Marίa Zambrano interpreta Spinoza e Hegel

María Zambrano begins her study of Spinoza with her doctoral thesis La salvacíon del individuo en Spinoza. The Dutch philosopher is, for her, a milestone in the evolution of philosophy, especially for Spinoza’s concept of Totality, of Deus causa sui and Deus sive natura. The philosophical speculation of the Spanish philosopher ends, however, with Hegel, whose idea of history as a necessary and relentless experience of the Geist, she interpretes in an original way.María Zambrano empieza su estudio de Spinoza con su tesi doctoral La salvacíon del individuo en Spinoza. El filósofo neerlandés es, para ella, una persona clave y fundamental  dentro de la evolución de la filosofía, sobre todo por el concepto que Spinoza tiene de la Totalidad, de Dios como causa sui y Deus sive natura. La especulación filosófica de la filósofa andaluza finaliza, sin embargo, con Hegel, de quien interpreta, de una manera original, la idea de la Historia como  experiencia implacable y necesaria del Geist.   &nbsp

First steps to define murine amniotic fluid stem cell microenvironment

Stem cell niche refers to the microenvironment where stem cells reside in living organisms. Several elements define the niche and regulate stem cell characteristics, such as stromal support cells, gap junctions, soluble factors, extracellular matrix proteins, blood vessels and neural inputs. In the last years, different studies demonstrated the presence of cKit+ cells in human and murine amniotic fluid, which have been defined as amniotic fluid stem (AFS) cells. Firstly, we characterized the murine cKit+ cells present both in the amniotic fluid and in the amnion. Secondly, to analyze the AFS cell microenvironment, we injected murine YFP+ embryonic stem cells (ESC) into the amniotic fluid of E13.5 wild type embryos. Four days after transplantation we found that YFP+ sorted cells maintained the expression of pluripotency markers and that ESC adherent to the amnion were more similar to original ESC in respect to those isolated from the amniotic fluid. Moreover, cytokines evaluation and oxygen concentration analysis revealed in this microenvironment the presence of factors that are considered key regulators in stem cell niches. This is the first indication that AFS cells reside in a microenvironment that possess specific characteristics able to maintain stemness of resident and exogenous stem cells

Allogenic tissue-specific decellularized scaffolds promote long-term muscle innervation and functional recovery in a surgical diaphragmatic hernia model

Congenital diaphragmatic hernia (CDH) is a neonatal defect in which the diaphragm muscle does not develop properly, thereby raising abdominal organs into the thoracic cavity and impeding lung development and function. Large diaphragmatic defects require correction with prosthetic patches to close the malformation. This treatment leads to a consequent generation of unwelcomed mechanical stress in the repaired diaphragm and hernia recurrences, thereby resulting in high morbidity and significant mortality rates. We proposed a specific diaphragm-derived extracellular matrix (ECM) as a scaffold for the treatment of CDH. To address this strategy, we developed a new surgical CDH mouse model to test the ability of our tissue-specific patch to regenerate damaged diaphragms. Implantation of decellularized diaphragmatic ECM-derived patches demonstrated absence of rejection or hernia recurrence, in contrast to the performance of a commercially available synthetic material. Diaphragm-derived ECM was able to promote the generation of new blood vessels, boost long-term muscle regeneration, and recover host diaphragmatic function. In addition, using a GFP\u202f+\u202fSchwann cell mouse model, we identified re-innervation of implanted patches. These results demonstrated for the first time that implantation of a tissue-specific biologic scaffold is able to promote a regenerating diaphragm muscle and overcome issues commonly related to the standard use of prosthetic materials

High contrast microstructural visualization of natural acellular matrices by means of phase-based x-ray tomography

Acellular scaffolds obtained via decellularization are a key instrument in regenerative medicine both per se and to drive the development of future-generation synthetic scaffolds that could become available off-the-shelf. In this framework, imaging is key to the understanding of the scaffolds\u2019 internal structure as well as their interaction with cells and other organs, including ideally post-implantation. Scaffolds of a wide range of intricate organs (esophagus, lung, liver and small intestine) were imaged with x-ray phase contrast computed tomography (PC-CT). Image quality was sufficiently high to visualize scaffold microarchitecture and to detect major anatomical features, such as the esophageal mucosal-submucosal separation, pulmonary alveoli and intestinal villi. These results are a long-sought step for the field of regenerative medicine; until now, histology and scanning electron microscopy have been the gold standard to study the scaffold structure. However, they are both destructive: hence, they are not suitable for imaging scaffolds prior to transplantation, and have no prospect for post-transplantation use. PC-CT, on the other hand, is non-destructive, 3D and fully quantitative. Importantly, not only do we demonstrate achievement of high image quality at two different synchrotron facilities, but also with commercial x-ray equipment, which makes the method available to any research laboratory

