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Purpose Platelet-rich plasma (PRP) is currently the most exploited strategy in the clinical practice to provide a regenerative stimulus for tendon healing. The aim of the present study was to systematically review the available evidence on the treatment of the main tendon disorders where PRP is currently applied. Methods A systematic review of the literature was performed on the use of PRP as a treatment for tendinopathies focusing on the following sites: Achilles tendon, patellar tendon, rotator cuff tendons, and lateral elbow tendons. The following inclusion criteria for relevant articles were used: clinical trials written in English language up to 21 June 2016 on the use of PRP in the conservative or surgical treatment of the aforementioned tendinopathies. Results The research identified the following clinical trials dealing with the application of PRP in the selected tendons: 19 papers on patellar tendon (6 being RCTs: 4 dealing with PRP conservative application and 2 surgical), 24 papers on Achilles tendon (4 RCTs: 3 conservative and 1 surgical), 29 on lateral elbow tendons (17 RCTs, all conservative), and 32 on rotator cuff (22 RCTs: 18 surgical and 3 conservative). Conclusion Patellar tendons seem to benefit from PRP injections, whereas in the Achilles tendon, PRP application is not indicated neither as a conservative approach nor as a surgical augmentation. Lateral elbow tendinopathy showed an improvement in most of the high-level studies, but the lack of proven superiority with respect to the more simple whole-blood injections still questions its use in the clinical practice. With regard to rotator cuff pathology, the vast majority of surgical RCTs documented a lack of beneficial effects, whereas there is still inconclusive evidence concerning its conservative application in rotator cuff disorders. Level of evidence Systematic review of level I–IV trials, Level IV.

The therapeutic ability of Mesenchymal Stem/Stromal Cells to address osteoarthritis (OA) is mainly related to the secretion of biologically active factors, which can be found within their secreted Extracellular Vesicles including small Extracellular Vesicles (sEV). Aim of this study was to investigate the effects of sEV from adipose derived stromal cells (ADSC) on both chondrocytes and synoviocytes, in order to gain insights into the mechanisms modulating the inflammatory/catabolic OA environment. sEV, obtained by a combined precipitation and size exclusion chromatography method, were quantified and characterized, and administered to chondrocytes and synoviocytes stimulated with IL-1β. Cellular uptake of sEV was evaluated from 1 to 12 h. Gene expression and protein release of cytokines/chemokines, catabolic and inflammatory molecules were analyzed at 4 and 15 h, when p65 nuclear translocation was investigated to study NF-κB pathway. This study underlined the potential of ADSC derived sEV to affect gene expression and protein release of both chondrocytes and synoviocytes, counteracting IL-1β induced inflammatory effects, and provided insights into their mechanisms of action. sEV uptake was faster in synoviocytes, where it also elicited stronger effects, especially in terms of cytokine and chemokine modulation. The inflammatory/catabolic environment mediated by NF-κB pathway was significantly attenuated by sEV, which hold promise as new therapeutic strategy to address OA.

● Au, Ag and Pd were recovered from WPCBs with high efficiencies. ● Au leaching is strictly dependent on WPCB size and reagent concentration. ● High Ag extraction efficiencies are achieved regardless of the WPCB size. ● Pd leaching works better with small and medium WPCB sizes. ● The leaching results suggest the possibility of selective recovery of metals. The work presented here focused on the extraction of gold (Au), silver (Ag) and palladium (Pd) from electronic waste using a solution of ammonium thiosulfate. Thiosulfate was used as a valid alternative to cyanide for precious metal extractions, due to its non-toxicity and high selectivity. The interactions between sodium thiosulfate, total ammonia/ammonium, precious metal concentrations and the particle size of the waste printed circuit boards (WPCBs) were studied by the response surface methodology (RSM) and the principal component analysis (PCA) to maximize precious metal mobilization. Au extraction reached a high efficiency with a granulometry of less than 0.25 mm, but the consumption of reagents was high. On the other hand, Ag extraction depended neither on thiosulfate/ammonia concentration nor granulometry of WPCBs and it showed efficiency of 90% also with the biggest particle size (0.50 < Ø < 1.00 mm). Pd extraction, similarly to Au, showed the best efficiency with the smallest and the medium WPCB sizes, but required less reagents compared to Au. The results showed that precious metal leaching is a complex process (mainly for Au, which requires more severe conditions in order to achieve high extraction efficiencies) correlated with reagent concentrations, precious metal concentrations and WPCB particle sizes. These results have great potentiality, suggesting the possibility of a more selective recovery of precious metals based on the different granulometry of the WPCBs. Furthermore, the high extraction efficiencies obtained for all the metals bode well in the perspective of large-scale applications.

