Cellulose phosphates as biomaterials. In vivo biocompatibility studies.

Femoral implantation of regenerated cellulose hydrogels revealed their biocompatibility, but a complete osseointegration could not be observed. Phosphorylation was therefore envisaged as the means to enhance cellulose bioactivity. In vitro studies showed that regenerated cellulose hydrogels promote bone cells attachment and proliferation but do not mineralize in acellular simulated physiological conditions. On the contrary, phosphorylated cellulose has shown an opposite behavior, by inducing the formation of a calcium phosphate layer in simulated physiological conditions, but behaving as a poor substrate for bone cells attachment and proliferation. In order to investigate the in vivo behavior of these materials, and assess the influence of mineralization induction ability vs. bone cells compatibility, unmodified and phosphorylated cellulose hydrogels were implanted in rabbits for a maximum period of 6 months and bone regeneration was investigated. Despite the difficulties arising from the retraction of cellulose hydrogels upon dehydration during the preparation of retrieved implants, histological observations showed no inflammatory response after implantation, with bone intra-spongious regeneration of cells and the integration of the unmodified as well as the phosphorylated cellulose implants. After a maximum implantation period of 6 months, histological observations, histomorphometry and the measurement of the amount of 45Ca incorporated in the surrounding tissue indicated a slightly better osseointegration of phosphorylated cellulose, although no significant differences between the two materials were found.     

Concentrations of organochlorine pesticides in milk of Nicaraguan mothers

Breast-milk samples from 101 mothers from the basin of Rio Aloya, Nicaragua, were collected on two occasions within the first trimester of lactation. Milk samples were analyzed for 13 organochlorine pesticides: (1) p,p'-dichlorophenyldichloroethylene; (2) p,p'-dichlorophenyltrichloroethane; (3) p,p'-dichlorophenyldichlorodiene; (4) alpha-hexachlorocyclohexane; (5) beta-hexachlorocyclohexane; (6) gamma-hexachlorocyclohexane; (7) delta-hexachlorocyclohexane; (8) toxaphene; (9) dieldrin; (10) endrin; (11) aldrin; (12) heptachlor; and (13) heptachlor-epoxide. Organochlorines of the dichlorodiphenylethane class (i.e., p,p'-dichlorodiphenylethane and p,p'-dichlorodiphenylethane) were found in all samples and at the highest mean concentrations observed in the study. Chemicals in the hexachlorocyclohexane family (i.e., alpha- and delta-hexachlocyclohexane) were not found at all (0%), and the other hexachlorocyclohexane compounds (i.e., beta > gamma) were found in less than 6% of the samples. Twenty percent or less of the sample contained chlorInated cyclodienes (i.e., dieldrin > endrin > heptachlor-epoxide > heptachlor). No measurable concentrations of alpha-hexachlorocyclohexane, aldrin, p,p'-dichlorophenyldichlorodiene, and toxaphene were found in the breast milk samples. Analysis of variance demonstrated that only the concentration of p,p'-dichlorophenyldichloroethylene p,p'-dichlorophenyltrichloroethane, and endrin were affected significantly by maternal age. Overall, with the exception of p,p'-chlorophenyldichloroethylene, and p,p'-dichlorophenyltrichloroethane, the mean concentrations of the analyzed pesticides were low. Total p,p'-dichlorophenyltrichloroethane concentrations that exceeded the allowed daily intake set by the World Health Organisation were found in 5.9% of the samples.     

Fetal bovine serum‐free culture of endothelial progenitor cells—progress and challenges

Two decades after the first report on endothelial progenitor cells (EPC), their key role in postnatal vasculogenesis and vascular repair is well established. The therapeutic potential of EPC and their growing use in clinical trials calls for the development of more robust, reproducible, and safer methods for the in vitro expansion and maintenance of these cells. Despite many limitations associated with its usage, fetal bovine serum (FBS) is still widely applied as a cell culture supplement. Although different approaches aiming at establishing FBS‐free culture have been developed for many cell types, adequate solutions for endothelial cells, and for EPC in particular, are still scarce, possibly due to the multiple challenges that have to be faced when culturing these cells. In this review, we provide a brief overview on the therapeutic relevance of EPC and critically analyse the available literature on FBS‐free endothelial cell culture methods, including xeno‐free, serum‐free, and chemically defined systems.     

