To evaluate the therapeutic effect of Pulsed Electromagnetic Field (PEMF) in the treatment of meniscal tears in the avascular region. Seventy-two twelve-week-old male Sprague-Dawley rats with full-thickness longitudinal medial meniscal tears in the avascular region were divided into 3 groups: control group (G. con. ), treated with classic signal PEMF (G. classic. ), and high slew rate signal PEMF(G. HSR. ). The HSR signal has the same pulse and burst frequencies as the classic signal, but with a higher slew rate. Macroscopic observation and histological analysis of the meniscus and articular cartilage were performed to evaluate the meniscal healing and progressions of osteoarthritis. The synovium was harvested for histological and immunofluorescent analysis to assess the intra-articular inflammation. The meniscal healing, articular cartilage degeneration, and synovitis were quantitatively evaluated according to their respective scoring system. Dramatic degenerative changes of the meniscus and articular cartilage were noticed during gross observation and histological evaluation in the control group at 8 weeks. However, the menisci in the two treatment groups were restored to normal morphology with a smooth surface and shiny white color. Particularly, the HSR signal remarkably enhanced the fibrochondrogenesis and accelerated the remodeling process of the regenerated tissue. The meniscal healing scores of PEMF treatment groups were significantly higher than those in the control group at 8 weeks. Specifically, the HSR signal showed a significantly higher meniscal repair score than the classic signal at week 8 (P < .01). The degeneration score (G. con. versus G. classic. : P < .0001; Gcon versus G. HSR. : P < .0001) and synovitis score (G. con. versus Gclassic: P < .0001; G. con. versus G. HSR. : P = .0002) of the control groups were significantly higher than those in the two treatment groups. PEMF promoted the healing of meniscal tears in the avascular region and restored the injured meniscus to its structural integrity in a rat model. Compared to the classic signal, the HSR signal showed the increased capability to promote fibrocartilaginous tissue formation and modulate the inflammatory environment and therefore protected the knee joint from post-traumatic osteoarthritis development

Objectives. Pulsed electromagnetic field (PEMF) stimulation was evaluated after anterior cervical discectomy and fusion (ACDF) procedures in a randomized, controlled clinical study performed for United States Food and Drug Administration (FDA) approval. PEMF significantly increased fusion rates at six months, but 12-month fusion outcomes for subjects at elevated risk for pseudoarthrosis were not thoroughly reported. The objective of the current study was to evaluate the effect of PEMF treatment on subjects at increased risk for pseudoarthrosis after ACDF procedures. Methods. Two evaluations were performed that compared fusion rates between PEMF stimulation and a historical control (160 subjects) from the FDA investigational device exemption (IDE) study: a post hoc (PH) analysis of high-risk subjects from the FDA study (PH PEMF); and a multicentre, open-label (OL) study consisting of 274 subjects treated with PEMF (OL PEMF). Fisher’s exact test and multivariate logistic regression was used to compare fusion rates between PEMF-treated subjects and historical controls. Results. In separate comparisons of PH PEMF and OL PEMF groups to the historical control group, PEMF treatment significantly (p < 0.05, Fisher’s exact test) increased the fusion rate at six and 12 months for certain high-risk subjects who had at least one clinical risk factor of being elderly, a nicotine user, osteoporotic, or diabetic; and for those with at least one clinical risk factor and who received at least a two- or three-level arthrodesis. Conclusion. Adjunctive PEMF treatment can be recommended for patients who are at high risk for pseudoarthrosis. Cite this article: D. Coric, D. E. Bullard, V. V. Patel, J. T. Ryaby, B. L. Atkinson, D. He, R. D. Guyer. Pulsed electromagnetic field stimulation may improve fusion rates in cervical arthrodesis in high-risk populations. Bone Joint Res 2018;7:124–130. DOI: 10.1302/2046-3758.72.BJR-2017-0221.R1