Customized bioreactor enables the production of 3D diaphragmatic constructs influencing matrix remodeling and fibroblast overgrowth

The production of skeletal muscle constructs useful for replacing large defects in vivo, such as in congenital diaphragmatic hernia (CDH), is still considered a challenge. The standard application of prosthetic material presents major limitations, such as hernia recurrences in a remarkable number of CDH patients. With this work, we developed a tissue engineering approach based on decellularized diaphragmatic muscle and human cells for the in vitro generation of diaphragmatic-like tissues as a proof-of-concept of a new option for the surgical treatment of large diaphragm defects. A customized bioreactor for diaphragmatic muscle was designed to control mechanical stimulation and promote radial stretching during the construct engineering. In vitro tests demonstrated that both ECM remodeling and fibroblast overgrowth were positively influenced by the bioreactor culture. Mechanically stimulated constructs also increased tissue maturation, with the formation of new oriented and aligned muscle fibers. Moreover, after in vivo orthotopic implantation in a surgical CDH mouse model, mechanically stimulated muscles maintained the presence of human cells within myofibers and hernia recurrence did not occur, suggesting the value of this approach for treating diaphragm defects

Lessons learned from pre-clinical testing of xenogeneic decellularized esophagi in a rabbit model

Summary Decellularization of esophagi from several species for tissue engineering is well described, but successful implantation in animal models of esophageal replacement has been challenging. The purpose of this study was to assess feasibility and applicability of esophageal replacement using decellularized porcine esophageal scaffolds in a new pre-clinical model. Following surgical replacement in rabbits with a vascularizing muscle flap, we observed successful anastomoses of decellularized scaffolds, cues of early neovascularization, and prevention of luminal collapse by the use of biodegradable stents. However, despite the success of the surgical procedure, the long-term survival was limited by the fragility of the animal model. Our results indicate that transplantation of a decellularized porcine scaffold is possible and vascular flaps may be useful to provide a vascular supply, but long-term outcomes require further pre-clinical testing in a different large animal model

Hydrogel-in-hydrogel live bioprinting for guidance and control of organoids and organotypic cultures

Three-dimensional hydrogel-based organ-like cultures can be applied to study development, regeneration, and disease in vitro. However, the control of engineered hydrogel composition, mechanical properties and geometrical constraints tends to be restricted to the initial time of fabrication. Modulation of hydrogel characteristics over time and according to culture evolution is often not possible. Here, we overcome these limitations by developing a hydrogel-in-hydrogel live bioprinting approach that enables the dynamic fabrication of instructive hydrogel elements within pre-existing hydrogel-based organ-like cultures. This can be achieved by crosslinking photosensitive hydrogels via two-photon absorption at any time during culture. We show that instructive hydrogels guide neural axon directionality in growing organotypic spinal cords, and that hydrogel geometry and mechanical properties control differential cell migration in developing cancer organoids. Finally, we show that hydrogel constraints promote cell polarity in liver organoids, guide small intestinal organoid morphogenesis and control lung tip bifurcation according to the hydrogel composition and shape

MAR\ucdA ZAMBRANO. L\u2019AVVENTURA DI ESSERE FILOSOFA: PENSIERO E AZIONE.

