Soft interfacial materials, such as self-assembled polymer membranes, are gaining increasing interest as biomaterials since they can provide selective barriers and/or controlled affinity interactions important to regulate cellular processes. Herein, we report the design and fabrication of multiscale structured membranes integrating selective molecular functionalities for potential applications in bone regeneration. The membranes were obtained by interfacial self-assembly of miscible aqueous solutions of hyaluronan and multi-domain peptides (MDPs) incorporating distinct biochemical motifs, including mineralizing (EE), integrin-binding (RGDS) and osteogenic (YGFGG) peptide sequences. Circular dichroism and Fourier transform infrared spectroscopy analyses of the MDPs revealed a predominant β-sheet conformation, while transmission electron microscopy (TEM) showed the formation of fibre-like nanostructures with different lengths. Scanning electron microscopy (SEM) of the membranes showed an anisotropic structure and surfaces with different nanotopographies, reflecting the morphological differences observed under TEM. All the membranes were able to promote the deposition of a calcium-phosphate mineral on their surface when incubated in a mineralizing solution. The ability of the MDPs, coated on coverslips or presented within the membranes, to support cell adhesion was investigated using primary adult periosteum-derived cells (PDCs) under serum-free conditions. Cells on the membranes lacking RGDS remained round, while in the presence of RGDS they appear to be more elongated and anchored to the membrane. These observations were confirmed by SEM analysis that showed cells attached to the membrane and exhibiting an extended morphology with close interactions with the membrane surface. We anticipate that these molecularly designed interfacial membranes can both provide relevant biochemical signals and structural biomimetic components for stem cell growth and differentiation and ultimately promote bone regeneration.
The metabolic capacity of many cells is tightly regulated and can adapt to changes in metabolic resources according to environmental changes. Tissue-resident memory (T
RM
) CD8
+
T cells are one of the most abundant T cell populations and offer rapid protection against invading pathogens, especially at the epithelia. T
RM
cells metabolically adapt to their tissue niche, such as the intestinal epithelial barrier. In the small intestine, the types of T
RM
cells are intraepithelial lymphocytes (IELs), which contain high levels of cytotoxic molecules and express activation markers, suggesting a heightened state of activation. We hypothesize that the tissue environment may determine IEL activity. We show that IEL activation, in line with its semiactive status, is metabolically faster than circulating CD8
+
T cells. IEL glycolysis and oxidative phosphorylation (OXPHOS) are interdependently regulated and are dependent on rapid access to metabolites from the environment. IELs are restrained by local availability of metabolites, but, especially, glucose levels determine their activity. Importantly, this enables functional control of intestinal T
RM
cells by metabolic means within the fragile environment of the intestinal epithelial barrier.
Over the last decade, studies have evaluated the effectiveness of interventions for juvenile offenders; nonetheless, those studies were more focused on recidivism than on the mechanisms associated with criminal perpetration. The current study explores the role of juvenile justice involvement and detention measures in a set of psychological, social, and criminal behavior characteristics in early adulthood. Seventy-five young adults with official records of juvenile delinquency in 2010-2011 and 240 young adults from the community filled out our protocol in 2014-2015. Young adults with juvenile justice involvement showed worse psychological, social, and criminal outcomes than those from community. Detention appears to be related to the number of deviant friends, delinquency, and school achievement in early adulthood. Our findings are in line with the labeling and deviant peer contagion theories and establish the main areas of interventions that affect the identified needs. A set of policy implications is provided.
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