While the studies on the material interaction with mesenchymal stem cells (MSCs) have been mainly focused on the ability of materials to provide environment to regulate cell viability, proliferation or differentiation, the therapeutic effects of MSC-material constructs may result from the secretion of immunomodulatory and angiogenic cytokines from MSCs. Here, electrospun scaffolds composed of fibers in random, aligned and mesh-like patterns were fabricated, and the paracrine behavior of adipose-derived MSCs (Ad-MSCs) on the scaffolds were investigated in comparison to the cell culture via conventional microplates. It was found that the Ad-MSCs on the electrospun fibers produced significantly higher levels of anti-inflammatory and pro-angiogenic cytokines compared to those cultured on microplates. The enhanced modulatory effects of the secreted products of Ad-MSCs on fibrous electrospun scaffolds were also proven in the cultures of endothelial cells and the LPS-stimulated macrophages, with three types of scaffolds showing distinct influences on the paracrine function of Ad-MSCs. In a skin excisional wound-healing model in rat, the conditioned medium collected from the MSC-scaffold system accelerated the wound closure, promoted the macrophage recruitment and enhanced the polarization of macrophages toward the pro-healing phenotype in the wound bed. Our study demonstrates that the fibrous topography of scaffolds is a key material property that modulates the paracrine function of cells. The discovery elucidates a new aspect of material functions, laying the foundation for developing scaffold materials to promote tissue regeneration/repair through guiding the paracrine signaling network.

Objective Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable, neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. Method The primary analyses utilized a cross-disorder design for 2,699 patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. Results Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p=.09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 patient deletions: 0 control deletions, p=0.08 in current study, p=0.025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support to the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in autism or schizophrenia (2–4%). Conclusion Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes.

We have quantified the release of polychlorinated biphenyls (PCBs) from Indiana Harbor and Ship Canal (IHSC) to Lake Michigan and the atmosphere. Navigational dredging is planned for this system and there is concern that dredging will result in releases of PCBs. We have measured >158 PCBs in surficial sediment, water, suspended particles, and air. We predicted the release of PCBs from sediments to water and from water to air. To quantify the level of confidence in our calculations, we used a Monte Carlo simulation for each congener flux. We determined that 4±0.05 kg of ΣPCBs were released from the sediment to the water and 7±0.1 kg of ΣPCBs were volatilized from the water to the air annually. We measured input from the upstream regions of the canal system of 45.0 kg yr−1 and export to Lake Michigan of 43.9 kg yr−1. The ΣPCBs mass balance accounts for nearly all the PCB inputs and losses to the navigational regions. The congener profiles in sediment, water, and air support our determination that the contaminated sediment is a major source of PCBs into the water and air above it. We have shown that the system is currently a significant source of PCBs to the air and to Lake Michigan, even under quiescent conditions.

The nerve conduit with biofunctionalities can regulate neurite outgrowth, as well as the migration, proliferation, and myelination activity of Schwann cells. In the present study, polycaprolactone (PCL) conduits are coated with Naphthalene-phenylalanine-phenylalanine-glycine-arginine-glycine-aspartic (Nap-FFGRGD) and Naphthalene-phenylalanine-phenylalanine-glycine-cysteine-aspartic-proline-glycine-tyrosine-isoleucine-glycine-serine-arginine (Nap-FFGCDPGYIGSR) by self-assembly. In vitro studies demonstrate that arginine-glycine-aspartic (RGD) and tyrosine-isoleucine-glycine-serine-arginine (YIGSR) are capable of synergistically enhancing the ability of PCL to support the adhesion and proliferation of Schwann cells, as well as increasing neurite outgrowth from dorsal root ganglions explants. This synergistic effect may occur via the activation of both the phosphoinositide 3-kinase/protein kinase B and mitogen-activated protein kinase/extracellular signal-regulated protein kinase pathways. RGD/YIGSR modifications demonstrate beneficial effects across a 15 mm sciatic nerve gap in axonal regeneration and functional recovery. In addition, increased vascularization is observed in the RGD/YIGSR-PCL group, which might contribute to their beneficial effects on nerve regeneration. These findings indicate the potential of the RGD/YIGSR-PCL conduit to promote axonal regeneration and functional recovery, making the RGD/YIGSR-PCL conduit an attractive candidate for the treatment of a critical nerve defect.