Comparison of the adsorption of linear and cyclic antimicrobial peptides onto cellulosic compounds-reinforced poly(vinyl alcohol) films using QCM-D

Understanding peptide adsorption kinetics onto biomaterial surfaces is crucial for developing wound treatments. This study aims to explore the influence of cellulose acetate (CA) and cellulose nanocrystals (CNC) on peptide adsorption via quartz crystal microbalance with dissipation monitoring (QCM-D), using a cyclic peptide, Tiger 17, and a linear, Pexiganan. PVA was reinforced with 10 and 20% w/v of CA and CNC, spin-coated onto QCM-D sensors, and crosslinked with glutaraldehyde. Films containing higher percentages of cellulosic compounds promoted the highest peptide adsorption, with CNC-containing films being the most effective. While C80/20 PVA/CNC films achieved adsorption masses of ≈199 and ≈150 ng/cm2 for Tiger 17 and Pexiganan, respectively, the C80/20 PVA/CA films attained ≈168 and ≈122 ng/cm2 . The peptides’ structure also influenced adsorption, with Tiger 17 reaching greater frequency drops (ΔF) than Pexiganan. Sequential adsorption studies corroborated these findings. Even though the tendency was for PVA/CNC to promote the highest peptide binding, it was the PVA/CA films that reached the greatest peptide loading amount with the sequence Pexiganan + Tiger 17. Data are encouraging for developing new wound therapies reinforced with cellulosic compounds and modified with Tiger 17 and Pexiganan.Authors acknowledge the Portuguese Foundation for Science and Technology (FCT), Fulbright Scholarship Program, FEDER funds by means of Portugal 2020 Competitive Factors Operational Program (POCI) and the Portuguese Government (OE) for funding the project with reference PTDC/CTM-TEX/28074/2017 (POCI-01–0145-FEDER028074). Authors also acknowledge project UID/CTM/00264/2020 of Centre for Textile Science and Technology (2C2T) on its components base (https://doi.org/10.54499/UIDB/00264/2020) and programmatic (https://doi.org/10.54499/UIDP/00264/2020). M.A.T., D.P.F and H.P. F. acknowledge FCT for PhD scholarship (SFRH/BD/148930/2019) and junior (CEECIND/02803/2017) and auxiliary researcher(2021.02720. CEECIND; https://doi.org/10.54499/DL57/2016/CP1377/CT0098) contracts, respectively

Enhancement of plasma protein adsorption and osteogenesis of hMSCs by functionalized siloxane coatings for titanium implants

A series of sol–gel derived silicon based coatings were developed to improve the osseointegration of commer- cial titanium dental implants. The osseointegration starts with a positive interaction between the implant surface and surrounding tissues, which is facilitated by the adsorption of plasma proteins onto the biomaterial surface immediately after implantation. It is likely that the enhancement of protein adsorption to titanium implants leads to a better implant/tis- sue integration. In addition, silica based biomaterials have been shown to promote osteoblast differentiation. To improve the protein adsorption and the osteogenesis, meth- yltrimethoxysilane (MTMOS), tetraethoxysilane (TEOS), 3- glycidoxypropyltrimethoxysilane (GPTMS), and gelatin were selected to coat titanium surfaces. Compared with non- coated titanium, the functionalized coatings enhanced the adsorption of adhesive proteins such as fibronectin and colla- gen. The Si release was successfully modulated by the con- trol of the chemical composition of the coating, showing a higher dissolution rate with the gelatin and GPTMS incorpo- ration. While the roughness of commercial implants seemed to promote the adhesion of mesenchymal stem cells (MSC), the osteogenic differentiation was greater on surfaces with Si-coatings. In this study, an improved osteogenic surface has been achieved by using the siloxane-gelatin coatings and such coatings can be used in dental implants to promote osseointegration

Carbohydrate-derived amphiphilic macromolecules: a biophysical structural characterization and analysis of binding behaviors to model membranes.

The design and synthesis of enhanced membrane-intercalating biomaterials for drug delivery or vascular membrane targeting is currently challenged by the lack of screening and prediction tools. The present work demonstrates the generation of a Quantitative Structural Activity Relationship model (QSAR) to make a priori predictions. Amphiphilic macromolecules (AMs) "stealth lipids" built on aldaric and uronic acids frameworks attached to poly(ethylene glycol) (PEG) polymer tails were developed to form self-assembling micelles. In the present study, a defined set of novel AM structures were investigated in terms of their binding to lipid membrane bilayers using Quartz Crystal Microbalance with Dissipation (QCM-D) experiments coupled with computational coarse-grained molecular dynamics (CG MD) and all-atom MD (AA MD) simulations. The CG MD simulations capture the insertion dynamics of the AM lipophilic backbones into the lipid bilayer with the PEGylated tail directed into bulk water. QCM-D measurements with Voigt viscoelastic model analysis enabled the quantitation of the mass gain and rate of interaction between the AM and the lipid bilayer surface. Thus, this study yielded insights about variations in the functional activity of AM materials with minute compositional or stereochemical differences based on membrane binding, which has translational potential for transplanting these materials in vivo. More broadly, it demonstrates an integrated computational-experimental approach, which can offer a promising strategy for the in silico design and screening of therapeutic candidate materials

Temperature-Activated PEG Surface Segregation Controls the Protein Repellency of Polymers