Radiofrequency (RF) lesions have been used for over 25 years in the treatment of intractable pain of spinal origin. The conventional understanding of this technique is that the heat which is produced in the tissue surrounding the electrode tip causes destruction of nervous tissue, which in turn reduces the input of noxious nerve stimuli and alleviates pain. Neuropathic pain is usually a contra-indication to the use of RF nerve lesioning. For treatment of patients with severe radicular pain we use pulsed radiofrequency who has been recently described as a technique to apply a relatively high voltage near a nerve but without the usual effects of rise in temperature or subsequent nerve injury. This study reports the effect of pulsed RF in 21 patients with severe radicular pain who had previously failed to respond to conventional therapy. Patients and Methods: From December 2000 to August 2001, 18 patients underwent pulsed RF Rhizotomy of Dorsal Root Ganglion (DRG) of segmental N. Root of the painful dermatome. Out of them, 16 passed treatment in the lumbar area and 2 in the neck. The age of the patients ranged from 20 to 75 years (m=55.7 years). Male/female ratio was 1.4/1. 50% was previously operated (discectomy, laminectomy). No complications were seen either in the procedure or in the follow-up. Results: Out of 21 patients, 3 (14.3%) did not respond to treatment. In the remaining 18 patients Rhizotomy was successful at 3 months follow-up. Mean VAS score before procedures was 8.85 (range 7–10), after treatment 3.8 (range 0–10). Conclusion: Pulsed RF treatment is a safe, simple procedure to control radicular, neuropathic pain in the cervical, thoracic and lumbar regions. Advantages of this method:. It is non-destructive procedure and it can therefore be used for different indication which were not suitable for conventional RF. Post-procedure discomfort does occur but it is less pronounced than following conventional RF. Although permanent sensory loss is a rare complication of RF it does occur. Pulsed RF does not have this complication

Unresolved inflammatory processes in tendon healing have been related to the progression of tendinopathies. Thus, the management of tendon injuries may rely on cell-based strategies to identify and modulate tendon inflammatory cues. Pulsed electromagnetic field (PEMF) has been approved by FDA for orthopedics therapies and has been related to a reduction in pain and to improve healing. However, the influence of PEMF in tendon healing remains largely unknown. Human tendon resident cells (hTDCs) were cultured in an inflammatory environment induced by exogenous supplementation of IL-1β and their response assessed after exposure to different PEMF treatments. This study demonstrates that IL-1β induced up-regulation of pro-inflammatory factors (IL-6 and TNFα) and extracellular matrix components (MMP−1, −2, −3) whereas reduces the expression of TIMP-1, suggesting IL-1β as a candidate inflammation model to study hTDCs response to inflammation cues. Moreover, in both homeostatic and inflammatory environments, hTDCs respond differently to PEMF treatment suggesting that cells are sensitive to magnetic field parameters such as strength (1.5 – 5mT), frequency (5–17Hz) and duration (10–50% duty cycle, dc). Among the conditions studied, PEMF treatment with 4mT/5Hz/50%dc suppresses the inflammatory response of hTDCs to the IL-1β stimulation, as evidenced by the decreases amount of IL-6, TNFα and downregulation of MMP-1, −2, −3 and COX-2, IL-8, IL-6, TNFα genes. These results demonstrate the potential of PEMF, in particular 4mT/5Hz/50%dc PEMF in treating tendon inflammation suppressing the inflammatory stimulation induced by IL-1β, which may be beneficial for tendon healing strategies

The purine nucleoside, adenosine regulates functions in every tissue and organ in the body acting via four G-protein-coupled receptors, A. 1. , A. 2A. , A. 2B. , and A. 3. adenosine receptors (ARs). Electromagnetic field (EMF) stimulation is an innovative therapeutic technique able to increase cellular anabolic activity and limit the catabolic effects of inflammatory cytokines. The mechanisms of cell reception of EMFs are not well known and much research activity has focused on the interactions between EMFs and membrane receptors. Interestingly, links have been found between ARs and their modulation by such physical agents as pulsed EMFs. EMF exposure mediates a significant upregulation of A. 2A. and A. 3. ARs in chondrocytes, synoviocytes and osteoblasts, leading to the reduction of synthesis and release of pro-inflammatory cytokines. In cultured full-thickness cartilage explants, pulsed EMFs preserve the integrity of the extracellular matrix and antagonize the effect of catabolic cytokines, such as IL-1. Pulsed EMFs, through the increase of ARs, enhance the working efficiency of adenosine without the side effects, desensitization, and receptor down-regulation often related to the use of agonist drugs. Modulation of adenosine receptors by pulsed EMFs could be a mechanism of cell reception of EMFs and an innovative physiologic alternative to the use of adenosine agonists

