In bone engineering, the adhesion, proliferation and differentiation of mesenchymal stromal cells rely on signaling from chemico-physical structure of the substrate, therefore prompting the design of mimetic “extracellular matrix”-like scaffolds. In this study, three-dimensional porous poly-L-lactic acid (PLLA)-based scaffolds have been mixed with different components, including single walled carbon nanotubes (CNT), micro-hydroxyapatite particles (HA), and BMP2, and treated with plasma (PT), to obtain four different nanocomposites: PLLA + CNT, PLLA + CNTHA, PLLA + CNT + HA + BMP2 and PLLA + CNT + HA + PT. Adult bone marrow mesenchymal stromal cells (MSCs) were derived from the femur of orthopaedic patients, seeded on the scaffolds and cultured under osteogenic induction up to differentiation and mineralization. The release of specific metabolites and temporal gene expression profiles of marrow-derived osteoprogenitors were analyzed at definite time points, relevant to in vitro culture as well as in vivo differentiation. As a result, the role of the different biomimetic components added to the PLLA matrix was deciphered, with BMP2-added scaffolds showing the highest biomimetic activity on cells differentiating to mature osteoblasts. The modification of a polymeric scaffold with reinforcing components which also work as biomimetic cues for cells can effectively direct osteoprogenitor cells differentiation, so as to shorten the time required for mineralization.

Chronic inflammatory autoimmune disorders are systemic diseases with increasing incidence and still lack a cure. More recently, attention has been placed in understanding gastrointestinal (GI) dysbiosis and, although important progress has been made in this area, it is currently unclear to what extent microbiome manipulation can be used in the treatment of autoimmune disorders. Via the use of appropriate models, rheumatoid arthritis (RA), a well-known exemplar of such pathologies, can be exploited to shed light on the currently overlooked effects of existing therapies on the GI microbiome. In this direction, we here explore the crosstalk between the GI microbiome and the host immunity in model arthritis (collagen induced arthritis, CIA). By exploiting omics from samples of limited invasiveness (blood and stools), we assess the host-microbiome responses to standard therapy (methotrexate, MTX) combined with mechanical subcutaneous stimulation (MS) and to mechanical stimulation alone. When MS is involved, results reveal the sphingolipid metabolism as the trait d’union among known hallmarks of (model) RA, namely: Imbalance in the S1P-S1PR1 axis, expansion of Prevotella sp., and invariant Natural Killer T (iNKT)-penia, thus offering the base of a rationale to mechanically modulate this pathway as a therapeutic target in RA.

The paper first focuses on morphological history of a landscape unit, consisting of biological deserts and wrecks of the endangered landscape. Secondly, it analyzes and elaborates hydrological scenarios to explore and discuss potential design strategies. Water margin continuity could be recovered through development of flooding strategies. In conclusion, form of the archipelago emerges as a specificity of the landscape unit. More than a metaphor but as a conceptual and programmatic dispositive, archipelago can inform on dynamic structure of the Bassa Friulana complex system within an ecological framework.