Assessment of Linear and Cyclic Peptides' Immobilization onto Cross-Linked, Poly(vinyl alcohol)/Cellulose Nanocrystal Nanofibers Electrospun over Quartz Crystal Microbalances with Dissipation Sensors.

Immobilization of peptides onto nanofiber dressings holds significant potential for chronic wound treatment. However, it is necessary to understand the adsorptive capacity of the produced substrates and the binding affinity of the peptides to determine the interface success. This study aims at exploring for the first time the influence of electrospun poly(vinyl alcohol)-based nanofibers on the adsorption of a cyclic peptide, Tiger 17, and of a linear peptide, Pexiganan, using quartz crystal microbalance with dissipation monitoring (QCM-D).

Phosphorylation Toggles the SARS-CoV-2 Nucleocapsid Protein Between Two Membrane-Associated Condensate States.

The SARS-CoV-2 Nucleocapsid protein (N) performs several functions during the viral lifecycle, including transcription regulation and viral genome encapsulation. We hypothesized that N toggles between these functions via phosphorylation-induced conformational change, thereby altering N interactions with membranes and RNA. We found that phosphorylation changes how biomolecular condensates composed of N and RNA interact with membranes: phosphorylated N (pN) condensates form thin films, while condensates with unmodified N are engulfed.

Evolution of elliptical SAXS patterns in aligned systems.

Small-angle X-ray and neutron scattering (SAXS and SANS) patterns from certain semicrystalline polymers and liquid crystals contain discrete reflections from ordered assemblies and central diffuse scattering (CDS) from uncorrelated structures. Systems with imperfectly ordered lamellar structures aligned by stretching or by a magnetic field produce four distinct SAXS patterns: two-point 'banana', four-point pattern, four-point 'eyebrow' and four-point 'butterfly'. The peak intensities of the reflections lie not on a layer line, or the arc of a circle, but on an elliptical trajectory.

Biomimetic Strategies for Peripheral Nerve Injury Repair: An Exploration of Microarchitecture and Cellularization.

Injuries to the nervous system present formidable challenges to scientists, clinicians, and patients. While regeneration within the central nervous system is minimal, peripheral nerves can regenerate, albeit with limitations. The regenerative mechanisms of the peripheral nervous system thus provide fertile ground for clinical and scientific advancement, and opportunities to learn fundamental lessons regarding nerve behavior in the context of regeneration, particularly the relationship of axons to their support cells and the extracellular matrix environment.

Asymmetrical interactions between nanoparticles and proteins arising from deformation upon adsorption to surfaces.

Drug release from polymeric nanoparticles (NPs) is governed by their adsorption onto cell membranes and transmigration across cell walls. These steps are influenced by their interactions with proteins near the cells. These interactions were investigated by studying the sequential adsorption of plasma proteins, albumin (Alb) and fibrinogen (Fg), and micellar NPs using quartz crystal microbalance with dissipation (QCMD), X-ray photoelectron spectroscopy (XPS), and small-angle X-ray scattering (SAXS).

Examining polymer-protein biophysical interactions with small-angle x-ray scattering and quartz crystal microbalance with dissipation.

Polymer-protein hybrids can be deployed to improve protein solubility and stability in denaturing environments. While previous work used robotics and active machine learning to inform new designs, further biophysical information is required to ascertain structure-function behavior. Here, we show the value of tandem small-angle x-ray scattering (SAXS) and quartz crystal microbalance with dissipation (QCMD) experiments to reveal detailed polymer-protein interactions with horseradish peroxidase (HRP) as a test case.

Polymer Texture Influences Cell Responses in Osteogenic Microparticles.

Introduction: Polymer materials used in medical devices and treatments invariably encounter cellular networks. For the device to succeed in tissue engineering applications, the polymer must promote cellular interactions through adhesion and proliferation. To predict how a polymer will behave , these material-cell interactions need to be well understood.

Axonal Tract Reconstruction Using a Tissue-Engineered Nigrostriatal Pathway in a Rat Model of Parkinson's Disease.

Parkinson's disease (PD) affects 1-2% of people over 65, causing significant morbidity across a progressive disease course. The classic PD motor deficits are caused by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in the loss of their long-distance axonal projections that modulate striatal output. While contemporary treatments temporarily alleviate symptoms of this disconnection, there is no approach able to replace the nigrostriatal pathway.