Electrical stimulation techniques are utilised in orthopedics field for the treatment of pseudoarthroses; the more widespread methods are the inductive system with Pulsed Electromagnetic Fields (PEMFs). We report the results of a retrospective study, between February 1987 to February 2002, of 57 patients with pseudoarthroses of tibia (22 treated with PEMFs against 35 without this treatment). The objectives of the study have been to know the influence, the consolidation percentage and the influence of electrical simulation. The average age was 38 years (14–89); the average follow-up 3,2 years. 17 fractures were open and 40 fractures were closed. All the fractures were affect the tibia shaft, in 19 cases extended to the articulation. For the admission to the study had not united after at less 6 month. All the patients were treated with surgery to the pseudoarthroses (looking nail in 54 cases, fixation extern in 2 cases and osteotomy to fibula in one case). Statistical analysis utilised was the SPSS program. The results were statistically significantly (p< 0,05) in:. The consolidation with the PEMFs increase compared without this method (91% vs 83%). The average time to consolidation decrease with the use to electrical stimulation compared to the patients treated without this treatment. Experience supports its role as a successful method of treatment for ununited fractures of the tibia

Pulsed Electromagnetic Fields (PEMFs) promote joint tissue anabolic activities, particularly in cartilage and bone. Here we investigated the effect of selected PEMFs (75Hz, 1.5mT, 1.3msec) in a differentiating model of murine myoblasts (C2C12) in vitro. C2C12 were seeded at 5×10. 3. cells/cm. 2. in 4 well plates and left to adhere for 24h. Subsequently, cells were either maintained in growth medium (GM) or induced towards myogenic differentiation in low-serum conditions, with and without PEMF exposure, for 4 days. Morphological analysis, myotube formation and fusion index (FI) were assessed with fluorescence microscopy techniques. Metabolic activity was determined by MTT; moreover, a multiplex cytokine array (RayBiotech) allowed cell supernatant molecule quantification. Cells exposed to PEMFs in GM acquired a distinctive elongated morphology, with increased bi-nuclear figures (3.2-fold FI increase over PEMF-unexposed cells) and displayed a significantly higher metabolic activity (+31%, p<0.05 over PEMF-unexposed cells). PEMF exposure increased metabolic activity also under myogenic differentiation (+15% over PEMF-unexposed differentiating cells, p<0.05), with the formation of long, thick polynuclear myotubes, suggesting a role of PEMFs in enhancing myogenesis (7.7-fold FI increase over PEMF-unexposed cells). 4-day culture supernatants revealed the presence of several myokines (KC/CXCL1, LIX, MCP-1, TIMP-1). Preliminary analysis showed a 1.16-fold increase (n=2) of LIX and, notably, a 1.91-fold increase (n=2) of TNF-RI, in cell supernatants of PEMF-exposed over PEMF-unexposed cells. Collectively, these results suggest that PEMF may successfully be applied in models of muscle cell trauma to optimise muscle fibre repair, by fine-tuning the release of myokines, promoting myoblast proliferation and myotube formation

Pulsed electromagnetic fields (PEMFs) have been considered a potential treatment modality for fracture healing. As bone fracture healing and osseointegration share the same biological events, the application of PEMF stimulation to facilitate the osseointegration process of orthopedic implants has been suggested. However, the mechanism of their action remains unclear. Mammalian target of rapamycin (mTOR) signaling may affect osteoblast proliferation and differentiation. This study aimed to assess the osteogenic differentiation of mesenchymal stem cells (MSCs) under PEMF stimulation and the potential involvement of mTOR signaling pathway in this process. PEMFs were generated by a novel miniaturized electromagnetic device (MED). Potential changes in the expression of mTOR pathway components, including receptors, ligands and nuclear target genes, and their correlation with osteogenic markers and transcription factors were analyzed. PEMF exposure increased cell proliferation, adhesion and osteogenic commitment of MSCs. Osteogenic-related genes were over-expressed following PEMF treatment. Our results confirm that PEMFs contribute to activation of the mTOR pathway via upregulation of the proteins AKT, MAPP kinase, and RRAGA, suggesting that activation of the mTOR pathway is required for PEMF-stimulated osteogenic differentiation. In summary, the findings of the present study revealed that MED-generated PEMFs stimulate osteogenic differentiation and the maturation of the adipose tissue-derived MSCs via activation of the mTOR pathways. Even though further research is required to determine an optimal stimulation timing and flux density both in-vitro and in-vivo, this study results may serve a source for an adjuvant therapy to improve orthopedic implant stability, longevity and enhance fracture healing

