bluuebunny/crossref_metadata_2025 huggingface dataset:
ZNACZENIE OSOBY W MISTERIUM CHRYSTUSA I KOŚCIOŁA WOBEC IDEOLOGII W UJĘCIU JOSEPHA RATZINGERA – BENEDYKTA XVI
Authors: Gacka Bogumił
Published: January 2024

Według J. Ratzingera-Benedykta XVI hermeneutycznym ośrodkiem Pisma Świętego, ukazującego zbawczą historię Boga z ludźmi, jest misterium Chrystusa i Kościoła (Christus et Ecclesia, por. św. Augustyn). Wzajemną więź stanowi relacja Miłości, czyli relacja osobowa. Wiara chrześcijańska nie odnosi się bowiem do idei, tylko do Osoby. U początku bycia chrześcijaninem jest spotkanie z Osobą Chrystusa. Jezus to imię Boga, które znaczy „Bóg zbawia”. J. Ratzinger dostrzegł dwa okresy w kształtowaniu się pojęcia osoby w teologii: (1) przejście od substancji do subsystencji (hipostazy), (2) przejście od subsystencji do relacji, zatem osoba to nie tylko samoistność, ale samoistność relacyjna, subsystencja relacyjna (relatio subsistens). Osoba ludzka jest jednością ciała i duszy, corpore et anima unus (KDK, 14). Według J. Ratzingera–Benedykta XVI stworzenie człowieka na obraz i podobieństwo Boga oznacza, że osoba ludzka jako subsystencja w relacji jest ukonstytuowana w relacji do Boga i bliźnich. Obraz Boga wyraża nie tylko rozumność i wolność, co dotychczas podkreślano, ale podobieństwo do Boga Osobowego (Communio Personarum) oznacza, że odniesienie do Boga i odniesienie do bliźniego konstytuują osobę ludzką, stanowią jej strukturę konstytutywną jako istoty relacyjnej (communio personarum). To oznacza, że osoba ludzka bez relacji do Boga i bliźniego nie może żyć. Miłuj Boga i bliźniego, to czyń, a będziesz żył! (por. Łk 10, 27–28). Podobnie jak Jan Paweł II, Benedykt XVI uważał, że autentyczna demokracja możliwa jest tylko w państwie prawnym i w oparciu o poprawną koncepcję osoby ludzkiej. Nie będąc ideologią, wiara chrześcijańska nie sądzi, by mogła ująć w sztywny schemat różnorodną rzeczywistość społeczno-polityczną i uznaje, że życie ludzkie w historii realizuje się na różne sposoby, które bynajmniej nie są doskonałe (Centesimus annus, 46). Ideologie odnoszą się do idei i posługują się osobami dla osiągnięcia celu. Ojcowie Kościoła widzieli rozstrzygające znaczenie przyjścia Osoby Jezusa Chrystusa, Syna Ojca, który stał się Człowiekiem. Zatem relacja z Osobą Jezusa chroni nas od wszelkich ideologii. Do pomagania człowiekowi w podejmowaniu tej relacji ustanowiony jest Kościół jako Oblubienica Baranka.
PARADYGMAT MARIOLOGII OBIEKTYWNEJ. CZY JEST JESZCZE MOŻLIWA TEOLOGICZNA SYNTEZA?
Authors: Kunka Sławomir
Published: January 2024

Dogmat Niepokalanego Poczęcia Matki Bożej, jako „doktrynalna synteza wiary chrześcijańskiej” (św. Jan Paweł II), mógłby posłużyć jako ognisko skupiające różne koncepcje i ujęcia teologiczne dotyczące historii zbawienia. Aby jednak tak mogło się stać, potrzeba pogłębienia i odkrycia bogactwa samej mariologii. Często bowiem traktowana jako dziedzina poboczna, jako kontekst dla innych dziedzin czy nawet źródło trudności w dialogu ekumenicznym, potrzebuje dziś swoistej odnowy. Postulat konstruowania tzw. mariologii obiektywnej zakłada zachowanie autonomii teologii jako nauki, obiektywizację merytoryczną i formalną w teologicznej refleksji o Maryi. Aby spełnić te postulaty, należy ubiegać się o uszanowanie nadprzyrodzonej celowości oraz źródeł teologii jako takiej, umacniać i rozwijać mariologię biblijną oraz refleksję ojców Kościoła. Potrzeba także czerpania z bogactwa szkoły franciszkańskiej w refleksji nad jednością planu stworzenia i Odkupienia w odwiecznych zamysłach Boga. Wreszcie nie można zgodzić się na zerwanie „hermeneutyki ciągłości” katolickiej nauki o Najświętszej Maryi Pannie, Matce Boga, Niepokalanej i Wniebowziętej. Artykuł stara się omówić istotę powyższych postulatów oraz proponuje konkretne warunki dla umożliwienia rozwoju tzw. mariologii obiektywnej. Ważnym jej elementem jest wyjście od Pierwszej Osoby Trójcy Świętej w refleksji nad planem zbawienia, którego Niepokalane Poczęcie jest alfalnym i omegalnym elementem.
EDUKACYJNY, WYCHOWAWCZY I DUCHOWY CHARAKTER PISM MAGDALENY MORTĘSKIEJ (1554-1631)
Authors: Kurasz Katarzyna
Published: January 2024