Fibroblasts as maestros orchestrating tissue regeneration

Fibroblasts constitute a dynamic and versatile population of cells of mesenchymal origin, implicated in both regenerative strategies and pathological conditions. Despite being frequently associated to disease development, particularly through the establishment of fibrotic tissue, fibroblasts hold great potential for tissue engineering and regenerative medicine applications. They are responsible for synthesizing and depositing extracellular matrix components, allowing other cells to settle and migrate along a three‐dimensional support and thereby generating an organ‐specific architecture. Additionally, they produce bioactive molecules that are involved in several physiological processes, including angiogenesis and tissue repair. Although there seems to be much still to unveil about these fascinating cells they have been attracting increasing interest and are now being intensively explored as a cell source to develop bioengineered tissue constructs or to improve stem cell‐based technologies. This review intends to highlight the potential of fibroblasts in orchestrating tissue regeneration, as well as to contribute to uncover uncharted prospective applications of these cells. Copyright © 2017 John Wiley & Sons, Ltd.     

The plexin C1 receptor promotes acute inflammation

Acute inflammation is the pathophysiological basis of important clinical conditions associated with organ failure. The initial inflammatory response is controlled by the chemokine system, yet recent data have indicated that the neuronal guidance cues are significantly involved in the orchestration of this process. Previous work has shown the proinflammatory capacity of the guidance cue semaphorin (Sema) 7a, but the role of one of its target receptors, the plexin C1 (PLXNC1) receptor is to date unknown. We report here that PLXNC1 is expressed outside the nervous system and induced during acute inflammation. PLXNC1^?/? mice with C57BL/6 background demonstrated decreased inflammatory responses during zymosan A (ZyA)‐induced peritonitis. Subsequent in vivo studies revealed altered rolling, adhesion, and transmigration properties of PLXNC1^?/? leukocytes. Blockade of PLXNC1 was associated with attenuated chemotactic transendothelial migration properties in vitro. Studies in chimeric mice revealed that hematopoietic PLXNC1^?/? animals demonstrated an attenuated inflammatory response. To probe the therapeutic potential of PLXNC1 we treated C57BL/6 WT mice with an anti‐PLXNC1 antibody and a PLXNC1 binding peptide. Both of these interventions significantly dampened ZyA‐induced peritonitis. These results implicate an important role of PLXNC1 during an acute inflammatory response and indicate PLXNC1 as a potential target for the control of conditions associated with acute inflammation.     

Multifunctional magnetic-responsive hydrogels to engineer tendon-to-bone interface

Photocrosslinkable magnetic hydrogels are attracting great interest for tissue engineering strategies due to their versatility and multifunctionality, including their remote controllability ex vivo, thus enabling engineering complex tissue interfaces. This study reports the development of a photocrosslinkable magnetic responsive hydrogel made of methacrylated chondroitin sulfate (MA-CS) enriched with platelet lysate (PL) with tunable features, envisioning their application in tendon-to-bone interface. MA-CS coated iron-based magnetic nanoparticles were incorporated to provide magnetic responsiveness to the hydrogel. Osteogenically differentiated adipose-derived stem cells and/or tendon-derived cells were encapsulated within the hydrogel, proliferating and expressing bone- and tendon-related markers. External magnetic field (EMF) application modulated the swelling, degradation and release of PL-derived growth factors, and impacted both cell morphology and the expression and synthesis of tendon- and bone-like matrix with a more evident effect in co-cultures. Overall, the developed magnetic responsive hydrogel represents a potential cell carrier system for interfacial tissue engineering with EMF-controlled properties.