Recent studies suggested that both the soluble protein of the mesenchymal stromal cell (MSC) secretome, as well as the secreted extracellular vesicles (EVs) promote bone regeneration. However, there is limited knowledge of the changes in MSC secretome vesicular fraction during aging. We therefore aimed to characterize the
Introduction and Objective. The continued effectiveness of antibiotic loaded bone cements is threatened by antibiotic resistance. The common antiseptic, chlorhexidine (CHX), is a potential alternative to antibiotics in bone cements, but conventional salts are highly soluble, causing burst
The recent description of progenitor/stem cells in degenerated intervertebral discs (IVDs) raised the possibility of harnessing their regenerative capacity for endogenous repair. The aim of this work is to develop an intradiscal polysaccharide microbead-based delivery system for the sequential
To prevent infections after orthopedic surgery, intravenous antibiotics are administered perioperatively. Cefazolin is widely used as the prophylactic antibiotic of choice. Systemic antibiotic therapy may however be less effective in longstanding surgery where bone allografts are used. Bone chips have been shown to be an effective carrier for certain types of antibiotics. Bone allografts impregnated with antibiotics may therefore provide the necessary local antibiotic levels for prophylaxis. To be efficient, a prolonged
Introduction and Objective. Carpal tunnel syndrome (CTS) is a very common compressive neuropathy involving the median nerve. The typical symptoms are paraesthesia, dysesthesia and loss of strength; in severe case, this compression deteriorates the sensorimotor control of the hand and interferes with the adjustment of the forces at the level of the fingers, thus affecting the components that are the basis of dexterity and control of fine movements. For these reasons, the CTS has repercussions on various activities of daily life, including writing skills. Word processing via PC and mobile device (touch-typing) require a fine control of the hand-wrist movement and of the opposition of the thumb, while in handwriting, gripping and gripping movements are carried out in a protracted manner. In modern society, present skills play a role of fundamental importance from an educational, professional and social point of view. The aim of the study is to describe the effects of carpal tunnel
Aseptic loosening is a major cause of revision surgeries and occurs when osteolysis is stimulated around the implant by pro-inflammatory cytokines including IL-1β. Production of active IL-1β in response to orthopedic wear particles depends on processing by the NLRP3 inflammasome which requires priming followed by activation. We found that pathogen associated molecular patterns (PAMPs) adherent to wear particles are necessary to prime the NLRP3 inflammasome. In contrast, in pre-primed macrophages, particles themselves are sufficient to activate the NLRP3 inflammasome and induce secretion of active IL-1β. Particles themselves also induce cell death, kinetically preceding the
Articular cartilage is often damaged, and its treatment is usually performed by surgical operation. Today, tissue engineering offers an alternative treatment option for injuries or diseases with increasing importance. Infrapatellar fat pad (IPFP) is a densely vascularized and innervated extra synovial tissue that fills the anterior knee compartment. Adipose-derived stem cells from infrapatellar fat pad (IPFP-ASCs) have multipotency means that they can differentiate into connective tissue cells and have age-independent differentiation capacity as compared to other stem cells. In this study, the osteochondral tissue construct was designed with different inner pattern due to original osteochondral tissue structure and fabrication of it was carried out by 3D printing. For this purpose, alginate (3% w/v) and carboxymethylcellulose (CMC) (9%w /v) were used as bioink. Also, IPFP-ASCs were isolated with enzymatic degradation. Osteogenic and chondrogenic differentiation of IPFP-ASCs were investigated with Alizarin Red and Alcian Blue staining, respectively. IPFP-ASCs-laden osteochondral graft differentiation will be induced by controlled
Background. The doses of local rhBMP-2 in commercially available materials are high with known drawbacks such as inflammation and premature bone resorption. The latter can be prevented by adding bisphosphonates like zoledronic acid (ZA) but systemic ZA has side effects and patient adherence to treatment is low. In a recent study, we have shown that local co-delivery of rhBMP-2 and ZA via a calcium sulphate/hydroxyapatite (CS-HA) biomaterial can be used to regenerate both cortical and trabecular bone in a rat model of metaphyseal bone defect. Even low doses of local ZA in the biomaterial showed promising results and increased bone formation within the defect compared to the controls. A step before clinical translation of the local treatment regimen is to evaluate the in-vivo
Aims. Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular
The aim of this study is to compare the
Total knee arthroplasty is a well-established treatment for degenerative joint disease, on the other hand metal ion