Magdalena Mortęska żyła w latach 1554–1631. Mimo sprzeciwu ojca w grudniu 1578 r. wstąpiła do klasztoru benedyktynek w Chełmnie, a 4 czerwca 1579 r. złożyła śluby zakonne. Następnie została wybrana ksienią chełmińskiego konwentu. Była postacią nieprzeciętną o wielkich zdolnościach umysłu i niezwykłej duchowości. Podjęta przez nią reforma objęła łącznie 22 klasztory na terenie całej Rzeczypospolitej. Nowe fundacje powodowały napływ coraz większej liczby nowicjuszek. Przy każdym klasztorze ksieni chełmińska zakładała szkoły dla dziewcząt. Przyczyniła się w ten sposób do szerzenia kultury i oświaty wśród kobiet. Magdalena Mortęska pozostawiła po sobie spuściznę w postaci listów, spisanych wygłoszonych przez nią nauk oraz rozmów z mniszkami. Jest również autorką dzieła Rozmyślania o Męce Pańskiej. Celem artykułu jest ukazanie wybitności Magdaleny Mortęskiej oraz przeanalizowanie pism jej autorstwa pod kątem edukacyjnym, wychowawczym i duchowym.
RĘKOPISY I WYDANIA TEKSTU GRECKIEGO STAREGO TESTAMENTU
Authors: Parchem Marek
Published: January 2024

Niniejszy artykuł zawiera zaktualizowaną przez badaczy listę świadków tekstu Septuaginty, czyli greckich rękopisów powstałych na przestrzeni wieków (papirusy, uncjały, minuskuły), lekcjonarzy oraz cytatów Ojców Kościoła i innych starożytnych pisarzy. Druga część artykułu skupia się na drukowanych wydaniach Biblii Greckiej.
Ks. prof. dr hab. Czesław Rychlicki (1939-2022). Życie i działalność naukowo-dydaktyczna
Authors: Brzeziński Daniel
Published: January 2024

W opracowaniu przypomniano sylwetkę oraz działalność naukowo-dydaktyczną ks. prałata prof. Czesława Rychlickiego (1939–2022), emerytowanego profesora Wydziału Teologicznego Uniwersytetu Mikołaja Kopernika w Toruniu. Zmarły 17 grudnia 2022 r. prezbiter Diecezji Płockiej był znanym i cenionym – nie tylko w Polsce – uczonym i nauczycielem akademickim, wychowawcą wielu pokoleń kapłanów i osób świeckich, organizatorem życia naukowego oraz popularyzatorem nauki i promotorem nowych kadr naukowych. Przedstawione w artykule curriculum vitae i zaprezentowane kierunki naukowych poszukiwań oraz praca wychowawczo-organizacyjna ks. prof. Czesława Rychlickiego pozwalają na uświadomienie sobie ich zasięgu, różnorodności, znaczenia i bogactwa. Mogą również stać się przyczynkiem do kompleksowych i pogłębionych badań nad pozostawioną przez niego spuścizną duchową i intelektualną.
Małe wspólnoty religijne w służbie misji ewangelizacyjnej Kościoła
Authors: Zarembski Zbigniew
Published: January 2024

Istnienie małych grup w Kościele nie jest zjawiskiem nowym. Od wieków działały w nim bractwa, sodalicje, stowarzyszenia i towarzystwa. Po Soborze Watykańskim II nastąpił gwałtowny rozwój nowych grup, ruchów i wspólnot religijnych. Spowodowany on był soborową odnową eklezjologii, działaniem Ducha Świętego jak również promocją laikatu oraz dążeniem ludzi świeckich do zrzeszania się. Jednocześnie obecność małych wspólnot religijnych doskonale wpisuje się w misję ewangelizacyjną Kościoła, który powołany został do głoszenia Dobrej Nowiny. Zadanie to spoczywa na całym Ludzie Bożym, a więc hierarchii i świeckich. Przyjęty sakrament chrztu świętego zobowiązuje wszystkich ochrzczonych do zaangażowania się w dzieło ewangelizacji, głoszenia Chrystusa słowem i życiem. W niniejszym artykule przedstawiono w trzech odsłonach znaczenie i wkład małych wspólnot religijnych w służbie misji ewangelizacyjnej Kościoła.
Editorial. Los desafíos del periodismo narrativo
Authors: Amado Suárez Adriana , Seoane Pérez Francisco
Published: January 2024

Editorial del número 14(1) de enero-junio de 2021.
Acontecer y comunicación. Una historia del periodismo
Authors: Acosta Meneses María Yanet
Published: January 2024

Reseña del libro Acontecer y comunicación. Una historia del periodismo
PROPOSTA DE ATIVIDADE DE LEITURA E ESCRITA DE PORTUGUÊS PARA ALUNOS SURDOS DO ENSINO MÉDIO POR MEIO DO GÊNERO DISCURSIVO BIOGRAFIA DO INSTAGRAM / PROPOSAL FOR A PORTUGUESE READING AND WRITING ACTIVITY FOR DEAF HIGH SCHOOL STUDENTS USING THE DISCURSIVE GENRE INSTAGRAM BIOGRAPHY
Authors: Silva Karolina da Cruz , Abreu Walber Gonçalves de , Barros Oclícia Sales , Cruz Regina Célia Fernandes
Published: January 2024

Atualmente, a legislação brasileira assegura o direito à educação das pessoas surdas a partir de diversos dispositivos legais. Contudo, a realidade revela uma parcela considerável de alunos surdos que têm privado seu direito a uma educação linguageira para desenvolver competência na língua de sinais e na língua portuguesa. Uma das dificuldades se dá pela falta de conhecimento por parte do corpo escolar de metodologias que assegurem ao aluno surdo a possibilidade de aprender a língua portuguesa. Diante disso, o objetivo da pesquisa é apresentar uma proposta de atividade para o ensino de português para alunos surdos do ensino médio de uma escola pública do município de Santa Izabel do Pará/PA, por meio do gênero discurso biografia do Instagram. Para isso, foram trazidos à cena discussões acerca do bilinguismo para surdos (SALLES et al., 2004 e QUADROS, 2008) e do gênero discursivo e multiletramento (BAKHTIN, 2003 e ROJO, 2012). A proposta de atividade foi aplicada em uma sala de AEE com três alunos surdos. Adotamos uma sequência didática que considera as etapas estudo do gênero, vocabulário visuo-verbal, aspectos gramaticais e produção (CARDOSO-JUNIOR, 2018 e ABREU, 2019). Como resultados, apontamos que os discentes conseguiram produzir suas biografias do instagram considerando as características estruturais e funcionais do gênero, além de aplicar adequadamente o vocabulário e os verbos e adjetivos que são necessários para a elaboração desse tipo de texto. Além disso, os discentes fizeram uma associação coerente entre texto verbal e emojis, recurso muito utilizado nas redes sociais.
Managing the inappetent hospitalised cat: International Society of Feline Medicine guidelines
Authors: Taylor Samantha
Published: January 2024

