Antonio Marmotti

Tendinopathy is a prevalent musculoskeletal condition characterised by chronic inflammatory and degenerative changes. Pulsed electromagnetic fields (PEMFs) represent a promising biophysical therapeutic modality, yet their effects across different inflammatory states of tendinopathy remain poorly characterised. To evaluate PEMF biological effects on human tenocytes, three in vitro models differing in IL-1β dose and duration were tested: acute low-dose (0.1 ng/mL, 96 h), acute high-dose (1 ng/mL, 96 h), and prolonged (0.1 ng/mL, 9 days). At the transcriptional level, PEMFs significantly reduced IL-6 and IL-8 mRNA overexpression in the acute low-dose model and CCL2 upregulation in the prolonged model. At the secretome level, PEMFs reduced GM-CSF and IL-8 secretion in the acute high-dose model, and suppressed CCL2 and CCL5 protein secretion in the prolonged model. MMP activity was not modulated by PEMFs in any condition. PEMFs consistently increased tenocyte proliferation across both the acute models. Finally, in wound healing assays, non-inflamed tenocytes exposed to PEMFs showed significantly enhanced wound closure compared to IL-1β-treated cells across all models; in the acute low-dose model, PEMFs also significantly improved wound closure in IL-1β-treated cells at an early timepoint, whereas no such effect was observed in cells exposed to high-dose or prolonged inflammation. PEMFs exert context-dependent effects, promoting healing primarily during acute or mild inflammation. These findings suggest that the inflammatory stage of tenocytes may influence PEMF responsiveness in vitro, highlighting the importance of considering this variable in the design of future clinical studies evaluating PEMF therapy for tendinopathy.

Aims: Hamstring tendons are commonly used autografts for anterior cruciate ligament (ACL) reconstruction. They represent an optimal source for in vitro testing of new approaches that may improve tendon regeneration and, likely, ligamentization after ACL reconstruction. We assessed ex vivo, in a 3D explant culture, the anabolic effect of pulsed electromagnetic fields (PEMF) on hamstring tendons in an experimental setting as close as possible to that of common clinical applications, suggesting a potential new therapeutic strategy to improving tendon remodelling. Methods: We exposed tendon explants from nine donors to PEMF for 21 days, eight hours/day, with an intensity similar to that used in clinical practice, and evaluated specific gene expression by immunofluorescence and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses. Results: Increased expression of tendon-related markers (scleraxis, collagen types I and VI) and important players of tenogenic differentiation (c-Fos and mammalian target of rapamycin) was evidenced by immunofluorescence analysis upon PEMF exposure and confirmed by qRT-PCR analysis. Conclusion: Our results demonstrate that PEMF enhances tendon differentiation, which suggests that PEMF exposure could have clinical relevance as a new non-invasive adjuvant treatment for improving the early phases of hamstring autograft remodelling after ACL reconstruction, as well as possibly for hastening the repair of injured tendons. Cite this article: Bone Joint Res 2026;15(2):167–178.

Background/Objectives: The aim of the study was to investigate the clinical, functional, and radiographic results of patients affected by three- or four-part proximal humeral fractures treated with reverse total shoulder arthroplasty, to investigate whether a prosthetic stem nonspecifically designed for fractures (i.e., the Bigliani-Flatow stem) promotes tuberosities’ healing, and to evaluate the impact of tuberosity fixation and healing on the outcomes. Methods: Patients’ data such as gender, age, side and dominancy, comorbidities, complications during or after surgery, and time lapse between trauma and surgery were prospectively collected. The type of fixation of the stem, the thickness and type of liner, and whether the tuberosities were fixed or not were also recorded. The Constant score weighted on the contralateral limb, QuickDASH, Oxford Shoulder Score, and Subjective Shoulder Value were collected. Tuberosities’ healing was assessed with X-rays (anteroposterior, Grashey, and axillary views). Results: Overall, 34 patients were included, with an average follow-up of 42 months. Tuberosities were reinserted in 24 cases and their healing rate was 83%. The mean values were the following: a Constant score of 64, Oxford Shoulder Score of 39, Subjective Shoulder Value of 71, and QuickDASH score of 27. There were no significant differences in the scores or range of motion between patients with tuberosities healed, reabsorbed, or not reattached. There was a better external rotation in the group with healed tuberosities and a longer duration of surgery to reattach tuberosities. Conclusions: The treatment of proximal humerus fractures with the Bigliani-Flatow stem is associated with good clinical and functional results. The healing rate of the tuberosities was high and comparable, if not even better, than the mean rates reported for the stems dedicated to fractures of the proximal humerus and was, therefore, also appropriate for this indication.