Wear of the ultra-high molecular weight polyethylene (UHMWPE) insert is one of the major issue related to orthopaedic implants. In this study, the tribo-mechanical properties of zirconia-coated UHMWPE deposited by means of Pulsed Plasma Deposition (PPD) technique were analyzed. Specifically, strength to local plastic deformation, indentation work portioning and creep behavior were evaluated through nanoindentation and micro-scratch tests, whereas preliminary wear data were obtained by tribology tests. A strong reduction of plastic deformation and a drop of the creep phenomenon for the zirconia-coated UHMWPE were evidenced, whereas - in spite of similar wear data - different wear mechanism was also detected. This study supported the use of hard ceramic thin films to enhance the mechanical performance of the plastic inserts used in orthopaedics

Introduction: The purpose of this prospective study was to evaluate the therapeutic value of Pulsed Electromagnetic Fields (PEMF) in the treatment of the osteonecrosis of the femoral head (ONFH). Materials and Methods: One hundred-eight consecutive hips with ONFH (80 patients) treated with PEMF between June 1990 and June 1998 were analyzed. The average age was 37 years. The average follow-up period was 6.9 years. According to the ARCO staging system, 3 hips were stage I, 85 hips stage II, and 20 hips stage III. Hips were evaluated clinically with a modified Harris hip scoring system and degree of pain relief. Radiographic progression was defined as either an advance in ARCO stage or progressive collapse of the femoral head more than 2 mm. Results: Clinical improvement was achieved in 81 hips (75%). Hip pain was relieved or decreased at an average of six months following initiation of PEMF therapy in the 81 hips with clinical improvement as well as some radiographically progressed hips. Radiographic progression was seen in 35 hips (32.4%). Total hip arthroplasty (THA) had been performed in 20 hips (18.5%). Kaplan-Meier survivorship analysis demonstrated that the probability of conversion to THA within 5 years after PEMF was 16% overall. Conversion to THA was significantly higher in patients who had the necrotic lesion laterally, in the subgroup C (more than 30% involvement of necrosis), and in patients older than the mean age. Discussion: These results demonstrate that PEMF can modifiy the natural course of ONFH. PEMF is recommended in patients who are less than forty years old with early stage disease with small necrotic involvement. Refinement of PEMF could make it a more efficacious non-invasive method of treatment

Introduction. Protective hard coatings are appealing for several technological applications like solar cells, organic electronics, fuel cells, cutting tools and even for orthopaedic implants and prosthetic devices. At present for what concerns the application to prosthetic components, the coating of the surface of the metallic part with low-friction and low-wear materials has been proposed [1]. Concerning the use of ceramic materials in joint arthroplasty, zirconia-toughned-alumina (ZTA) reported high strength, fracture toughness, elasticity, hardness, and wear resistance [2]. The main goal of this study was to directly deposit ZTA coating by using a novel sputter-based electron deposition technique, namely Pulsed Plasma Deposition (PPD) [3]. The realized coatings have been preliminary characterized from the point of view of morphology, wettability, adhesion and friction coefficients. Materials and methods. ZTA coatings were deposited by PPD technique, which is able to maintain the stoichiometry of the starting target. In this case we started from a cylindrical ZTA target (30 mm diameter × 5 mm thickness, 75% alumina / 25% zirconia). The morphology, micro-structure and chemistry of deposited coatings were characterized by Scanning Electron Microscopy (SEM) equipped with Energy Dispersive X-ray Spectrosopy (EDS) and Atomic Force Microcscope (AFM). Coating-substrate interface quality were investigated by microscratch tests. The degree of wetting was estimated by measuring the contact angle between a drop of 1 ml of ultrapure water and the surface of the sample. Preliminary ball-on-disk tribological tests were carried out in air and deionized water coupling ZTA-coated stainless steel ball (AISI 420, 3 mm radius, grade 200) against medical grade UHMWPE to evaluate the friction of the proposed coupling. Results. Deposited ZTA films exhibited a smooth nanostructured surface. Coatings up to several microns thick have been deposited by PPD [Fig. 1 – SEM image (left) and cross section (right)]. Mechanical tests showed a well-adherent films were deposited. In particular, the good interface adhesion was assessed by scratch tests, reporting at about 0.8 N the first formation of cracking in the coating during testing. The contact angles revealed an hydrophobic behavior of the coating (average contact angle 116° ± 2°), probably due to the nano-roughness of the coating itself [Fig. 2 – Contact angle]. Preliminary tribological tests carried out in deionized water after up to 10000 m tracks showed good average friction coefficient ranging from 0.12 to 0.15 [Fig. 3 – Friction coefficient]. Conclusions. We have presented the preliminary results of a novel approach aiming to the drastically improve the performance of prosthetic couplings by introducing hard ceramic coating. The results showed suggested the feasibility of pursuing this approach of realizing ZTA coatings by means of PPD technique. Further analyese on mechanical properties, nano-roughness and tribology should be performed. Well-adherent ZTA films deposited directly on the surface of prosthetic components of a joint implant would then allow a drastic improvement of the actual prosthetic behaviour