Inappetence (also called hyporexia or anorexia) is a common presenting symptom in cats, but suboptimal nutrition can have many negative effects on feline patients, including prolonged hospitalisation and shortened survival. Cats are strict carnivores with a high protein requirement, and when starvation is combined with the hypermetabolic state found in sick cats, a loss of lean body mass can occur. This can have negative effects on wound healing, immune function and gut function. Inappetence in hospitalised cats is not just caused by the underlying illness; it can be exacerbated by stress, as well as factors such as pain, nausea, ileus, constipation and the adverse effects of medication. All contributing factors should be managed, along with the primary disease process, to correct malnutrition. Nutritional assessment of each hospitalised cat allows the identification of patients who require prompt intervention. Appetite stimulants can encourage voluntary food intake and feeding tubes allow provision of nutrition, fluids and medications, and can be managed at home to expedite discharge. The food intake of hospitalised cats should be closely monitored and inappetence should not be ignored, nor intervention delayed.
Addison's disease caused by adrenal tuberculosis may lead to misdiagnosis of major depressive disorder: A case report
Authors: Zhang Tian-Xiang , Xu Hong-Yan , Ma Wei , Zheng Jian-Bao
Published: January 2024

BACKGROUND

Addison’s disease (AD) is a rare but potentially fatal disease in Western countries, which can easily be misdiagnosed at an early stage. Severe adrenal tuberculosis (TB) may lead to depression in patients.

CASE SUMMARY

We report a case of primary adrenal insufficiency secondary to adrenal TB with TB in the lungs and skin in a 48-year-old woman. The patient was misdiagnosed with depression because of her depressed mood. She had hyperpigmentation of the skin, nails, mouth, and lips. The final diagnosis was adrenal TB that resulted in the insufficient secretion of adrenocortical hormone. Adrenocortical hormone test, skin biopsy, T cell spot test of TB, and adrenal computed tomography scan were used to confirm the diagnosis. The patient’s condition improved after hormone replacement therapy and TB treatment.

CONCLUSION

Given the current status of TB in high-burden countries, outpatient doctors should be aware of and pay attention to TB and understand the early symptoms of AD.
FROM NOVEL COATING STRATEGY ON BIODEGRADABLE MG-BASED ORTHOPAEDIC IMPLANT MATERIAL TOWARDS CLINICAL TRIAL
Authors: Li R.W. , Zheng J. , Smith P.N. , Chen X.
Published: January 2024

Device-associated bacterial infections are a major and costly clinical challenge. This project aimed to develop a smart new biomaterial for implants that helps to protect against infection and inflammation, promote bone growth, and is biodegradable. Gallium (Ga) doped strontium-phosphate was coated on pure Magnesium (Mg) through a chemical conversion process. Mg was distributed in a graduated manner throughout the strontium-phosphate coating GaSrPO4, with a compact structure and a Ga-rich surface. We tested this sample for its biocompatibility, effects on bone remodeling and antibacterial activities including Staphylococcus aureus, S. epidermidis and E. coli - key strains causing infection and early failure of the surgical implantations in orthopaedics and trauma.

Ga was distributed in a gradient way throughout the entire strontium-phosphate coating with a compact structure and a gallium-rich surface. The GaSrPO4 coating protected the underlying Mg from substantial degradation in minimal essential media at physiological conditions over 9 days. The liberated Ga ions from the coatings upon Mg specimens inhibited the growth of bacterial tested. The Ga dopants showed minimal interferences with the SrPO4 based coating, which boosted osteoblasts and undermined osteoclasts in in vitro co-cultures model.

The results evidenced this new material may be further translated to preclinical trial in large animal model and towards clinical trial.

Acknowledgements: Authors are grateful to the financial support from the Australian Research Council through the Linkage Scheme (ARC LP150100343). The authors acknowledge the facilities, and the scientific and technical assistance of the RMIT University and John Curtin School of Medical Research, Australian National University.
IS TOTAL HIP ARTHROPLASTY FIXATION ASSOCIATED WITH OSTEOBLAST ACTIVITY IN PATIENTS WITH OSTEONECROSIS OF THE FEMORAL HEAD? A PROSPECTIVE CASE-CONTROL STUDY
Authors: García-Rey E. , Pérez-Barragans F. , Saldaña L.
Published: January 2024

Total hip arthroplasty (THA) outcome in patients with osteonecrosis of the femoral head ONFH) are excellent, however, there is controversy when compared with those in patients with osteoarthritis (OA). Reduced mineralization capacity of osteoblasts of the proximal femur in patients with ONFH could affect implant fixation.

We asked if THA fixation in patients with ONFH is worse than in those with OA.

We carried out a prospective comparative case (OA)-control (ONFH) study of patients undergoing THA at our hospital between 2017 and 2019. The minimum follow-up was 2 years. Inclusion criteria were patients with uncemented THA, younger than 70 years old, a Dorr femoral type C and idiopathic ONFH. We compared the clinical (Merlé D'Aubigné-Postel score) and radiological results related with implant positioning and fixation. Engh criteria and subsidence were assessed at the immediate postoperative, 12 weeks, 6 months, 12 months and yearly. Osteoblastic activity was determined by mineralization assay on primary cultures of osteoblasts isolated from trabecular bone samples collected from the intertrochanteric area obtained during surgery.