Coronal shear fractures of the distal humerus are rare, frequently comminuted, and are without consensus for treatment. The aim of this paper is to review the current concepts on the diagnosis, classification, treatment options, surgical approaches, and complications of capitellar and trochlear fractures. Computed Tomography (CT) scans, along with the Dubberley classification, are extremely helpful in the decision-making process. Most of the fractures necessitate open reduction and internal fixation, although elbow arthroplasty is an option for comminuted fractures in the elderly low-demand patient. Stiffness is the most common complication after fixation, although reoperation is infrequent.

Background: The treatment of a displaced proximal humeral fracture is still a matter of controversy. Minimally invasive techniques are considered promising options. The purpose of this study was to report outcomes at medium to long-term follow-up after surgical treatment with pins stabilized with an external fixator. Methods: A total of 235 patients (average age, 64 years [95% confidence interval (CI), 62 to 65 years]) were treated with closed or open reduction and fixation with pins stabilized by an external fixator specifically designed for proximal humeral fractures. The pins were inserted using a “pins-crossing-fracture” or a “pins-bridging-fracture” technique. One hundred and eighty-eight patients had a minimum radiographic and clinical follow-up of 2 years. Outcomes were assessed using the Oxford Shoulder Score (OSS), the subjective shoulder value (SSV), a visual analog scale (VAS) for pain, and, for 155 patients, the Constant score. Results: Eighty-one (43%) of the 188 patients had a 2-part fracture, 60 (32%) had a 3-part fracture, and 47 (25%) had a 4-part fracture. The reduction was performed with percutaneous maneuvers in 120 shoulders or a deltopectoral approach, in 68. The external fixator was applied using a “pins-crossing-fracture” technique in 133 shoulders and using a “pins-bridging-fracture” technique in 55. At last follow-up, mean clinical scores were as follows: OSS, 42.6 (95% CI, 42 to 44); SSV, 85.5 (95% CI, 83 to 88); and VAS for pain, 1 (95% CI, 0.7 to 1.2). The complication rate at 3 months was 16% (37 of 235). The most frequent complication was pin-track infection (19 of 235, 8%). A total of 50 patients had ≥1 complication (50 of 188, 27%) and 6 (3%) underwent revision surgery. More complications were observed with the “pins-crossing-fracture” technique. Conclusions: In our experience, the use of the external fixator has been a valuable option in the treatment of proximal humeral fractures. The complication and revision rates were acceptable. Most of the complications encountered were manageable without revision surgery. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

MiRNAs are emerging as key regulators of complex biological systems in several developmental processes. qRT-PCR is a powerful tool to quantitatively assess the profiles and modulation of miRNA expression. In the emerging field of cartilage maturation studies, from precursor to hypertrophic chondrocytes, few data about miRNA regulation are available, and no consensus on the best reference gene (RG) has been reached. This is a crucial pitfall since reliable outcomes depend on proper data normalization. The aim of this work was to identify reliable and stable miRNA RGs, basing the analysis on available high throughput qRT-PCR miRNA data (from the NCBI Gene Expression Omnibus database, GSE49152) obtained from human embryonic cartilage tissues enriched in the precursor, differentiated, and hypertrophic chondrocytes. Four normalization approaches were used, and the stability was quantified by combining BestKeeper, delta-Ct, geNorm, and NormFinder statistical tools. An integrated approach allowed to identify miR-26a-5p as the most stable RG and miR-212-3p as the worst one. RNU44, used in original dataset analysis, performed as second best RG. Applications of different normalization strategies significantly impacted the profiles and modulation of miRNA expression. Herein presented results point out the crucial need of a consensus on data normalization studies aimed at dissecting miRNA role in human cartilage development, to avoid the postulation of unreliable biological conclusions.