Tendinopathies are common overuse disorders that arise both in athletes and the general population. Available tendon treatments are used both for women and men without distinction. However, the existence of a sex-based difference in tendon biology is widely demonstrated. Since basic research represents the foundation for treatment development, an equal female–male representation should be pursued in preclinical studies. This systematic review quantified the current evidence by analyzing 150 studies on 8231 animals. Preclinical studies largely neglected the importance of sex, none analyzed sex-based differences, and only 4% of the studies reported disaggregated data suitable for the analysis of treatment results in males and females. There is an alarming female under-representation, in particular in the field of injective therapies. Despite the growing awareness on the importance of investigating treatments in both males and females, the investigated field proved resistant from properly designing studies including both sexes, and the lack of sex-representation remains critical. Highlights Tendinopathy has sex-specific features, with sex hormones affecting tendon metabolism, structure, biomechanical properties, and injury risk. The preclinical research on tendinopathy treatments still neglects sex-based differences, leading to translation of male data to females which may affect clinical effectiveness in women. None of the reviewed studies looked at differences between sexes, and only 4% of the studies reported disaggregated data. Besides, female animals are under-represented. The lack of sex-representation in tendinopathy research remains critical.

The last decade has seen exponentially growing efforts to exploit the effects of adipose derived stromal cells (ADSC) in the treatment of a wide range of chronic degenerative diseases, including osteoarthritis (OA), the most prevalent joint disorder. In the perspective of developing a cell-free advanced therapy medicinal product, a focus has been recently addressed to the ADSC secretome that lends itself to an allogeneic use and can be further dissected for the selective purification of small extracellular vesicles (sEVs). sEVs can act as “biological drug carriers” to transfer information that mirror the pathophysiology of the providing cells. This is important in the clinical perspective where many OA patients are also affected by the metabolic syndrome (MetS). ADSC from MetS OA patients are dysfunctional and “inflammatory” primed within the adipose tissue. To mimic this condition, we exposed ADSC to IL-1β, and then we investigated the effects of the isolated sEVs on chondrocytes and synoviocytes, either cultured separately or in co-culture, to tease out the effects of these “IL-1β primed sEVs” on gene and protein expression of major inflammatory and catabolic OA markers. In comparison with sEVs isolated from unstimulated ADSC, the IL-1β primed sEVs were able to propagate NF-κB activation in bystander joint cells. The effects were more prominent on synoviocytes, possibly because of a higher expression of binding molecules such as CD44. These findings call upon a careful characterization of the “inflammatory fingerprint” of ADSC to avoid the transfer of an unwanted message as well as the development of in vitro “preconditioning” strategies able to rescue the antiinflammatory/anticatabolic potential of ADSC-derived sEVs.

Platelet-Rich Plasma (PRP) is a low-cost procedure to deliver high concentrations of autologous growth factors (GFs). Platelet activation is a crucial step that might influence the availability of bioactive molecules and therefore tissue healing. Activation of PRP from ten voluntary healthy males was performed by adding 10% of CaCl2, 10% of autologous thrombin, 10% of a mixture of CaCl2 + thrombin, and 10% of collagen type I. Blood derivatives were incubated for 15 and 30 minutes and 1, 2, and 24 hours and samples were evaluated for the release of VEGF, TGF-β1, PDGF-AB, IL-1β, and TNF-α. PRP activated with CaCl2, thrombin, and CaCl2/thrombin formed clots detected from the 15-minute evaluation, whereas in collagen-type-I-activated samples no clot formation was noticed. Collagen type I produced an overall lower GF release. Thrombin, CaCl2/thrombin, and collagen type I activated PRPs showed an immediate release of PDGF and TGF- β 1 that remained stable over time, whereas VEGF showed an increasing trend from 15 minutes up to 24 hours. CaCl2 induced a progressive release of GFs from 15 minutes and increasing up to 24 hours. The method chosen to activate PRP influences both its physical form and the releasate in terms of GF amount and release kinetic.

Mitochondrial calcium uniporter (MCU) channel is responsible for Ruthenium Red‐sensitive mitochondrial calcium uptake. Here, we demonstrate MCU oligomerization by immunoprecipitation and Förster resonance energy transfer (FRET) and characterize a novel protein (MCUb) with two predicted transmembrane domains, 50% sequence similarity and a different expression profile from MCU. Based on computational modelling, MCUb includes critical amino‐acid substitutions in the pore region and indeed MCUb does not form a calcium‐permeable channel in planar lipid bilayers. In HeLa cells, MCUb is inserted into the oligomer and exerts a dominant‐negative effect, reducing the [Ca 2+ ] mt increases evoked by agonist stimulation. Accordingly, in vitro co‐expression of MCUb with MCU drastically reduces the probability of observing channel activity in planar lipid bilayer experiments. These data unveil the structural complexity of MCU and demonstrate a novel regulatory mechanism, based on the inclusion of dominant‐negative subunits in a multimeric channel, that underlies the fine control of the physiologically and pathologically relevant process of mitochondrial calcium homeostasis. The ubiquitous mitochondrial calcium uniporter (MCU) oligomerizes to form pores. MCU also oligomerizes with a new dominant‐negative isoform, MCUb, which blocks calcium uptake revealing a new mechanism of mitochondrial calcium homeostasis and thus aerobic metabolism and apoptosis.