Group 1 (ONFH) included 18 patients and group 2 (OA), 22. Average age was 55.9 years old in group 1 and 61.3 in group 2. (p=0.08). There were no differences related with sex, Dorr femoral type or femoral filling. The mean clinical outcome score was 17.1 in group 1 and 16.5 in group 2 (p=0.03). There were no cases of dislocation, infection, or revision surgery in this series. There were 5 cases (28%) of femoral stem subsidence greater than 3mm within 6 first months in group 1 and 1 case (4.5%) in group 2 (p=0.05).

Although there were no significant differences related to clinical results, bone fixation was slower, and a greater subsidence was observed in patients with ONFH. Greater femoral stem subsidence was associated with a lower capacity for mineral nodule formation in cultured osteoblasts. The surgical technique could influence THA outcome in patients with reduced mineralization capacity of osteoblasts.
A NOVEL BIOMIMETIC BONE ADHESIVE: TRANSLATION FROM SMALL TO LARGE ANIMAL PRECLINICAL MODEL ON THE PATH TO FIRST IN-HUMAN USE
Authors: Procter P. , Hulsart-Billström G. , Alves A. , Pujari-Palmer M. , Wenner D. , Insley G. , Engqvist H. , Larsson S. , Pippenger B. , Bossard D.
Published: January 2024

Surgeons treating fractures with many small osteochondral fragments have often expressed the clinical need for an adhesive to join such fragments, as an adjunct to standard implants. If an adhesive would maintain alignment of the articular surfaces and subsequently heal it could result in improved clinical outcomes. However, there are no bone adhesives available for clinical indications and few pre-clinical models to assess safety and efficacy of adhesive biomaterial candidates. A bone adhesive candidate based on water, α-TCP and an amino acid phosphoserine was evaluated in-vivo in a novel murine bone core model (preliminary results presented EORS 2019) in which excised bone cores were glued back in place and harvested @ 0, 3, 7, 14, 28 and 42days. Adhesive pull-out strength was demonstrated 0–28 days, with a dip at 14 days increasing to 11.3N maximum. Histology 0–42 days showed the adhesive progressively remodelling to bone in both cancellous and cortical compartments with no signs of either undesirable inflammation or peripheral ectopic bone formation. These favourable results suggested translation to a large animal model.

A porcine dental extraction socket model was subsequently developed where dental implants were affixed only with the adhesive. Biomechanical data was collected @ 1, 14, 28 and 56 days, and histology at 1,14,28 and 56 days. Adhesive strength assessed by implant pull-out force increased out to 28 days and maintained out to 56 days (282N maximum) with failure only occurring at the adhesive bone interface. Histology confirmed the adhesive's biocompatibility and osteoconductive behavior. Additionally, remodelling was demonstrated at the adhesive-bone interface with resorption by osteoclast-like cells and followed by new bone apposition and substitution by bone. Whilst the in-vivo dental implant data is encouraging, a large animal preclinical model is needed (under development) to confirm the adhesive is capable of healing, for example, loaded osteochondral bone fragments.

Acknowledgements: The murine study was supported, in part, by the Swedish Foundation for Strategic Research (#RMA15-0110).
ADVANCED TENDON REPAIR STRATEGIES: FROM EVS TO MRNA-BASED APPROACHES
Authors: Traweger Andreas
Published: January 2024

Approximately 30% of general practice consultations for musculoskeletal pain are related to tendon disorders, causing substantial personal suffering and enormous related healthcare costs. Treatments are often prone to long rehabilitation times, incomplete functional recovery, and secondary complications following surgical repair. Overall, due to their hypocellular and hypovascular nature, the regenerative capacity of tendons is very poor and intrinsically a disorganized scar tissue with inferior biomechanical properties forms after injury. Therefore, advanced therapeutic modalities need to be developed to enable functional tissue regeneration within a degenerative environment, moving beyond pure mechanical repair and overcoming the natural biological limits of tendon healing.

Our recent studies have focused on developing biologically augmented treatment strategies for tendon injuries, aiming at restoring a physiological microenvironment and boosting endogenous tissue repair. Along these lines, we have demonstrated that the local application of mesenchymal stromal cell-derived small extracellular vesicles (sEVs) has the potential to improve rotator cuff tendon repair by modulating local inflammation and reduce fibrotic scarring. In another approach, we investigated if the local delivery of the tendon ECM protein SPARC, which we previously demonstrated to be essential for tendon maturation and tissue homeostasis, has the potential to enhance tendon healing. Finally, I will present results demonstrating the utility of nanoparticle-delivered, chemically modified mRNAs (cmRNA) to improve tendon repair.
EXTRACELLULAR VESICLES FROM TIE2-OVEREXPRESSING NUCLEUS PULPOSUS PROGENITORS FOR INTERVERTEBRAL DISC REGENERATION: AN IN VITRO STUDY
Authors: Ambrosio L. , Schol J. , Vadalà G. , Papalia R. , Sakai D. , Denaro V.
Published: January 2024

Despite promising results in attempting intervertebral disc regeneration, intradiscal cell transplantation is affected by several drawbacks, including poor viability in the harsh disc environment, low cost-effectiveness, and immunogenic/tumorigenic concerns. Recently, the development of cell-free approaches is gaining increasing interest in the field, with a particular regard towards extracellular vesicles (EVs). Nucleus pulposus cell (NPC) progenitors characterized by Tie2 expression have shown a higher chondrogenic differentiation potential compared to MSCs. The aim of this study was to investigate the putative regenerative effects of EVs isolated from Tie2-overexpressing NPC progenitors on degenerative NPCs.

NPCs were isolated from young donors and underwent an optimized culture protocol to maximize Tie2 expression (NPCsTie2+) or a standard protocol (NPCsSTD). Following EV characterization, NPC isolated from patients affected by intervertebral disc degeneration (IDD) were treated with either NPCsTie2+-EVs or NPCsSTD-EVs. Cell proliferation and viability were assessed with the CCK-8 assay. Cell apoptosis and necrosis were evaluated with the Annexin V/PI assay. Cell senescence was investigated with b-galactosidase staining. EV uptake was assessed with PKH26 staining of EVs under confocal microscopy.