[This corrects the article DOI: 10.1155/2018/9048237.].

Total hip arthroplasty (THA) represents one of the commonest surgical procedures in the orthopedic field. Osteointegration of the implant with native bone is essential for an optimal result; thus, the quality of the patient’s bone surrounding the implant (i.e., the bone stock) is crucial. However, in some cases, the bone stock is insufficient and needs to be improved with autologous grafts rich in multipotent cells (i.e., from the iliac crest, from the head of the femur, or from the subchondral bone harvested from the acetabulum) or allogenic frozen bone. It is not known if the harvesting site may influence the osteogenic potential of these cells. Thus, our aim was to characterize and compare multipotent cells collected from the bone marrow, acetabular subchondral bone, and trabecular bone on the femoral head with a focus on osteogenic differentiation. The cells from three sources had a fibroblast-like phenotype and expressed surface antigens CD73, CD90, and CD105 and are negative to CD11b, CD34, and CD45. Although all these cells could be induced to differentiate into osteoblasts, chondrocytes, and adipocytes, they displayed different differentiation potentials. In osteogenic differentiation condition, the cells from the acetabulum had the lowest accumulation of calcium deposit while the cells originated from the bone marrow and femur created a considerably increased amount of the deposit. These findings were confirmed by quantitative polymerase chain reaction (qPCR). In chondrogenic and adipogenic conditions, bone marrow cells possessed a predominant differential capacity compared with the others, illustrated by high collagen type II expression together with a cartilage-like lacuna structure and the presence of fat-specific markers, respectively. To our knowledge, this is the first study comparing and demonstrating that the progenitor cells obtained from diverse surgical sites in hip replacement procedure share common characteristics of MSC but differ about plasticity and may provide rational for clinical application in cell therapy and bone grafting. The project number L1033 is registered with ClinicalTrials.gov NCT03369457.

Tendon repair is a challenging procedure in orthopaedics. The use of mesenchymal stem cells (MSCs) and pulsed electromagnetic fields (PEMF) in tendon regeneration is still investigational. In this perspective, MSCs isolated from the human umbilical cord (UC) may represent a possible candidate for tendon tissue engineering. The aim of the study is to evaluate the effect of low-frequency PEMF on tenogenic differentiation of MSCs isolated from the human umbilical cord (UC-MSCs) in vitro. 15 fresh UC samples from women with healthy pregnancies were retrieved at the end of caesarean deliveries. UC samples were manually minced into small fragments (less than 4 mm length) and cultured in MSC expansion medium. Part of the UC-MSCs was subsequently cultured with PEMF and tenogenic growth factors. UC-MSCs were subjected to pulsed electromagnetic fields for 2 h/day, 4 h/day, or 8 h/day. UC-MSCs cultured with FGF-2 and stimulated with PEMF showed a greater production of collagen type I and scleraxis. The prolonged exposure to PEMF was also related to the greatest expression of tenogenic markers. Thus, the exposure to PEMF provides a positive preconditioning biophysical stimulus, which may enhance UC-MSC tenogenic potential.

The treatment of painful chronic tendinopathy is challenging. Multiple non‐invasive and tendon‐invasive methods are used. When traditional non‐invasive treatments fail, the injections of platelet‐rich plasma autologous blood or cortisone have become increasingly favored. However, there is little scientific evidence from human studies supporting injection treatment. As the last resort, intra‐ or peritendinous open or endoscopic surgery are employed even though these also show varying results. This ESSKA basic science committee current concepts review follows the first part on the biology, biomechanics and anatomy of tendinopathies, to provide a comprehensive overview of the latest treatment options for tendinopathy as reported in the literature.