Introduction. Protective hard coatings are appealing for several technological applications and even for orthopaedic implants and prosthetic devices. For what concerns the application to prosthetic components, coating of the surface of the metallic part with low-friction and low-wear materials has been proposed [1, 2]; at the same time, concerning use of ceramic materials in joint arthroplasty, zirconia-toughned-alumina (ZTA) ceramic material has shown high strength, fracture toughness, elasticity, hardness, and wear resistance [3, 4]. The purpose of this study was to directly deposit ZTA coatings by using a novel sputter-based electron deposition technique, namely Pulsed Plasma Deposition (PPD) [5]. Preliminary characterization of realized coatings from the point of view of morphology, wettability, adhesion and friction coefficients was performed. Materials and methods. PPD technique was used to deposit ZTA coatings; this technique is able to maintain the stoichiometry of the starting target. In this study we started from a cylindrical ZTA target (30 mm diameter × 5 mm thickness, 75% alumina / 25% zirconia) and followed the procedure described by Bianchi et al [5]. Characterization of morphology, micro-structure and chemistry of deposited coatings was performed by Scanning Electron Microscopy (SEM) equipped with Energy Dispersive X-ray Spectroscopy (EDS) and Atomic Force Microscope (AFM). Coating-substrate interface quality were investigated by micro-scratch tests. Measurement of the contact angle between a drop of 1 ml of ultrapure water and the surface of the sample was performed to estimate the degree of wetting. A ZTA-coated stainless steel ball (AISI 420, 3 mm radius) was coupled against medical grade UHMWPE to evaluate the friction of the proposed coupling in preliminary ball-on-disk tribological tests. Results. Coatings up to several microns thick have been deposited by PPD. Deposited ZTA films exhibited a smooth nanostructured surface. Mechanical tests showed a well-adherent films were deposited. In particular, scratch tests assessed a good interface adhesion: first formation of cracking in the coating during testing was reported at about 0.8 N. Hydrophobic behavior of the coating was revealed by contact angles (average contact angle 116° ± 2°), probably due to the nano-roughness of the coating itself. Good average friction coefficient ranging from 0.12 to 0.15 was showed by preliminary tribological tests carried out in deionized water after up to 10000 m tracks. Conclusions. The preliminary results of a novel approach aiming to drastically improve the performance of prosthetic couplings by introducing hard ceramic coating was presented. Showed results suggested the feasibility of pursuing this approach of realizing ZTA coatings by means of PPD technique. Further analyses on mechanical properties, nanoroughness and tribology are ongoing. Well-adherent ZTA films deposited directly on the prosthetic components surface would then allow a drastic improvement of the actual prosthetic behaviour