Poly(ethylene glycol) (PEG) is widely used to modulate the hydration states of biomaterials and is often applied to produce nonfouling surfaces. Here, we present X-ray scattering data, which show that it is the surface segregation of PEG, not just its presence in the bulk, that makes this happen by influencing the hydrophilicity of PEG-containing substrates. We demonstrate a temperature-dependent trigger that transforms a PEG-containing substrate from a protein-adsorbing to a protein-repelling state. On films of poly(desaminotyrosyl-tyrosine-co-PEG carbonate) with high (20 wt %) PEG content, in which very little protein adsorption is expected, quartz crystal microbalance data showed significant adsorption of fibrinogen and bovine serum albumin at 8 °C. The surface became protein-repellent at 37.5 °C. When the same polymer was iodinated, the polymer was protein-adsorbent, even when 37 wt % PEG was incorporated into the polymer backbone. This demonstrates that high PEG content by itself is not sufficient to repel proteins. By inhibiting phase separation either with iodine or by lowering the temperature, we show that PEG must phase-separate and bloom to the surface to create an antifouling surface. These results suggest an opportunity to design materials with high PEG content that can be switched from a protein-attractant to a protein-repellent state by inducing phase separation through brief exposure to temperatures above their glass transition temperature

Elliptical Small-Angle X-Ray Scattering Patterns from Aligned Lamellar Arrays

Semicrystalline polymers aligned by drawing into films or fibers produce small-angle X-ray scattering patterns with two or four spots. Some liquid crystalline materials, cybotactic nematics, produce extremely similar patterns when oriented in magnetic fields. A structure of stacked lamellae, tilted for four point patterns, explain the basic features. However, the peak intensity positions of the broadened reflections lie not on a layer line or on the arc of a circle, but very close to an ellipse. Specific structural explanations of this feature have been suggested, but models using an equilibrium distribution of molecular orientations and lamellar tilts can predict elliptical shapes for the reflections. The model parameters are chosen by fitting the entire 2D intensity distribution of the scattering pattern. Assumptions required for modeling make some fitted parameters uncertain, but it is clear that the elliptical form can emerge from a statistical distribution of the properties of the stacks of lamellae, without a directly assignable structural cause

Hydration-Induced Phase Separation in Amphiphilic Polymer Matrices and its Influence on Voclosporin Release

Voclosporin is a highly potent, new cyclosporine-A derivative that is currently in Phase 3 clinical trials in the USA as a potential treatment for inflammatory diseases of the eye. Voclosporin represents a number of very sparingly soluble drugs that are difficult to administer. We therefore selected it as a model drug that is dispersed within amphiphilic polymer matrices, and investigated the changing morphology of the matrices using neutron and x-ray scattering during voclosporin release and polymer resorption. The hydrophobic segments of the amphiphilic polymer chain are comprised of desaminotyrosyl-tyrosine ethyl ester (DTE) and desaminotyrosyl-tyrosine (DT), and the hydrophilic component is poly(ethylene glycol) (PEG). Water uptake in these matrices resulted in the phase separation of hydrophobic and hydrophilic domains that are a few hundred Angstroms apart. These water-driven morphological changes influenced the release profile of voclosporin and facilitated a burst-free release from the polymer. No such morphological reorganization was observed in poly(lactide-co-glycolide) (PLGA), which exhibits an extended lag period, followed by a burst-like release of voclosporin when the polymer was degraded. An understanding of the effect of polymer composition on the hydration behavior is central to understanding and controlling the phase behavior and resorption characteristics of the matrix for achieving long-term controlled release of hydrophobic drugs such as voclosporin

Crystal Structure and Properties of N6/AMCC Copolymer from Theory and Fiber XRD

The MSXX force field developed previously from ab initio quantum calculations for studies of nylon are used to study the crystal structure and properties of the copolymer of nylon 6 with AMCC (4-aminomethylcyclohexanecarboxylic acid). For the isolated chain conformation of the copolymer, we consider both axial and equatorial connections of the chain with the cyclohexane ring and find that the best is chair-ee-St, which has equatorial connections on both ends of chair cyclohexane. We consider 12 possible crystal structures for the copolymer (the best four conformations of the isolated chain with the three forms of packing these chains:  α form, γ form, and δ form). With 12.5% of AMCC in the copolymer, we find that the γ form with the chair-ee-St chain structure is the most stable, even though the α form is most stable for nylon 6. The calculated X-ray diffraction patterns of the predicted crystal structure fit both equatorial and meridional scans of XRD very well. There are two reasons that make α form less stable for the copolymer. One is the bad contact between the axial hydrogen atoms of the cyclohexane ring and the CH2 hydrogens. The other is the difficulty of intramolecular H-bonds in the copolymer. The predicted chain-axis repeat distance of the copolymer (0 K) is 1.4 Å smaller than for the α form of Nylon 6, in good agreement with the X-ray results, which indicates that it is 1.5 Å smaller (at 300 K). Young's modulus in the chain direction is calculated to be 93 GPa for the copolymer (at 0 K), which compares to 135 and 295 GPa predicted for γ form and α form nylon 6, respectively. The introduced cyclohexane ring locates between the two amide pockets of the adjacent hydrogen bond sheets and has two major effects on the properties of the copolymer:  (i) It causes twisted conformations, which decreases Young's modulus of the copolymer in chain direction. (ii) It makes the chain rigid, which likely is responsible for the decrease in sensitivity of the copolymer to moisture