Treatment with EVs isolated from young NPC donors significantly increased degenerative NPC viability, especially in samples treated with NPCsTie2+-EVs. Likewise, NPCsTie2+-EVs significantly reduced cell senescence and did not show to exert necrotic nor apoptotic effects on recipient cells. Furthermore, EV uptake was successfully observed in all treated cells.

NPCsTie2+-EVs demonstrated to significantly enhance degenerative NPC viability, senescence and apoptosis. The use of committed progenitors naturally residing the in the nucleus pulposus may optimize EV regenerative properties and constitute the basis for a new therapy for IDD.
EFFECT OF EXTRACELLULAR VESICLES DERIVED FROM HUMAN MACROPHAGES ON OSTEOSARCOMA CELLS
Authors: Bagur-Cardona S. , Perez-Romero K. , Stiliyanov K. , Calvo J. , Gayà A. , Barceló-Coblijn G. , Rodriguez R. M. , Gomez-Florit M.
Published: January 2024

Macrophages (Mφ) are immune cells that play a crucial role in both innate and adaptive immunity as they are involved in a wide range of physiological and pathological processes. Depending on the microenvironment and signals present, Mφ can polarize into either M1 or M2 phenotypes, with M1 macrophages exhibiting pro-inflammatory and cytotoxic effects, while M2 macrophages having immunosuppressive and tissue repair properties. Macrophages have been shown to play key roles in the development and progression or inhibition of various diseases, including cancer. For example, macrophages can stimulate tumor progression by promoting immunosuppression, angiogenesis, invasion, and metastasis. This work aimed to investigate the effect of extracellular vesicles (EVs)-derived from polarized macrophages on an osteosarcoma cell line. Monocytes were extracted from buffy coats and cultured in RPMI medium with platelet lysate or M-CSF. After 6 days of seeding, Mφ were differentiated into M1 and M2 with INF-γ/LPS and IL-4/IL-13, respectively. The medium with M1 or M2 derived EVs was collected and EVs were isolated by differential centrifugation and size exclusion chromatography and its morphology and size were characterized with SEM and NTA, respectively. The presence of typical EVs markers (CD9, CD63) was assessed by Western Blot. Finally, EVs from M1 or M2-polarized Mφ were added onto osteosarcoma cell cultures and their effect on cell viability and cell cycle, proliferation, and gene expression was assessed. The EVs showed the typical shape, size and surface markers of EVs. Overall, we observed that osteosarcoma cells responded differentially to EVs isolated from the M1 and M2-polarized Mφ. In summary, the use of Mφ-derived EVs for the treatment of osteosarcoma and other cancers deserves further study as it could benefit from interesting traits of EVs such as low immunogenicity, nontoxicity, and ability to pass through tissue barriers.

Acknowledgements: Carlos III Health Institute and the European Social Fund for contract CP21/00136 and project PI22/01686.
APPLICATION OF SILVER NANOPARTICLES FOR IMPROVING MOTOR RECOVERY AFTER SPINAL CORD INJURY VIA REDUCTION OF PRO-INFLAMMATORY M1 MACROPHAGES
Authors: Lin J. , Chen P.K. , Tan Z. J. , Sun Y. , Tam W.K. , Ao D. , Shen W. , Leung V. , Cheung K. M. C. , To M.K.T.
Published: January 2024

Silver nanoparticles (AgNPs) possess anti-inflammatory activities and have been widely deployed for promoting tissue repair. Here we explored the efficacy of AgNPs on functional recovery after spinal cord injury (SCI). Our data indicated that, in a SCI rat model, local AgNPs delivery could significantly recover locomotor function and exert neuroprotection through reducing of pro-inflammatory M1 survival. Furthermore, in comparison with Raw 264.7-derived M0 and M2, a higher level of AgNPs uptake and more pronounced cytotoxicity were detected in M1. RNA-seq analysis revealed the apoptotic genes in M1 were upregulated by AgNPs, whereas in M0 and M2, pro-apoptotic genes were downregulated and PI3k-Akt pathway signaling pathway was upregulated. Moreover, AgNPs treatment preferentially reduced cell viability of human monocyte-derived M1 comparing to M2, supporting its effect on M1 in human. Overall, our findings reveal AgNPs could suppress M1 activity and imply its therapeutic potential in promoting post-SCI motor recovery.
NOVEL CB65-LOADED LIPOSOME FORMULATION AS A CHEMOTHERAPEUTIC CANDIDATE FOR OSTEOSARCOMA
Authors: Zorba B.I. , Boyacioğlu Ö. , Çağlayan T. , Reçber T. , Eroğlu İ. , Nemutlu E. , Korkusuz P.
Published: January 2024