Iodination of PEGylated Polymers Counteracts the Inhibition of Fibrinogen Adsorption by PEG.

Poly(ethylene glycol), PEG, known to inhibit protein adsorption, is widely used on the surfaces of biomedical devices when biofilm formation is undesirable. Poly(desaminotyrosyl-tyrosine ethyl ester carbonate), PDTEC, PC for short, has been a promising coating polymer for insertion devices, and it has been anticipated that PEG plays a similar role if it is copolymerized with PC. Earlier studies show that no fibrinogen (Fg) is adsorbed onto PC polymers with PEG beyond the threshold weight percentage.

Machine Learning on a Robotic Platform for the Design of Polymer-Protein Hybrids.

Polymer-protein hybrids are intriguing materials that can bolster protein stability in non-native environments, thereby enhancing their utility in diverse medicinal, commercial, and industrial applications. One stabilization strategy involves designing synthetic random copolymers with compositions attuned to the protein surface, but rational design is complicated by the vast chemical and composition space. Here, a strategy is reported to design protein-stabilizing copolymers based on active machine learning, facilitated by automated material synthesis and characterization platforms.

Thermal Processing of a Degradable Carboxylic Acid-Functionalized Polycarbonate into Scaffolds for Tissue Engineering.

Degradable polymers are often desirable for the fabrication of medical implants, but thermal processing of these polymers is a challenge. We describe here how these problems can be addressed by discussing the extrusion of fibers and injection molding of bone pins from a hydrolytically degradable tyrosine-derived polycarbonate. Our initial attempts produced fibers and pins with bubbles, voids, and discoloration, and resulted in the formation of large polymer plugs that seized screws and blocked extruder dies.

Tyrosine-derived polycarbonate nerve guidance tubes elicit proregenerative extracellular matrix deposition when used to bridge segmental nerve defects in swine.

Promising biomaterials should be tested in appropriate large animal models that recapitulate human inflammatory and regenerative responses. Previous studies have shown tyrosine-derived polycarbonates (TyrPC) are versatile biomaterials with a wide range of applications across multiple disciplines. The library of TyrPC has been well studied and consists of thousands of polymer compositions with tunable mechanical characteristics and degradation and resorption rates that are useful for nerve guidance tubes (NGTs).

Calcium phosphate enriched synthetic tyrosine-derived polycarbonate - dicalcium phosphate dihydrate polymer scaffolds for enhanced bone regeneration.

Optimal repair of large craniomaxillofacial (CMF) defects caused by trauma or disease requires the development of new, synthetic osteoconductive materials in combination with cell-based therapies, to overcome the limitations of traditionally used bone graft substitutes. In this study, tyrosine-derived polycarbonate, E1001(1k) scaffolds were fabricated to incorporate the osteoinductive coating, Dicalcium phosphate dihydrate (DCPD). The biocompatibility of E1001(1k)-DCPD, E1001(1k)-βTCP and E1001(1k) scaffolds was compared using culture with human dental pulp stem cells (hDPSCs).

A multilayered scaffold for regeneration of smooth muscle and connective tissue layers.

Tissue regeneration often requires recruitment of different cell types and rebuilding of two or more tissue layers to restore function. Here, we describe the creation of a novel multilayered scaffold with distinct fiber organizations-aligned to unaligned and dense to porous-to template common architectures found in adjacent tissue layers. Electrospun scaffolds were fabricated using a biodegradable, tyrosine-derived terpolymer, yielding densely-packed, aligned fibers that transition into randomly-oriented fibers of increasing diameter and porosity.

Disassembly of Nanospheres with a PEG Shell upon Adsorption onto PEGylated Substrates.

Polymeric nanospheres have the ability to encapsulate drugs and are therefore widely used in drug delivery applications. Structural transformations that affect drug release from nanospheres are governed by the surrounding environment. To understand these effects, we investigated the adsorption behavior of three types of nanospheres onto model surfaces using quartz crystal microbalance with dissipation (QCM-D) and by atomic force microscopy (AFM).

A step toward engineering thick tissues: Distributing microfibers within 3D printed frames.

Microfiber mats for tissue engineering scaffolds support cell growth, but are limited by poor cell infiltration and nutrient transport. Three-dimensional printing, specifically fused deposition modeling (FDM), can rapidly produce customized constructs, but macroscopic porosity resulting from low resolution reduces cell seeding efficiency and prevents the formation of continuous cell networks. Here we describe the fabrication of hierarchical scaffolds that integrate a fibrous microenvironment with the open macropore structure of FDM.