Animal studies examining tendon-bone healing have demonstrated that the overall structure, composition, and organization of direct type entheses are not regenerated following repair. We examined the effect of Low-Intensity Pulsed Ultrasound (LIPUS) on tendon-bone healing. LIPUS may accelerate and augment the tendon-bone healing process through alteration of critical molecular expressions. Eight skeletally mature wethers, randomly allocated to either control group (n=4) or LIPUS group (n=4), underwent rotator cuff surgery following injury to the infraspinatus tendon. All animals were sacrificed 28 days post surgery to allow examination of early effects of LIPUS. Humeral head – infraspinatus tendon constructs were harvested and processed for histology and immunohistochemical staining for BMP2, Smad4, VEGF and RUNX2. All the growth factors were semiquantitative evaluated. T-tests were used to examine differences which were considered significant at p < 0.05. Levene's Test (p < 0.05) was used to confirm variance homogeneity of the populations. The surgery and LIPUS treatment were well tolerated by all animals. Placement of LIPUS sensor did not unsettle the animals. Histologic appearance at the tendon-bone interface in LIPUS treated group demonstrated general improvement in appearance compared to controls. Generally a thicker region of newly formed woven bone, morphologically resembling trabecular bone, was noted at the tendon-bone interface in the LIPUS-treated group compared to the controls. Structurally, treatment group also showed evidence of a mature interface between tendon and bone as indicated by alignment of collagen fibres as visualized under polarized light. Immunohistochemistry revealed an increase in the protein expression patterns of VEGF (p = 0.038), RUNX2 (p = 0.02) and Smad4 (p = 0.05) in the treatment group. There was no statistical difference found in the expression patterns of BMP2. VEGF was positively stained within osteoblasts in newly formed bone, endothelial cells and some fibroblasts at the interface and focally within fibroblasts around the newly formed vessels. Expression patterns of RUNX2 were similar to that of BMP-2; the staining was noted in active fibroblasts found at the interface as well as in osteoblast-like cells and osteoprogenitor cells. Immunostaining of Smad4 was present in all cell types at the healing interface. The results of this study indicate that LIPUS may aid in tendon to bone healing process in patients who have undergone rotator cuff repair. This treatment may also be beneficial following other types of reconstructive surgeries involving the tendon-bone interface

Aims

In the context of tendon degenerative disorders, the need for innovative conservative treatments that can improve the intrinsic healing potential of tendon tissue is progressively increasing. In this study, the role of pulsed electromagnetic fields (PEMFs) in improving the tendon healing process was evaluated in a rat model of collagenase-induced Achilles tendinopathy.

Tibial shaft fractures have a high incidence of delayed and non-union, often requiring multiple procedures. Pulsed electromagnetic field (PEMF) stimulation is a safe and effective treatment for tibial non union but little is known about the efficacy of PEMF in preventing non-union in acute fractures. Between August 2005 and December 2008, eligible patients presenting at six major metropolitan hospitals with acute tibial shaft fractures (AO classification 4-2) were included. Participants were randomised by an independent allocation centre to identical active or inactive PEMF devices, both prescribed to be worn ten hours daily for twelve weeks. Baseline data were collected, and patients and surgeons were surveyed serially via post and/or phone at three, six and twelve months. Participants, data collectors and data analysts were blinded. The main outcome was any surgical intervention for delayed/non union. Data from 150 patients (76 active and 74 inactive) were available for analysis (12 month follow up 78%). There was no between-group difference in age, gender, mechanism of injury, open grade, smoking status, or compliance with the device (hours of use). Overall compliance was moderate (5.7 hours daily use). Fifteen of 76 (20%) of active device patients required surgery for delayed/non-union vs. 8 of 74 (11%) in the placebo group; odds ratio of surgery=2.03, p=0.13, 95% CI 0.80 to 5.12. An intention to treat analysis adjusted for open grade and hours the device was used showed an odds ratio of requiring surgery of 1.78 (p=0.24, 95% CI 0.68 to 4.64). A sub-group analysis of 80 compliant patients (defined a priori as a minimum average of six hours daily use) was performed. Nine of 35 (26%) patients with an active device required surgery for delayed/non-union vs. 3 of 45 (7%) in the placebo group; odds ratio of surgery=7.60 (p=0.017, 95% CI 1.43 to 40.24). Based on these unexpected initial results, PEMF stimulation does not prevent revision surgery for delayed/non-union in acute fractures of the tibial shaft