Osteosarcoma is common in children and adolescents with high mortality due to rapid progression. Therapeutic approaches for osteosarcoma are limited and may cause side effects. Cannabinoid ligands exert antiproliferative, apoptotic effect in cancer cells via CB1/2 or TRPV1 receptors. In this study, we hypothesized that synthetic specific CB2R agonist CB65 might have an antiproliferative and apoptotic effect on osteosarcoma cell lines in vitro. If so, this agent might be a chemotherapeutic candidate for osteosarcoma, with prolonged release, increased stability and bioavailability when loaded into a liposomal system. We first determined CB2 receptor expression in MG63 and Saos-2 osteosarcoma cells by qRT- PCR and FCM. CB65 reduced proliferation in osteosarcoma cells by WST-1 and RTCA. IC50 for MG63 and Saos-2 cells were calculated as 1.11×10-11 and 4.95×10-11 M, respectively. The antiproliferative effect of CB65 on osteosarcoma cells was inhibited by CB2 antagonist AM630. IC50 of CB65 induced late apoptosis of MG63 and Saos-2 cells at 24 and 48 hours, respectively by FCM. CB65 was loaded into the liposomal system by thin film hydration method and particle size, polydispersity index, and zeta potentials were 141.7±0.6 nm, 0.451±0.026, and -10.9±0.3 mV, respectively. The CB65-loaded liposomal formulation reduced MG63 and Saos-2 cell proliferation by RTCA. IC50 of CB65 and CB65-loaded liposomal formulation induced late apoptosis of MG63 and Saos-2 cells at 24 and 48 hours, respectively, by FCM. Scratch width was higher in CB65 and CB65-loaded liposome-treated cells compared to control. In this study, the real-time antiproliferative and apoptotic effect of synthetic specific CB2 agonist CB65 in osteosarcoma cell lines was demonstrated for the first time, and the real time therapeutic window was determined. The CB65-loaded liposomal formulation presents a potential treatment option that can be translated to clinic following its validation within animal models and production under GMP conditions.
NOVEL ANTIMICROBIAL COATING ON TITANIUM WITH STABLE NON-ANTIBIOTIC QUATERNARY AMMONIUM COMPOUNDS TO PREVENT IMPLANT-ASSOCIATED INFECTION
Authors: Riool M. , Li R. , Hofwegen L.v. , de Boer L. , Loontjens J.A. , Zaat S.A.J.
Published: January 2024

Infection of implanted medical devices (biomaterials), like titanium orthopaedic implants, can have disastrous consequences, including removal of the device. These so-called biomaterial-associated infections (BAI) are mainly caused by Staphylococcus aureus and Staphylococcus epidermidis. To prevent biofilm formation using a non-antibiotic based strategy, we aimed to develop a novel permanently fixed antimicrobial coating for titanium devices based on stable immobilized quaternary ammonium compounds (QACs).

Medical grade titanium implants were dip-coated in subsequent solutions of hyperbranched polymer, polyethyleneimine and 10 mM sodium iodide, and ethanol. The QAC-coating was characterized using water contact angle measurements, scanning electron microscopy, FTIR, AFM and XPS. The antimicrobial activity of the coating was evaluated against S. aureus strain JAR060131 and S. epidermidis strain ATCC 12228 using the JIS Z 2801:2000 surface microbicidal assay. Lastly, we assessed the in vivo antimicrobial activity in a mouse subcutaneous implant infection model with S. aureus administered locally on the QAC-coated implants prior to implantation to mimic contamination during surgery.

Detailed material characterization of the titanium samples showed the presence of a homogenous and stable coating layer at the titanium surface. Moreover, the coating successfully killed S. aureus and S. epidermidis in vitro. The QAC-coating strongly reduced S. aureus colonization of the implant surface as well as of the surrounding tissue, with no apparent macroscopic signs of toxicity or inflammation in the peri-implant tissue at 1 and 4 days after implantation.

An antimicrobial coating with stable quaternary ammonium compounds on titanium has been developed which holds promise to prevent BAI. Non-antibiotic-based antimicrobial coatings have great significance in guiding the design of novel antimicrobial coatings in the present, post-antibiotic era.

Acknowledgements: This research was financially supported by the Health∼Holland/LSH-TKI call 2021–2022, project 25687, NACQAC: ‘Novel antimicrobial coatings with stable non-antibiotic Quaternary Ammonium Compounds and photosensitizer technology'.
CAN KINETICS AND KINEMATICS OF SINGLE LEG FORWARD AND CROSSOVER TRIPLE HOP TESTS DETERMINE RECREATIONAL MALE ATHLETES' RETURN TO SPORTS AFTER ACL RECONSTRUCTION?
Authors: İlicepinar Ö.F. , Imir M. , Cengiz B.C. , Gürses S. , Menderes Y. , Turhan E. , Dönmez G. , Korkusuz F.
Published: January 2024

Hop tests are used to determine return to sports after ACL reconstruction. They mostly measure distance and symmetry but do not assess kinematics and kinetics. Recently, biomechanical evaluations have been incorporated into these functional jump tests for the better assessment of return to sport. We assessed the sagittal plane range of motion (ROM) of the knee, the deviation axis of rotation (DAOR), and the vertical ground reaction force (vGRF) normalized to body weight in nine healthy participants during the single leg (SLH) and crossover hop tests (COHT).

Participants' leg lengths were measured. Jumping distances were marked in the test area as being 4/5 of the leg length. Four sensors were placed on the thighs, the legs and the feet. These body parts were handled as a single rigid body. Eight 480 Hz cameras were used to capture the movements of these rigid bodies. vGRF at landing were measured using a force plate (Bertec, Inc, USA). The ROM of the knee joint and the DAOR were obtained from kinematic data.

Participants' joint kinematics metrics were similar in within-subjects statistical tests for SLH and COHT. We therefore asked whether the repeated vGRF normalized to body weight will be similar in both legs during these jumps. Joint kinematics metrics however were different in between subjects indicating the existence of a personalized jumping strategy. These hop tests can be recorded at the beginning of the training season for each individual, which can establish a comparative evaluation database for prospective lower extremity injury recovery and return to sport after ACL injury.
AGE-RELATED MECHANISMS OF ALTERED TENDON STRUCTURE AND FUNCTION
Authors: Loiselle A.E.
Published: January 2024

