Platelet-rich plasma: biological characteristics and clinical application

L’OA del ginocchio è una delle patologie degenerative articolari più diffuse che colpisce un numero crescente di persone a livello mondiale e per la quale non esiste tuttora una cura definitiva. Differenti strategie terapeutiche sistemiche e locali sono applicate nella pratica clinica, dai trattamenti farmacologici, alle procedure infiltrative. Sfortunatamente quando queste strategie terapeutiche falliscono, l’unica opzione per evitare o rimandare la sostituzione totale dell’articolazione è rappresentata da tentativi chirurgici invasivi, con tempi di riabilitazione molto lunghi e spesso incompleti e limitati nel tempo. Al fine quindi di proporre una soluzione mini-invasiva per migliorare lo stato della superficie articolare e permettere un veloce ritorno alle attività quotidiane, sono stati sviluppati approcci terapeutici di origine biologica, tra questi i concentrati piastrinici (PRP). La mancanza di PRP omogenei in letteratura rende difficile paragonare i risultati ottenuti nei vari studi complicando la ricerca, sia in campo preclinico che nella valutazione dell’efficacia di questo approccio per il trattamento di lesioni dell’apparato muscoloscheletrico nell’uomo. L’obiettivo di questo lavoro di Dottorato è quello di approfondire la conoscenza dell’effetto dei concentrati piastrinici attraverso un approccio multidisciplinare, integrando i risultati in vitro ed in vivo, integrando i risultati al fine di ottimizzare i protocolli di applicazione esistenti ed aumentare il potenziale terapeutico di questo innovativo approccio terapeutico. Il PRP è un trattamento sicuro, i dati clinici mostrano infatti l’assenza di eventi avversi post trattamento. Non può essere considerato come trattamento di prima linea per quei pazienti affetti da degenerazione della cartilagine articolare, anche da un punto di vista puramente logistico, limitando il suo impiego a pazienti che non hanno tratto beneficio da altri trattamenti conservativi. Particolare importanza rivestono la concentrazione delle piastrine, dei leucociti e il metodo di attivazione, che possono essere modulati al fine di crear il PRP idoneo al tipo di patologia da trattare.Knee OA is one of the most common degenerative joint disease that affects an increasing number of people worldwide and for which there is still no definitive cure. Different local and systemic therapeutic strategies are applied in clinical practice, as pharmacological treatments or the infiltrative procedures. Unfortunately, when these therapeutic strategies fail, the only option to avoid or postpone total joint replacement is represented by invasive surgical procedures, with very long rehabilitation times and often incomplete and limited in time. Therefore, in order to propose a mini-invasive solution to improve the status of the articular surface and allow a faster return to daily activities, therapeutic approaches of biological origin have been developed, among these platelet concentrates (PRP) are gaining great attention to the scientific community. A lack of omogeneous PRP in the literature makes it difficult to compare results across studies complicating the research, both in the field that in the preclinical evaluation of this approach for the treatment of musculoskeletal injuries apparatus in humans. The aim of this PhD work is to deepen the understanding of the effect of platelet concentrates through a multidisciplinary approach by integrating the results in vitro and in vivo in order to optimize existing application protocols and increase the potential therapeutic use of this innovative approach. The PRP is safe, clinical data show in fact the absence of adverse events after treatment. It cannot be considered as first-line treatment for patients suffering from degeneration of articular cartilage, even from a purely logistical point of view, limiting its use in patients who have not benefited from other conservative treatments. Of particular importance are the concentration of platelets, leukocytes and the activation method, which can be modulated in order to create the proper PRP for the pathology to be treated

Secretome and Extracellular Vesicles as New Biological Therapies for Knee Osteoarthritis: A Systematic Review

Secretome and extracellular vesicles (EVs) are considered a promising option to exploit mesenchymal stem cells’ (MSCs) properties to address knee osteoarthritis (OA). The aim of this systematic review was to analyze both the in vitro and in vivo literature, in order to understand the potential of secretome and EVs as a minimally invasive injective biological approach. A systematic review of the literature was performed on PubMed, Embase, and Web of Science databases up to 31 August 2019. Twenty studies were analyzed; nine in vitro, nine in vitro and in vivo, and two in vivo. The analysis showed an increasing interest in this emerging field, with overall positive findings. Promising in vitro results were documented in terms of enhanced cell proliferation, reduction of inflammation, and down-regulation of catabolic pathways while promoting anabolic processes. The positive in vitro findings were confirmed in vivo, with studies showing positive effects on cartilage, subchondral bone, and synovial tissues in both OA and osteochondral models. However, several aspects remain to be clarified, such as the different effects induced by EVs and secretome, which is the most suitable cell source and production protocol, and the identification of patients who may benefit more from this new biological approach for knee OA treatment

Exploring teachers’ perceptions of critical digital literacies and how these are manifested in their teaching practices

