close to their native microenvironment. The IL-1β effects were attenuated when HACs were co-cultured with hSFCs. Conclusion: Modifying the matrix stiffness to mimic the native cartilage microenvironment not only optimized chondrogenic expression but also was essential for the regulation of physiological homeostasis. This study proposed a new toolkit to study cell-molecule, cell-cell, and cell-matrix influence on cartilage physiology.

The United States Food and Drug Administration (FDA) is responsible for protecting and promoting public health through rules and regulations. Over the past few years, the field of regenerative medicine and cell therapy have garnered significant interest, and this evolving new biology is changing fast and challenging regulatory bodies. The FDA has published a series of guidance documents outlining steps to protect consumers against potentially dangerous and unproven treatments. The agency has offered a grace period for “stem cell clinics” until November 2020 to come into compliance by obtaining Investigational New Drug applications and working to secure premarket approval of their products. With the documentation of hundreds of “stem cell clinics,” the FDA needs to enforce the adherence to their outlined standards to protect patients. The aim of this review was to provide an overview of these FDA regulations and some current issues within the industry. The purpose is to educate and inform the musculoskeletal community about the current government regulations of this new expanding biology. Level of Evidence: Level V, expert opinion.

Mesenchymal stem cells (MSCs) are adult stem cells that have the ability to self-renew and differentiate into several cell lineages including adipocytes, chondrocytes, tenocytes, bones, and myoblasts. These properties make the cell a promising candidate for regenerative medicine applications, especially when dealing with sports injuries in the knee. MSCs can be isolated from almost every type of adult tissue. However, most of the current research focuses on MSCs derived from bone marrow, adipose, and placenta derived products. Synovial fluid-derived MSCs (SF-MSCs) are relatively overlooked but have demonstrated promising therapeutic properties including possessing higher chondrogenic proliferation capabilities than other types of MSCs. Interestingly, SF-MSC population has shown to increase exponentially in patients with joint injury or disease, pointing to a potential use as a biomarker or as a treatment of some orthopaedic disorders. In this review, we go over the current literature on synovial fluid-derived MSCs including the characterization, the animal studies, and discuss future perspectives.

Exosomes are extracellular vesicles (EVs) released from cells that are a part of many biological and pathological processes, especially in intercellular communication. These vesicles are involved cell signaling, influence tissue and immune response, and serve as biomarkers for diseases. Most interesting are the exosomes that are released from mesenchymal stem cells (MSCs) for inflammation in joint diseases. Preliminary studies have demonstrated the advantages of using EVs rather than MSCs for cell free therapy. Research on exosomes have shown promising results as biomarkers for tracking the pathogenesis and prognosis of inflammatory arthritis. Therapeutically, animal studies have demonstrated immunosuppression, reversing inflammation, increasing chondrocyte proliferation, and drug delivery properties. The field of exosomes continues to develop and more basic science and clinical studies with safety and efficacy studies are needed.