Introduction. Prosthetic joint infections (PJI) occur infrequently, but due to its increased clinical use represent the most devastating complication with high morbidity and substantial cost. Staphylococcus aureus and coagulase-negative staphylococci are the most common infecting agents associated with PJI. A possible therapeutic approach could be the local antibiotic by fluoride-TiO2 nanostructured anodic layers in order to prevent surface colonisation during the early moments after surgery. Here we describe the first results of this model using two common antibiotics. Methods. Fluoride-TiO2 nanostructured anodic layers on Ti6Al4V alloy were produced as described previously by Arenas et al (2013). Discs shaped pieces of Ti6Al4V alloy were loaded with a solution of 150 mg antibiotic (vancomycin or gentamicin)/20 ml sterile distilled water. Samples were immersed in this solution during 24 hours at room temperature with agitation, and then were dried during 48 hours at 20°C. Antibiotic
Although the response of macrophages to polyethylene debris has been widely studied, it has never been compared with the cellular response to ceramic debris. Our aim was to investigate the cytotoxicity of ceramic particles (Al. 2. O. 3. and ZrO. 2. ) and to analyse their ability to stimulate the
Total knee arthroplasty is a well established treatment for degenerative joint disease with good clinical results. However, complications may occur due to a biological response to polyethylene wear particles, leading to osteolysis and aseptic loosening, as well as local and systemic hypersensitivity reactions triggered by metal ions and particles such as chromium, cobalt and molybdenum. Moreover, there is an increasing demand on the performance of these implants, as this treatment is also performed in heavier, younger and middle-aged adults who have a significant physical activity and higher life expectancy. The purpose of the following study was to compare the wear characteristics and performance of a zirconium nitride (ZrN) coated knee implant, designed for patients with metal ion hypersensitivity, against the clinically established cobalt-chromium (CoCr) version under a high demanding activities wear simulation. Medium size AS Columbus® DD (Aesculap AG, Tuttlingen, Germany) femoral and tibial components with a ZrN surface were tested in comparison with the cobalt-chromium version Columbus® DD. For both groups, ultra-high-molecular weight polyethylene (UHMWPE) gliding surfaces (size T3, high 10 mm) were used. Wear simulation was performed on a load controlled 4 station knee wear simulator (EndoLab GmbH, Thansau, Germany) capable of reproducing loads and movement of daily activities measured in vivo (Bergmann et al, 2014) on 8 patients and normalized to a patient weight of 100 kg (Schwiesau et al, 2014). The load profiles were applied for 5 million cycles in a combination of 40% stairs up, 40% stairs down, 10% level walking, 8% chair raising and 2% deep squatting. Test serum was changed every 0.5 million cycles and all the components were cleaned and analyzed according to ISO 14243-2:2009(E). The gliding surfaces were evaluated for gravimetric wear and wear patterns, femur components analyzed for scratches and the test medium analyzed for metal ion concentration (cobalt, chromium, molybdenum and zirconium) using ICP-MS according to ISO 17294-2. The present study showed a wear rate reduction for the ZrN group (1.01 ± 0.29 mg/million) in comparison with the CoCr group (2.40 ± 1.18 mg/million cycles). The articulation surface of the ZrN coated femurs remained polished after the testing period, whereas the uncoated femurs showed wear scratches. Furthermore, the metal ion
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
Purpose. Gustilo type III open fractures are associated with high infection rates in spite of instituting a standard of care (SOC) consisting of intravenous antibiotics, irrigation and debridement (I&D), and delayed wound closure. Locally-delivered antibiotic has been proven to assist in reducing infection in open fractures. The aims of this study are to determine the effectiveness and safety of a new implantable and biodegradable antibacterial product. 1. in preventing bacterial infections and initiating bone growth in open fractures. Methods. The osteoconductive antibacterial BonyPid. TM. used is a synthetic bone void filler (comprised of ≤1 mm β-tricalcium phosphate granules) coated by a thin layer (≤20 µm) of PolyPid nanotechnology formulation. −. Upon implantation, the coating
The clinical translation of regenerative therapies, whether in the form of mesenchymal cells, macromolecules or small molecules, is hampered by several factors: the poor retention and short biological half-life of the therapeutic agent, the adverse side effects from systemic delivery, and difficulties with the administration of multiple doses to a target site. We report the development and application of a therapeutic reservoir device that enables sustained and repeated administration of small molecules, macromolecules and cells directly to organs and tissues of interest via a polymer-based reservoir connected to a subcutaneous port. In a myocardial infarct rodent model, we show that repeated administration of cells over a four-week period using the reservoir provided functional compared to a single injection of cells and to no treatment. Recent advances of the system include a multi-port and multi-reservoir system that can be tailored to cargo and application need. The pre-clinical use of our therapeutic reservoir as a research model may enable insights into regenerative orthopaedic therapy, particularly those therapies that require multi-dose approaches.