PET-RAFT and SAXS: High Throughput Tools to Study Compactness and Flexibility of Single-Chain Polymer Nanoparticles.

From protein science, it is well understood that ordered folding and 3D structure mainly arises from balanced and noncovalent polar and nonpolar interactions, such as hydrogen bonding. Similarly, it is understood that single-chain polymer nanoparticles (SCNPs) will also compact and become more rigid with greater hydrophobicity and intrachain hydrogen bonding. Here, we couple high throughput photoinduced electron/energy transfer reversible addition-fragmentation chain-transfer (PET-RAFT) polymerization with high throughput small-angle X-ray scattering (SAXS) to characterize a large combinatorial library (>450) of several homopolymers, random heteropolymers, block copolymers, PEG-conjugated polymers, and other polymer-functionalized polymers.

Crystal structure and Hirshfeld surface analysis of 2-(4-nitro-phen-yl)-2-oxoethyl picolinate.

2-(4-Nitro-phen-yl)-2-oxoethyl picolinate, CHNO, was synthesized under mild conditions. The chemical and mol-ecular structures were confirmed by single-crystal X-ray diffraction analysis. The mol-ecules are linked by inversion into centrosymmetric dimers weak inter-molecular C-H⋯O inter-actions, forming (10) ring motifs, and further strengthened by weak π-π inter-actions.

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.

Adsorption of Fibrinogen and Fibronectin on Elastomeric Poly(butylene succinate) Copolyesters.

Proteins adsorbed onto biomaterial surfaces facilitate cell-material interactions, including adhesion and migration. Of particular importance are provisional matrix components, fibrinogen (Fg) and fibronectin (Fn), which play an important role in the wound-healing process. Here, to assess the potential of a series of elastomeric poly(butylene succinate) (PBS) copolymers for soft tissue engineering and regenerative medicine applications, we examined the adsorption of Fg and Fn.

Achieving molecular orientation in thermally extruded 3D printed objects.

Three-dimensional (3D) printing is used to fabricate tissue scaffolds. Polymer chains in these objects are typically unoriented. The mechanical properties of these scaffolds can be significantly enhanced by proper alignment of polymer chains.

Structure of intermediate filament assembly in hair deduced from hydration studies using small-angle neutron scattering.

Intermediate filaments (IFs) are ubiquitous in biological structures including hair. Small-angle neutron scattering (SANS) data from hydrated samples were used in this study to investigate the distribution of water in hair, and model the structure of the IF assembly. A main diffraction peak at a d-spacing of ∼90 Å, and two weaker reflections show that IFs are arranged in a ∼105 Å quasi-hexagonal lattice.

A method to deliver patterned electrical impulses to Schwann cells cultured on an artificial axon.

Information from the brain travels back and forth along peripheral nerves in the form of electrical impulses generated by neurons and these impulses have repetitive patterns. Schwann cells in peripheral nerves receive molecular signals from axons to coordinate the process of myelination. There is evidence, however, that non-molecular signals play an important role in myelination in the form of patterned electrical impulses generated by neuronal activity.

Crystal structure and Hirshfeld surface analysis of ()-3-(2-chloro-4-fluoro-phen-yl)-1-(2,5-di-chloro-thio-phen-3-yl)prop-2-en-1-one.

In the title chalcone-thio-phene derivative, CHClFOS, the aromatic rings are inclined to one another by 12.9 (2)°, and the thio-phene ring is affected by π-conjugation. In the crystal, mol-ecules are linked by C-H⋯F hydrogen bonds, forming an (8) ring motif.

Substrate micropatterns produced by polymer demixing regulate focal adhesions, actin anisotropy, and lineage differentiation of stem cells.

Unlabelled: Stem cells are adherent cells whose multipotency and differentiation can be regulated by numerous microenvironmental signals including soluble growth factors and surface topography. This study describes a simple method for creating distinct micropatterns via microphase separation resulting from polymer demixing of poly(desaminotyrosyl-tyrosine carbonate) (PDTEC) and polystyrene (PS). Substrates with co-continuous (ribbons) or discontinuous (islands and pits) PDTEC regions were obtained by varying the ratio of PDTEC and sacrificial PS.