During aging, tendons demonstrate substantial disruptions in homeostasis, leading to impairments in structure-function. Impaired tendon function contributes to substantial declines quality of life during aging. Aged tendons are more likely to undergo spontaneous rupture, and the healing response following injury is impaired in aged tendons. Thus, there is a need to develop strategies to maintain tendon homeostasis and healing capacity through the lifespan. Tendon cell density sharply declines by ∼12 months of age in mice, and this low cell density is retained in geriatric tendons. Our data suggests that this decline in cellularity initiates a degenerative cascade due to insufficient production of the extracellular matrix (ECM) components needed to maintain tendon homeostasis. Thus, preventing this decline in tendon cellularity has great potential for maintaining tendon health. Single cell RNA sequencing analysis identifies two changes in the aged tendon cell environment. First, aged tendons primarily lose tenocytes that are associated with ECM biosynthesis functions. Second, the tenocytes that remain in aged tendons have disruptions in proteostasis and an increased pro-inflammatory phenotype, with these changes collectively termed ‘programmatic skewing'. To determine which of these changes drives homeostatic disruption, we developed a model of tenocyte depletion in young animals. This model decreases tendon cellularity to that of an aged tendon, including decreased biosynthetic tenocyte function, while age-related programmatic skewing is absent. Loss of biosynthetic tenocyte function in young tendons was sufficient to induce homeostatic disruption comparable to natural aging, including deficits in ECM organization, composition, and material quality, suggesting loss biosynthetic tenocytes as an initiator of tendon degeneration. In contrast, our data suggest that programmatic skewing underpins impaired healing in aged tendons. Indeed, despite similar declines in the tenocyte environment, middle-aged and young-depleted tendons mount a physiological healing response characterized by robust ECM synthesis and remodeling, while aged tendons heal with insufficient ECM.
TRP-CHANNELS IN TENDONS: FIRST INSIGHTS, NOVEL QUESTIONS
Authors: Lehner C. , Benedetti B. , Tempfer H. , Traweger A.
Published: January 2024

Tendinopathy is a disease associated with pain and tendon degeneration, leading to a decreased range of motion and an increased risk of tendon rupture. The etiology of this frequent disease is still unknown. In other musculoskeletal tissues like cartilage and intervertebral discs, transient receptor potential channels (TRP- channels) were shown to play a major role in the progression of degeneration. Due to their responsiveness to a wide range of stimuli like temperature, pH, osmolarity and mechanical load, they are potentially relevant factors in tendon degeneration as well. We therefore hypothesize that TRP- channels are expressed in tendon cells and respond to degeneration inducing stimuli.

By immunohistochemistry, qRT-PCR and western blot analyses, we found three TRP channel members, belonging to the vanilloid (TRPV), and ankyrin (TRPA) subfamily, respectively, to be expressed in healthy human tendon tissue as well as in rodent tendon, with expression being located to cells within the dense tendon proper, as well as to endotenon resident cells. In vitro-inflammatory and ex vivo-mechanical stimulation led to a significant upregulation of TRPA1 expression in tendon cells, which correlates well with the fact that TRPA1 is considered as mechanosensitive channel being sensitized by inflammatory mediators.

This is the first description of TRP- channels in human and rodent tendon. As these channels are pharmacologically targetable by both agonists and antagonists, they may represent a promising target for novel treatments of tendinopathy.
ESTABLISHING NOVEL MARKERS OF TENDON CELL POPULATIONS
Authors: Zamboulis D.E. , Ali F.S.S. , Thorpe C.T.
Published: January 2024

Energy storing tendons such as the human Achilles and equine superficial digital flexor tendon (SDFT) are prone to age-related injury. Tendons have poor healing capacity and a lack of effective treatments can lead to ongoing pain, reduced function and re-injury. It is therefore important to identify the mechanisms underpinning age-related tendinous changes in order to develop more effective treatments. Our recent single cell sequencing data has shown that tendon cell populations have extensive heterogeneity and cells housed in the tendon interfascicular matrix (IFM) are preferentially affected by ageing. There is, however, a lack of established surface markers for cell populations in tendon, limiting the capacity to isolate distinct cell populations and study their contribution to age-related tendon degeneration. Here, we investigate the presence of the cell surface proteins MET proto-oncogene (MET), integrin subunit alpha 10 (ITGA10), fibroblast activation protein alpha (FAP) and platelet derived growth factor receptor alpha (PDGFRA) in the equine SDFT cell populations and their co-localisation with known markers.

Using Western blot we validated the specificity of selected antibodies in equine tissue before performing immunohistochemistry to establish the location of the respective proteins in the SDFT. We subsequently used double labelling immunofluorescence with the established mural cell marker desmin (DES) to distinguish between tenocyte and mural cell populations.

In situ, MET, ITGA10, and FAP presence was found in cells throughout the tendon whereas PDGFRA was present in cells within the IFM. Double labelling immunofluorescence with the mural cell marker DES showed lack of co-localisation between PDGFRA and DES suggesting PDGFRA is labelling an IFM cell population distinct from those associated with blood vessels.

PDGFRA is a promising target for the specific cell sorting of IFM-localised tenocytes, enabling their isolation and subsequent characterisation.

Acknowledgments: The authors acknowledge the Biotechnology and Biological Sciences Research Council (BB/W007282/1) for funding this work.
PRODUCTION OF CLINICAL-GRADE EXTRACELLULAR VESICLES (EVS) SECRETED BY INDUCED PLURIPOTENT STEM CELL-DERIVED MESENCHYMAL STEM CELLS AND MESENCHYMAL STEM CELLS FOR THE TREATMENT OF OSTEOARTHRITIS
Authors: Palamà M.E.F. , Gorgun C. , Shaw G. , Mauphy M. , Gentili C.
Published: January 2024

Mesenchymal stem cells (MSCs) have been studied for the treatment of Osteoarthritis (OA), a potential mechanism of MSC therapies has been attributed to paracrine activity, in which extracellular vesicles (EVs) may play a major role. It is suggested that MSCs from younger donor compete with adult MSC in their EV production capabilities. Therefore, MSCs generated from induced pluripotent mesenchymal stem cells (iMSC) appear to provide a promising source. In this study, MSCs and iMSC during long term-expansion using a serum free clinical grade condition, were characterized for surface expression pattern, proliferation and differentiation capacity, and senescence rate. Culture media were collected continuously during cell expansion, and EVs were isolated. Nanoparticle tracking analysis (NTA), transmission electron microscopy, western blots, and flow cytometry were used to identify EVs. We evaluated the biological effects of MSC and iMSC-derived EVs on human chondrocytes treated with IL-1α, to mimic the OA environment.