For many years, minimally invasive joint-preserving regenerative therapy has been desired for the early stages of osteonecrosis of the femoral head (ONFH). In an animal study using adult rabbits, we reported that a single local injection of rhFGF-2-impregnated gelatin hydrogel, which has superior slow-release characteristics, suppresses the progression of femoral head necrosis. The purpose of this study was to evaluate the safety and clinical outcomes of a single local administration of rhFGF-2-impregnated gelatin hydrogel for the precollapse stage of ONFH. Patients and Methods: Ten patients with femoral heads up to precollapse stage 2 underwent a single local administration of 800-µg rhFGF-2-impregnated gelatin hydrogel and were followed up for two years. The eligibility criteria were age between 20 and 80 years and presence of ONFH at precollapse stage 1 or 2 according to the classification system for ONFH developed by the Japanese Investigation Committee of Health and Welfare. Primary outcomes included adverse events and complications. Secondary outcomes included changes in Harris Hip Scores (HHS), visual analog scale pain scores (VAS), the University of California, Los Angeles (UCLA) activity rating scores, radiological changes as determined via radiographs, computed tomography (CT) scans, and magnetic resonance imaging (MRI) of the hip joint. Results: We included five men (five hips) and five women (five hips), with a mean age of 39.8 years (range: 29–53 years) at the time of surgery. Eight patients had bilateral ONFH, three had already undergone THA on the contralateral side. Eight patients were receiving treatment with corticosteroid therapy, and two patients overused alcohol. Stage 1 and 2 disease was present in one and nine patients, respectively. One patient each had type A, type B, and type C1 disease, whereas seven patients had a type C2 lesion. All Adverse events were recovered without problem. The surgery was performed with a minimally invasive technique based core decompression (1 cm of skin incision), and walking was allowed from the day after surgery. Mean clinical scores improved significantly after three year compared with before surgery (before vs. after: VAS for pain, 21.2 vs. 5.3 mm; UCLA activity score 5.5 vs. 6.6; HHS, 81.0 vs. 98.4 points, respectively). There was only one case of femoral head collapse, and it had the greatest necrosis volume fraction and was considered to be in the early collapse stage at the time of operation. The other nine cases did not involve ONFH stage progression, and collapse was prevented. CT images and recent MRI postoperatively confirmed bone regeneration and reduction of the necrotic area. Conclusion: Clinical application of rhFGF-2-impregnated gelatin hydrogel for patients with precollapse stage of ONFH was feasible and safe. Our research is ongoing, further phase II multiple center study has been started in January 2016.Introduction
Summary. Management of metal on metal hip replacements can be accomplished with a simple algorithm including easily available metal ion levels and hip MRI with metal artifact reducing software. After revision serum metal ion levels can be expected to fall rapidly. Introduction. Metallic ion
Tendon cross-sectional area (CSA) and stiffness increase in men during chronic exercise. The increase in tendon CSA and stiffness is not evident in women. In men, exercise increases tendon production of MMPs, IGF-1, and IL-6, which presumably contribute to tendon remodeling during chronic exercise. The purpose of this study was to determine if exercise-induced production of MMPs, IGF-1, and IL-6 are limited in women when compared to men. Young men (n=9, 27±1 y) and women (n=8, 26±1 y) performed a single bout of calf press exercise (8 sets of 15 repetitions at 70% of 15-RM). A microdialysis fiber (3000 kDa cut-off) was inserted into the space anterior to the Achilles tendon immediately after exercise and during a control experiment. All proteins were evaluated with ELISA kits.Introduction
Materials and Methods