Il vivo interesse che, in particolare nell\u2019ultimo trentennio, si \ue8 registrato in Italia per il pensiero filosofico di Mar\ueda Zambrano \ue8 il motivo principale di questo lavoro. All\u2019interno della considerevole letteratura gi\ue0 esistente, si propone un\u2019analisi critica del pensiero zambraniano a partire dai suoi primi scritti. Nel pensiero spagnolo del XX secolo Zambrano segna una delle traiettorie pi\uf9 originali e, forse, \ue8 tra le filosofe europee che ancora continuano a suscitare intenso interesse, a giudicare dalle numerose tesi, ricerche e traduzioni delle sue opere. Cruciale \ue8 la critica che lei muove alla tradizione filosofica occidentale e alla ragione discorsiva e sistematica dei filosofi. Paradigmatico \ue8, fra l\u2019altro, il suo invito a praticare un pensiero che sveli le fallacie della tradizione filosofica. A suo avviso, si tratta di ridefinire lo statuto filosofico perch\ue9 accolga un altro modello di ragione. Un esempio \ue8 quello che lei propone con la ragione poetica. Essa non \ue8 solo ragione, e non \ue8 solo poesia, in quanto \ue8 insieme ragione e poesia. Questa ricerca \ue8 suddivisa in due parti. Nella prima, l\u2019attenzione \ue8 focalizzata, in particolare, sul decennio cruciale per la storia spagnola, che va dal 1928 al 1939. Il che porta, a orientarci pi\uf9 nel dettaglio, sui prodromi del pensiero poetico e filosofico di Mar\ueda Zambrano, a partire dai suoi studi, in Madrid, con Jos\ue9 Ortega y Gasset e Manuel Garc\ueda Morente, Xavier Zubiri e J. Besteiro; dai suoi contatti con i pi\uf9 noti poeti spagnoli, come Antonio Machado, Emilio Prados, Miguel Hernand\ue9z; dalle sue relazioni politico-culturali come, per esempio, l\u2019associazionismo universitario. La seconda parte di questa ricerca intende mostrare, invece, attraverso alcune testimonianze paradigmatiche, quelle orme visibili e indelebili di una generazione in crisi, per l\u2019appunto, della Generaci\uf3n del Toro. Questa ricerca ha anche due esigenze metodologiche. A partire dal lavoro di dottorato su Spinoza, mai concluso e che, per\uf2, lei riepilog\uf2 in un manoscritto e in un pregnante articolo, si segnalano alcuni dei nodi teoretici pi\uf9 rilevanti della lettura dell\u2019autrice. In tal senso, \ue8 utile rileggere, anche, il rapporto complesso con Ortega, studioso attento della filosofia spinoziana e della politica spagnola, attraverso, fra l\u2019altro, alcune delle lettere che Zambrano gli invia negli anni Trenta. \uc8 interessante inoltre ricordare il suo impegno civile e politico, avviato gi\ue0 prima dell\u2019avvento della dittatura \uabprimoriverista\ubb e che segna, di fatto, una tappa importante della sua critica filosofica. Il che \ue8 cruciale anche per ricostruire, storicamente, i movimenti giovanili e le associazioni studentesche che proprio in questo contesto contribuirono ad accelerare quel processo di rimodernizzazione politico-culturale della penisola iberica.The lively interest , recorded in Italy, particularly in the last three decades, for the philosophical thought of Mar\ueda Zambrano is the main reason of this work. Within the considerable existing literature , we propose a critical analysis of zambranian thought starting from his early writings. In the Spanish thought of the twentieth century Zambrano marks one of the most original trajectories and, perhaps, is one of the European philosophers who still continue to arouse intense interest , judging by the many theses, research and translations of his works. Crucial is the criticism that she moves to the Western philosophical tradition and to discursive and systematic reason of philosophers. Paradigmatic is , among other things , his invitation to practice a thought that reveal the fallacies of the philosophical tradition . In her view, it has to be redefined the philosophical status in order to accept another model of reason . An example is what she proposes with the poetic reason . It is not just reason, and not just poetry , as it is both reason and poetry. This research is divided into two parts. In the first, the attention is focused in particular on the crucial decade for Spanish history , which goes from 1928 to 1939 . This leads , to orient ourselves in more detail, about the beginnings of the poetic and philosophical thought of Mar\ueda Zambrano , from his studies in Madrid with Jos\ue9 Ortega y Gasset and Manuel Garc\ueda Morente , Xavier Zubiri and J. Besteiro , from his contacts with the most important Spanish poets such as Antonio Machado, Emilio Prados, Miguel Hernand\ue9z , its political and cultural relations as , for example, university associations . The second part of this research will show , however, through some paradigmatic testimonials those visible and indelible footsteps of a generation in crisis , in fact , of the Generaci\uf3n of Toro . This research also has two methodological requirements . Since doctoral work on Spinoza , never-ended and that, though, she summarized in a manuscript and in a meaningful article , we highlight some of the most relevant theoretical nodes of the reading of the author. In this sense , it is useful to recall , too, the complex relationship with Ortega, careful student of the philosophy of Spinoza and Spanish politics , through some of the letters that Zambrano sends in the Thirties. It is also interesting to recall his civil and political commitment , which began even before the advent of the " primoriverist " dictatorship and that marks , in fact, an important stage of her philosophical critique . Which is also crucial to reconstruct , historically , youth movements and student associations in this context that helped to accelerate the process of a political-cultural modernization of the Iberian Peninsula