Functionalising Collagen-Based Scaffolds With Platelet-Rich Plasma for Enhanced Skin Wound Healing Potential.

Porous collagen-glycosaminoglycan (collagen-GAG) scaffolds have shown promising clinical results for wound healing; however, these scaffolds do not replace the dermal and epidermal layer simultaneously and rely on local endogenous signaling to direct healing. Functionalizing collagen-GAG scaffolds with signaling factors, and/or additional matrix molecules, could help overcome these challenges. An ideal candidate for this is platelet-rich plasma (PRP) as it is a natural reservoir of growth factors, can be activated to form a fibrin gel, and is available intraoperatively. We tested the factors released from PRP (PRPr) and found that at specific concentrations, PRPr enhanced cell proliferation and migration and induced angiogenesis to a greater extent than fetal bovine serum (FBS) controls. This motivated us to develop a strategy to successfully incorporate PRP homogeneously within the pores of the collagen-GAG scaffolds. The composite scaffold released key growth factors for wound healing (FGF, TGFß) and vascularization (VEGF, PDGF) for up to 14 days. In addition, the composite scaffold had enhanced mechanical properties (when compared to PRP gel alone), while providing a continuous upper surface of extracellular matrix (ECM) for keratinocyte seeding. The levels of the factors released from the composite scaffold were sufficient to sustain proliferation of key cells involved in wound healing, including human endothelial cells, mesenchymal stromal cells, fibroblasts, and keratinocytes; even in the absence of FBS supplementation. In functional in vitro and in vivo vascularization assays, our composite scaffold demonstrated increased angiogenic and vascularization potential, which is known to lead to enhanced wound healing. Upon pro-inflammatory induction, macrophages released lower levels of the pro-inflammatory marker MIP-1α when treated with PRPr; and released higher levels of the anti-inflammatory marker IL1-ra upon both pro- and anti-inflammatory induction when treated with the composite scaffold. Finally, our composite scaffold supported a co-culture system of human fibroblasts and keratinocytes that resulted in an epidermal-like layer, with keratinocytes constrained to the surface of the scaffold; by contrast, keratinocytes were observed infiltrating the PRP-free scaffold. This novel composite scaffold has the potential for rapid translation to the clinic by isolating PRP from a patient intraoperatively and combining it with regulatory approved scaffolds to enhance wound repair.

Volar locking plate fixation of distal radius fractures: use of an intra-operative 'carpal shoot through' view to identify dorsal compartment and distal radioulnar joint screw penetration.

INTRODUCTION: We report our experience using a 'carpal shoot through' view of the distal radius to identify dorsal compartment screw penetration intra-operatively when performing volar plating of the distal radius. METHODS: A prospective study of 42 patients (mean age 56 years) with acute distal radius fractures treated with open reduction internal fixation was undertaken. Surgical fixation was performed using a volar locking plate in all patients. After plate application, inclined posteroanterior and lateral radiographs were taken followed by the carpal shoot through view. RESULTS: In six cases (14 %), the carpal shoot through view revealed dorsal screw protrusion, which was not detectable on standard PA and lateral views. In one case, a screw had penetrated the distal radioulnar joint (DRUJ), which was only apparent on the shoot through view. The overall screw exchange rate was 17 %. CONCLUSIONS: Using the hand and carpus to minimise the contrast in X-ray penetration, the dorsal cortex of the distal radius may be imaged intra-operatively and dorsal compartment screw penetration detected in cases with significant multifragmentation when screw measurement is difficult. This view potentially reduces the risk of post-operative pain and extensor tendon injury and also provides excellent visualisation of the DRUJ.

Chloride molecular doping technique on 2D materials: WS2 and MoS2.

Low-resistivity metal-semiconductor (M-S) contact is one of the urgent challenges in the research of 2D transition metal dichalcogenides (TMDs). Here, we report a chloride molecular doping technique which greatly reduces the contact resistance (Rc) in the few-layer WS2 and MoS2. After doping, the Rc of WS2 and MoS2 have been decreased to 0.7 kΩ·µm and 0.5 kΩ·µm, respectively. The significant reduction of the Rc is attributed to the achieved high electron-doping density, thus a significant reduction of Schottky barrier width. As a proof-of-concept, high-performance few-layer WS2 field-effect transistors (FETs) are demonstrated, exhibiting a high drain current of 380 µA/µm, an on/off ratio of 4 × 10(6), and a peak field-effect mobility of 60 cm(2)/(V·s). This doping technique provides a highly viable route to diminish the Rc in TMDs, paving the way for high-performance 2D nanoelectronic devices.

Origin of p(2 x 1) phase on Si(001) by noncontact atomic force microscopy at 5 k.

The controversial issue of the origin of the p(2 x 1) reconstruction of the Si(001) surface observed in recent low temperature scanning tunneling microscopy experiments is clarified here using 5 K noncontact atomic force microscopy. The c(4 x 2) phase is observed at separations corresponding to weak tip-surface interactions, confirming that it is the ground state of the surface. At larger frequency shifts the p(2 x 1) phase of symmetric dimers is observed. By studying the interaction of a reactive Si tip with the c(4 x 2) Si(001) surface using an ab initio method, we find that the observed change in the surface reconstruction is an apparent effect caused by tip induced dimer flipping resulting in a modification of the surface structure and appearance of the p(2 x 1) phase in the image. Using an appropriate scanning protocol, one can manipulate the surface reconstruction at will, which has significance in nanotechnology.

The novel nucleoside analog R1479 (4'-azidocytidine) is a potent inhibitor of NS5B-dependent RNA synthesis and hepatitis C virus replication in cell culture.

Hepatitis C virus (HCV) polymerase activity is essential for HCV replication. Targeted screening of nucleoside analogs identified R1479 (4'-azidocytidine) as a specific inhibitor of HCV replication in the HCV subgenomic replicon system (IC(50) = 1.28 microM) with similar potency compared with 2'-C-methylcytidine (IC(50) = 1.13 microM). R1479 showed no effect on cell viability or proliferation of HCV replicon or Huh-7 cells at concentrations up to 2 mM. HCV replicon RNA could be fully cleared from replicon cells after prolonged incubation with R1479. The corresponding 5'-triphosphate derivative (R1479-TP) is a potent inhibitor of native HCV replicase isolated from replicon cells and of recombinant HCV polymerase (NS5B)-mediated RNA synthesis activity. R1479-TP inhibited RNA synthesis as a CTP-competitive inhibitor with a K(i) of 40 nM. On an HCV RNA-derived template substrate (complementary internal ribosome entry site), R1479-TP showed similar potency of NS5B inhibition compared with 3'-dCTP. R1479-TP was incorporated into nascent RNA by HCV polymerase and reduced further elongation with similar efficiency compared with 3'-dCTP under the reaction conditions. The S282T point mutation in the coding sequence of NS5B confers resistance to inhibition by 2'-C-MeATP and other 2'-methyl-nucleotides. In contrast, the S282T mutation did not confer cross-resistance to R1479.