In both cell types, from early to late passages, the amount of EVs detected by NTA increased significantly, EVs collected during cells expansion, retained tetraspanins (CD9, CD63 and CD81) expression. The anti-inflammatory activity of MSC-EVs was evaluated in vitro using OA chondrocytes, the expression of IL-6, IL-8 and COX-2 was significantly reduced after the treatment with hMSC-derived EVs isolated at early passage. The miRNA content of EVs was also investigated, we identify miRNA that are involved in specific biological function.

At the same time, we defined the best culture conditions to maintain iMSC and define the best time window in which to isolate EVs with highest biological activity.

In conclusion, a clinical grade serum-free medium was found to be suitable for the isolation and expansion of MSCs and iMSC with increased EVs production for therapeutic applications.

Acknowledgments: This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 874671
PLATELET-DERIVED EXTRACELLULAR VESICLES PROMOTE STEM CELL TENOGENIC COMMITMENT IN A BIOENGINEERED TENDON 3D MODEL
Authors: Graça A.L. , Domingues R.M.A. , Docheva D. , Gomez-Florit M. , Gomes M.E.
Published: January 2024

Worldwide, tendon disorders are one of the main causes of disability that decrease the quality of life of individuals and represent a substantial economic burden on society. Currently, the main therapies used for tendon injuries are not able to restore tendon functionality, and due to tendons' hypovascular and hypocellular nature, they present a reduced healing capacity, which also limits the success of the available therapies. In order to discover new therapies, extracellular vesicles (EVs), key players in cell-cell communication, have been widely explored for tissue engineering and regenerative medicine applications. Thus, the aim of this study is to assess the role of EVs derived from platelets in stem cell tenogenic commitment using a bioengineered tendon in vitro model for potential use as tendon therapeutic agents. Biomimetic platelet-derived EVs were produced by freeze-thaw cycles of platelets and isolation at different centrifugation speed. To recreate the architecture of tendons, a 3D system consisting of electrospun anisotropic nanofiber scaffolds coated with collagen encapsulating human adipose stem cells (hASCs) and different types of platelet-derived EVs, were produced. Then, the influence of the tendon-mimetic constructs and the distinct EVs populations in the hASCs tenogenic differentiation were assessed over culture time. We observed that the hASCs on the nanofibrous tendon scaffolds, show high cytoskeleton anisotropic organization that is characteristic of tenocytes. Moreover, acting as biological cues, platelet-derived EVs boosted hASCs tenogenic commitment, supported by the increased gene expression of tendon-related markers (SCX and TNMD). Additionally, EVs enhanced the deposition of tendon like extracellular matrix (ECM), as evidenced by the increased gene expression of ECM-related markers such as COL1, COL3, DCN, TNC, and MMP-3, which are fundamental for ECM synthesis and degradation balance. Moreover, EVs induced lower collagen matrix contraction on hASCs, which has been related with lower myofibroblast differentiation. Overall, the results revealed that EVs are capable of modulating stem cells' behavior boosting their tenogenic commitment, through the increased expression of healthy tendon cell markers, potentiating ECM deposition and decreasing cell contractility. Therefore, platelet EVs are a promising biochemical tool, worthy to be further explored, as paracrine signaling that might potentiate tendon repair and regeneration.
STEM CELLS IN BONE REGENERATION; THE FUTURE IS NOW
Authors: Gjerde C.
Published: January 2024

The aim of the ongoing projects was to demonstrate the efficacy of autologous bone marrow derived stem cells (MSC) combined with biomaterial to induced new bone formation in a randomized multicenter controlled clinical trial.

Patients with a need for bone reconstruction of residual edentulous ridges in both the mandible and maxilla due to bone defects with a vertical loss of alveolar bone volume and/or knife edge ridges (≤ than 4,5 mm) unable to provide adequate primary stabilization for dental implants were included in the clinical study. Autologous bone marrow MSC were expanded, loaded on BCP and used to augment the alveolar ridges. After five months bone biopsies were harvested at the implant position site and implants were installed in the regenerated bone. The implants were loaded after 8–12 weeks. Safety, efficacy, quality of life and success/survival were assessed. Five clinical centers, 4 different countries participated. Bone grafts harvested from the ramus of the mandibles were used as control in the projects.
APPLICATIONS OF ARTIFICIAL INTELLIGENCE IN THE EARLY DIAGNOSIS OF CHRONIC LOW BACK PAIN
Authors: Ambrosio L.
Published: January 2024

In the last decades, the use of artificial intelligence (AI) has been increasingly investigated in intervertebral disc degeneration (IDD) and chronic low back pain (LBP) research. To date, several AI-based cutting-edge technologies, such as computer vision, computer-assisted diagnosis, decision support system and natural language processing have been utilized to optimize LBP prevention, diagnosis, and treatment. This talk will provide an outline on contemporary AI applications to IDD and LBP research, with a particular attention towards actual knowledge gaps and promising innovative tools.
TRANSLATIONAL POTENTIAL OF MESENCHYMAL STEM CELL THERAPY FOR INTERVERTEBRAL DISC REGENERATION
Authors: Vadalá G.
Published: January 2024

The use of mesenchymal stem cell (MSCs) for intervertebral disc (IVD) regeneration has been extensively explored in the last two decades. MSCs are potent cell types that can be easily and safely harvested due to their abundancy and availability. Moreover, they are characterized by the capacity to differentiate towards IVD cells as well as release growth factors to support resident cell metabolism and recruit local progenitor cells to induce endogenous repair of degenerated IVDs. This talk will outline the characteristics of the main MSC sources and their effect towards IVD regeneration based on available preclinical and clinical evidence. In addition, innovative aspects of MSC-derived cell-free therapies will also be discussed.