Purpose To compare the number and properties of bone marrow stromal cells (BMSCs) collected from bone marrow aspirate concentrate (BMAC) obtained from different harvest sites and from patients of different ages. Methods BMAC was obtained from two groups of patients based on age ( n  = 10 per group): 19.0 ± 2.7 years for the younger and 56.8 ± 12.5 for the older group. In the latter, BMAC was obtained from both iliac crest and proximal tibia for a donor-matched analysis. Mononucleated cell count and CFU-F assay were performed, together with phenotype characterization of BMSCs from iliac crest and proximal tibia, the study of chondrogenic and osteogenic differentiation capacity, histological staining and spectrophotometric quantification, and the analysis of mRNAs expression. Results Cells derived from iliac crest and proximal tibia showed the same phenotypic pattern at flow cytometry, as well as similar chondrogenic and osteogenic potential. However, a significantly higher number of mononuclear cells per ml was observed in younger patients (3.8 ± 1.8 × 10 7 ) compared to older patients (1.2 ± 0.8 × 10 7 ) ( p  < 0.0005). The latter yield, obtained from the iliac crest, was significantly higher than resulting from the BMAC harvested from the proximal tibia in the same group of patients (0.3 ± 0.2 × 10 7 , p  < 0.0005). This result was confirmed by the CFU-F analysis at day 10 (15.9 ± 19.4 vs 0.6 ± 1.0, p  = 0.001) and day-20 (21.7 ± 23.0 vs 2.9 ± 4.2, p  = 0.006). Conclusion Harvest site and age can affect the quality of BMAC. BMSCs obtained from iliac crest and proximal tibia present comparable mesenchymal markers expression as well as osteogenic and chondrogenic differentiation potential, but iliac crest BMAC presents a four times higher number of mononucleated cells with significantly higher clonogenic capacity compared to the tibia. BMAC of younger patients also had a three-time higher number of mononucleated cells. The identification of BMAC characteristics could help to optimize its preparation and to identify the most suitable indications for this orthobiologic treatment in the clinical practice.

Indium is considered a valuable and irreplaceable material for a variety of applications that improve the quality of human life. Due to its limited availability and the growing demand, it is mandatory to find sustainable solutions for indium recovery from end-of-life devices. The green indium patented technology SCRIPT (ITA202018000008207) focuses on recovering indium from ground LCD panels, developed through laboratory scale investigation. The process ensures high recovery efficiencies of indium (>90%), features a simple design, and fully exploits the solid residue with the production of a concrete for building applications. This manuscript presents a study focused on the validation and optimization of the patented SCRIPT technology at the bench scale, driven by sustainability assessment. Bench scale experiments successfully validated the technology, improving its technology readiness level. Furthermore, an environmental sustainability assessment highlighted the importance of treating the finest fraction, which has the highest indium concentration. Optimization tests at the bench scale demonstrated that water could be recirculated for more than five cycles. The economic sustainability tests highlighted that when the indium concentration in the material fed into the recycling plant is above 1000 mg/kg, the technology is cost effective and worth investment. Our study is fundamental for boosting indium recycling in the world. Moreover, our methodological approach represents a guideline for achieving sustainability goals within circular economy approaches for strategic metals in complex matrices.

Adipose tissue-derived cell-based injectable therapies have been demonstrated to have disease-modifying effects on joint tissues in preclinical studies on animal osteoarthritis (OA) models, but clinical results are heterogeneous and not always satisfactory. The aim of this study was to investigate the influence of adipose tissue properties on the therapeutic effects of the adipose-derived product in an in vitro OA setting. Micro-fragmented adipose tissue (MF-AT) samples were obtained from 21 OA patients (mean age 51.7 ± 11.8 years, mean BMI 25.7 ± 4.1 kg/m2). The analysis of the MF-AT supernatant was performed to analyze the release of inflammatory factors. The effects of MF-AT inflammatory factors were investigated on chondrocytes and synoviocytes gene expression levels. Patients’ characteristics were analyzed to explore their influence on MF-AT inflammatory molecules and on the MF-AT effects on the gene expression of chondrocytes and synoviocytes. The study results demonstrated that adipose tissue-derived products may present inflammatory properties that influence the therapeutic potential for OA treatment, with products with a higher pro-inflammatory profile stimulating a higher expression of genes related to a more inflamed and catabolic phenotype. A higher pro-inflammatory cytokine pattern and a higher pro-inflammatory effect were found in adipose tissue-derived products obtained from OA patients with higher BMI.