Development of an Antimicrobial Peptide SAAP-148-Functionalized Supramolecular Coating on Titanium to Prevent Biomaterial-Associated Infections

Titanium implants are widely used in medicine but have a risk of biomaterial-associated infection (BAI), of which traditional antibiotic-based treatment is affected by resistance. Antimicrobial peptides (AMPs) are used to successfully kill antibiotic-resistant bacteria. Herein, a supramolecular coating for titanium implants is developed which presents the synthetic antimicrobial and antibiofilm peptide SAAP-148 via supramolecular interactions using ureido-pyrimidinone supramolecular units (UPy-SAAP-148GG). Material characterization of dropcast coatings shows the presence of UPy-SAAP-148GG at the surface. The supramolecular immobilized peptide remains antimicrobially active in dropcast polymer films and can successfully kill (antibiotic-resistant) Staphylococcus aureus, Acinetobacter baumannii, and Escherichia coli. Minor toxicity for human dermal fibroblasts is observed, with a reduced cell attachment after 24 h. Subsequently, a dipcoat coating on titanium implants is developed and tested in vivo in a subcutaneous implant infection mouse model with S. aureus administered locally on the implant before implantation to mimic contamination during surgery. The supramolecular coating containing 5 mol% of UPy-SAAP-148GG significantly prevents colonization of the implant surface as well as of the surrounding tissue, with no signs of toxicity. This shows that supramolecular AMP coatings on titanium are eminently suitable to prevent BAI.</p

Heparin-guided binding of vascular endothelial growth factor to supramolecular biomaterial surfaces

Growth factors can steer the biological response to a biomaterial post implantation. Heparin is a growth factor binding molecule that can coordinate growth factor presentation to cells and therefore is able to regulate many biological processes. One way to functionalize biomaterials with heparin and growth factors is via a supramolecular approach. Here, we show a proof-of-concept study in which a supramolecular approach based on ureido-pyrimidinone (UPy) was used, which allows for modular functionalization. PCLdiUPy was functionalized with a UPy-modified heparin binding peptide (UPy-HBP) to facilitates binding of heparin, which in turn can bind vascular endothelial growth factor (VEGF) via its heparin binding domain. The adsorption of both heparin and VEGF were studied in two different functionalization approaches (pre-complex and two-step) and at different molecular ratios. Quartz crystal microbalance with dissipation energy adsorption data showed that VEGF and pre-complexed heparin:VEGF adsorbed non-specifically, with no distinguish between non-specific adsorption and heparin guided-adsorption. On the biological side, heparin guided-adsorption of Heparin:VEGF enhanced HUVECs surface coverage as compared to non-specific adsorption. These results provide a detailed insight on the molecular sandwich which is useful for new design strategies of supramolecular biomaterials with well-controlled immobilization of different growth factors.</p

Spin asymmetry A_1^d and the spin-dependent structure function g_1^d of the deuteron at low values of x and Q^2

We present a precise measurement of the deuteron longitudinal spin asymmetry A_1^d and of the deuteron spin-dependent structure function g_1^d at Q^2 < 1 GeV^2 and 4*10^-5 < x < 2.5*10^-2 based on the data collected by the COMPASS experiment at CERN during the years 2002 and 2003. The statistical precision is tenfold better than that of the previous measurement in this region. The measured A_1^d and g_1^d are found to be consistent with zero in the whole range of x.Comment: 17 pages, 10 figure

Measurement of the open-charm contribution to the diffractive proton structure function

Production of D*+/-(2010) mesons in diffractive deep inelastic scattering has been measured with the ZEUS detector at HERA using an integrated luminosity of 82 pb^{-1}. Diffractive events were identified by the presence of a large rapidity gap in the final state. Differential cross sections have been measured in the kinematic region 1.5 < Q^2 < 200 GeV^2, 0.02 < y < 0.7, x_{IP} < 0.035, beta 1.5 GeV and |\eta(D*+/-)| < 1.5. The measured cross sections are compared to theoretical predictions. The results are presented in terms of the open-charm contribution to the diffractive proton structure function. The data demonstrate a strong sensitivity to the diffractive parton densities.Comment: 35 pages, 11 figures, 6 table

Forward jet production in deep inelastic ep scattering and low-x parton dynamics at HERA

Differential inclusive jet cross sections in neutral current deep inelastic ep scattering have been measured with the ZEUS detector. Three phase-space regions have been selected in order to study parton dynamics where the effects of BFKL evolution might be present. The measurements have been compared to the predictions of leading-logarithm parton shower Monte Carlo models and fixed-order perturbative QCD calculations. In the forward region, QCD calculations at order alpha_s^1 underestimate the data up to an order of magnitude at low x. An improved description of the data in this region is obtained by including QCD corrections at order alpha_s^2, which account for the lowest-order t-channel gluon-exchange diagrams, highlighting the importance of such terms in parton dynamics at low x.Comment: 25 pages, 4 figure

Deep inelastic inclusive and diffractive scattering at Q2Q^2 values from 25 to 320 GeV2^2 with the ZEUS forward plug calorimeter