Abstract

Introduction

Articular cartilage injuries have a limited potential to heal and, over time, may lead to osteoarthritis, an inflammatory and degenerative joint disease associated with activity-related pain, swelling, and impaired mobility. Regeneration and restoration of the joint tissue functionality remain unmet challenges. Stem cell-based tissue engineering is a promising paradigm to treat cartilage degeneration. In this context, hydrogels have emerged as promising biomaterials, due to their biocompatibility, ability to mimic the tissue extracellular matrix and excellent permeability. Different stimulation strategies have been investigated to guarantee proper conditions for mesenchymal stem cell differentiation into chondrocytes, including growth factors, cell-cell interactions, and biomaterials. An interesting tool to facilitate chondrogenesis is external ultrasound stimulation. In particular, low-intensity pulsed ultrasound (LIPUS) has been demonstrated to have a role in regulating the differentiation of adipose mesenchymal stromal cells (ASCs). However, chondrogenic differentiation of ASCs has been never associated to a precisely measured ultrasound dose. In this study, we aimed to investigate whether dose-controlled LIPUS is able to influence chondrogenic differentiation of ASCs embedded in a 3D hydrogel.

Introduction and Objective

Nonunion is incomplete healing of fracture and fracture that lacks potential to heal without further intervention. Nonunion commonly presents with persistent pain, swelling, or instability. Those symptoms affect patient quality of life. It is known that using low intensity pulsed ultrasound (LIPUS) for fresh fractures promotes healing. However, effectiveness of LIPUS for nonunion is still controversial. If LIPUS is prove to be effective for healing nonunion, it can potentially provide an alternative to surgery. In addition, we can reduce costs by treating nonunion with LIPUS than performing revision surgery.

Summary:

Hamstring tendons (HT) represent a widely used autograft for ACL reconstruction. Harvesting, processing and pretensioning procedures together with the time out of the joint could theoretically hamper tendon cells (TCs) viability. The authors hypothesize that HT cells are not impaired at the end of the surgical procedures and their tenogenic phenotype may be strongly improved by exposure to PEMF.

Staphylococcus aureus is responsible for 60–70% infections of surgical implants and prostheses in Orthopaedic surgery, with cumulative treatment costs for all prosthetic joint infections estimated to be ∼ $1 billion per annum (UK and North America). Its ability to develop resistance or tolerance to a diverse range of antimicrobial compounds, threatens to halt routine elective implant surgery. One strategy to overcome this problem is to look beyond traditional antimicrobial drug therapies and investigate other treatment modalities. Biophysical modalities, such as ultrasound, are poorly explored, but preliminary work has shown potential benefit, especially when combined with existing antibiotics. Low intensity pulsed ultrasound is already licensed for clinical use in fracture management and thus could be translated quickly into a clinical treatment

Using a methicillin-sensitive S. aureus reference strain and the dissolvable bead assay, biofilms were challenged with gentamicin +/− low-intensity ultrasound (1.5MHz, 30mW/cm2, pulse duration 200µs/1KHz) for 180 minutes and 20 minutes, respectively. The primary outcome measures were colony-forming units/mL (CFU/mL) and the minimum biofilm eradication concentration (MBEC) of gentamicin. The mean number of S. aureus within control biofilms was 1.04 × 109 CFU/mL. Assessment of cellular metabolism was conducted using a liquid-chromatography-mass spectrometry, as well as a triphenyltetrazolium chloride assay coupled with spectrophotometry.

There was no clinically or statistically significant (p=0.531) reduction in viable S. aureus following ultrasound therapy alone. The MBEC of gentamicin for this S. aureus strain was 256 mg/L. The MBEC of gentamicin with the addition of ultrasound was reduced to 64mg/L. Metabolic activity of biofilm-associated S. aureus was increased by 25% following ultrasound therapy (p < 0 .0001), with identification of key biosynthetic pathways activated by non-lethal dispersal.

Low intensity pulsed ultrasound was associated with a four-fold reduction in the effective biofilm eradication concentration of gentamicin, bringing the MBEC of gentamicin to within clinically achievable concentrations. The mechanism of action was due to partial disruption of the extracellular matrix which led to an increase of nutrient availability and oxygen tension within the biofilm. This metabolic stimulus was responsible for the reversal of gentamicin tolerance in the biofilm-associated S. aureus.