Digital systems are increasingly becoming central to the running of contemporary schools. A range of digital tools are also adopted by teachers to facilitate face to face teaching and learning and more recently to accommodate remote schooling. Similarly, digital technologies lie at the heart of how students support their learning but also interact with peers. These digital practices raise questions in relation to teachers’ own critical digital literacies as well as their role in developing students’ critical digital literacies. This paper presents the findings of a qualitative study that aimed to develop an understanding of teachers’ current experiences and future needs relating to critical digital literacies within school contexts. Drawing on empirical data collected during focus group interviews with primary and secondary school teachers in Finland, Italy, Spain and the UK this paper looks at teachers’ perceptions of critical digital literacies and explores whether and how these are manifested in their practices. Findings revealed that different dimensions of critical digital literacies were more prevalent for each national group and highlighted the disjuncture between how Critical digital literacies (CDL) is defined and perceived in academic research with a stronger emphasis on the “critical” and between the more “twenty-first century skills” oriented policy agendas and curricula which inform teachers’ practice. The paper goes on to discuss the implications of these findings and identifies gaps in relation to teachers’ understandings of critical digital literacies. Last, it offers original insights for future policymaking, research and practice regarding the challenges of supporting teachers with developing critical digital literacies

“SOLET”, a self-organised learning environment for teachers about critical digital literacies : proposal and validation

Although digital technologies have generated innumerable opportunities to develop skills for future social, cultural and economic scenarios, their use is nowadays generating several concerns. Decades of research on the adoption of educational technologies have led to understanding that “techno-enthusiasm” might only lead to dead ends in the best of scenarios. In the worst of cases, and particularly in the COVID19 aftermath, several issues associated with the lack of ergonomics at home and technology overexposure, dependence, and burnout have been discussed in the light of critically reconsidering technology-enhanced pedagogies. Such a situation requires not only careful educational research and policymaking, but particularly, a change in the direction of teachers’ professional development. In this context, the EU Erasmus+ Project DETECT (https://www.detectproject.eu/) is a transnational effort aimed to raise awareness amongst educators and support them in understanding the critical digital literacies scenarios and requirements. The project started in 2019 and has already developed a framework including eight areas of critical digital literacy and has been validated. This paper aims at enhancing such a framework by offering the teachers activities and resources to develop their professional skills to implement critical digital literacies at school. Such a professional learning offer is denominated “SOLET” (Self-Organised Learning Environment for Teachers) and its aim is to promote problem-based activities addressing the integration of conceptual reflection with design-thinking. The ultimate goal is to prepare teachers to design for learning around several scenarios and cases requiring critical technology appraisal and usage. The course is based on heutagogy, offering resources and cases to interact with. Moreover, taking into account the concept of “comparators” developed by Nicol the learning architecture embraces automatic, self and peer-assessment as specific activities providing sources of comparison for the participants’ reflection on their own learning. Through this approach, it is expected to ease teachers' access to professional learning opportunities, with implications for the transference of complex concepts like the eight areas of the framework to practice. Ultimately, it is expected to support teachers with enhancing their own students’ opportunities to develop critical digital literacies. The SOLET environment is under development and two rounds of user testing have been already undertaken. The first has included 8 researchers from four universities and one training institution, collecting 161 reviews. The interrater agreement was calculated over the basis of double-blind evaluation of a sample of interactions, yielding a reasonable agreement (83.33%) on the type of technological and interaction issues requiring improvement. The second user test was carried out by five teachers in two collaborative sessions; 18 reviews were collected, yielding more concerns (75% of agreement) but convergence in the adjustments was apparent. These results are discussed in the light of the research relating to teachers’ self-paced professional learning. Finally, the presentation in the conference context might encompass a unique opportunity to collect feedback.Peer reviewe

Effect of two different preparations of platelet-rich plasma on synoviocytes

To analyse the modifications induced by two different platelet-rich plasma (PRP) preparations on osteoarthritis (OA) synoviocytes, by documenting changes in gene expression of factors involved in joint physiopathology.OA synoviocytes were cultured for 7 days in medium with different concentrations of either P-PRP (a pure platelet concentrate without leucocytes but with a limited number of platelets), L-PRP (a higher platelet concentrate containing leucocytes) or platelet-poor plasma (PPP). Gene expression of interleukin (IL)-1beta, IL-6, IL-8/CXCL8, tumour necrosis factor alpha, IL-10, IL-4, IL-13, metalloproteinase-13, tissue inhibitor of metalloproteinase (TIMP)-1, (TIMP)-3, (TIMP)-4, vascular endothelial growth factor, transforming growth factor beta1, fibroblast growth factor (FGF)-2, hepatocyte growth factor (HGF), hyaluronic acid (HA) synthases (HAS)-1, (HAS)-2, and (HAS)-3 was analysed by RT-PCR. HA production was determined in culture supernatants by ELISA.IL-1β, IL-8 and FGF-2 were significantly induced by L-PRP compared to both P-PRP and PPP; HGF was down-modulated by L-PRP versus both P-PRP and PPP, and an inverse dose-response influence was shown for all preparations. Expression level of TIMP-4 was lower in the presence of L-PRP compared with P-PRP. HA production and HAS gene expression did not seem to be modulated by PRP.L-PRP is able to sustain the up-regulation of proinflammatory factors, (IL-1beta, IL-8 and FGF-2), together with a down-modulation of HGF and TIMP-4 expression, two factors that have been recognized as anti-catabolic mediators in cartilage, thus supporting the need to further optimize the PRP preparations to be applied in clinical practice

Release kinetic of pro- and anti-inflammatory biomolecules from platelet-rich plasma and functional study on osteoarthritis synovial fibroblasts

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Il sistema endocannabinoico nella depressione e nel suicidio

Il sistema endocannabinoico nella depressione e nel suicidi