Deep inelastic scattering and its diffractive component, $ep \to e^{\prime}\gamma^* p \to e^{\prime}XN$, have been studied at HERA with the ZEUS detector using an integrated luminosity of 52.4 pb$^{-1}$. The $M_X$ method has been used to extract the diffractive contribution. A wide range in the centre-of-mass energy $W$ (37 -- 245 GeV), photon virtuality $Q^2$ (20 -- 450 GeV$^2$) and mass $M_X$ (0.28 -- 35 GeV) is covered. The diffractive cross section for $2 < M_X < 15$ GeV rises strongly with $W$, the rise becoming steeper as $Q^2$ increases. The data are also presented in terms of the diffractive structure function, $F^{\rm D(3)}_2$, of the proton. For fixed $Q^2$ and fixed $M_X$, \xpom F^{\rm D(3)}_2 shows a strong rise as \xpom \to 0, where \xpom is the fraction of the proton momentum carried by the Pomeron. For Bjorken-$x < 1 \cdot 10^{-3}$, \xpom F^{\rm D(3)}_2 shows positive $\log Q^2$ scaling violations, while for $x \ge 5 \cdot 10^{-3}$ negative scaling violations are observed. The diffractive structure function is compatible with being leading twist. The data show that Regge factorisation is broken.Comment: 89 pages, 27 figure

Multiplicity dependence of inclusive J/psi production at midrapidity in pp collisions at root s=13 TeV

Measurements of the inclusive J/psi yield as a function of charged-particle pseudorapidity density dN(ch)/d eta in pp collisions at root s = 13 TeV with ALICE at the LHC are reported. The J/psi meson yield is measured at midrapidity (vertical bar y vertical bar <0.9) in the dielectron channel, for events selected based on the charged-particle multiplicity at midrapidity (vertical bar eta vertical bar <1) and at forward rapidity (-3.7 <eta <-1.7 and 2.8 <eta <5.1); both observables are normalized to their corresponding averages in minimum bias events. The increase of the normalized J/psi yield with normalized dN(ch)/d eta is significantly stronger than linear and dependent on the transverse momentum. The data are compared to theoretical predictions, which describe the observed trends well, albeit not always quantitatively. (C) 2020 European Organization for Nuclear Research. Published by Elsevier B.V.Peer reviewe

First measurement of Ωc0 production in pp collisions at s=13 TeV

The inclusive production of the charm–strange baryon 0 c is measured for the first time via its hadronic √ decay into −π+ at midrapidity (|y| &lt;0.5) in proton–proton (pp) collisions at the centre-of-mass energy s =13 TeV with the ALICE detector at the LHC. The transverse momentum (pT) differential cross section multiplied by the branching ratio is presented in the interval 2 &lt; pT &lt; 12 GeV/c. The pT dependence of the 0 c-baryon production relative to the prompt D0-meson and to the prompt 0 c-baryon production is compared to various models that take different hadronisation mechanisms into consideration. In the measured pT interval, the ratio of the pT-integrated cross sections of 0 c and prompt + c baryons multiplied by the −π+ branching ratio is found to be larger by a factor of about 20 with a significance of about 4σ when compared to e+e− collisions

Bioinspired Silk Fibroin Mineralization for Advanced In Vitro Bone Remodeling Models

Human in vitro bone models can create the possibility for investigation of physiological bone remodeling while addressing the principle of replacement, reduction and refinement of animal experiments (3R). Current in vitro models lack cell–matrix interactions and their spatiotemporal complexity. To facilitate these analyses, a bone-mimetic template is developed in this study, inspired by bone's extracellular matrix composition and organization. Silk fibroin (SF) is used as an organic matrix, poly-aspartic acid (pAsp) is used to mimic the functionality of noncollagenous proteins, and 10× simulated body fluid serves as mineralization solution. By using pAsp in the mineralization solution, minerals are guided toward the SF material resulting in mineralization inside and as a coating on top of the SF. After cytocompatibility testing, remodeling experiments are performed in which mineralized scaffold remodeling by osteoclasts and osteoblasts is tracked with nondestructive microcomputed tomography and medium analyses over a period of 42 d. The mineralized scaffolds support osteoclastic resorption and osteoblastic mineralization, in the physiological bone remodeling specific sequence. This model could therefore facilitate the investigation of cell–matrix interactions and may thus reduce animal experiments and advance in vitro drug testing for bone remodeling pathologies like osteoporosis, where cell–matrix interactions need to be targeted

Supramolecular Additive-Initiated Controlled Atom Transfer Radical Polymerization of Zwitterionic Polymers on Ureido-pyrimidinone-Based Biomaterial Surfaces

Surface-initiated controlled radical polymerization is a popular technique for the modification of biomaterials with, for example, antifouling polymers. Here, we report on the functionalization of a supramolecular biomaterial with zwitterionic poly(sulfobetaine methacrylate) via atom transfer radical polymerization from a macroinitiator additive, which is embedded in the hard phase of the ureido-pyrimidinone-based material. Poly(sulfobetaine methacrylate) was successfully polymerized from these surfaces, and the polymerized sulfobetaine content, with corresponding antifouling properties, depended on both the macroinitiator additive concentration and polymerization time. Furthermore, the polymerization from the macroinitiator additive was successfully translated to functional electrospun scaffolds, showing the potential for this functionalization strategy in supramolecular material systems. ©</p