Foreign Body Immune Response to Zwitterionic and Hyaluronic Acid Granular Hydrogels Made with Mechanical Fragmentation.

Granular hydrogels have recently attracted the attention for diverse tissue engineering applications due to their versatility and modularity. Despite previous studies showing enhanced viability and metabolism of cells encapsulated in these hydrogels, the in vitro immune response and long-term fibrotic response of these scaffolds have not been well characterized. Here, bulk and granular hydrogels are studied based on synthetic zwitterionic (ZI) and natural polysaccharide hyaluronic acid (HA) made with mechanical fragmentation.

FLight Biofabrication Supports Maturation of Articular Cartilage with Anisotropic Properties.

Tissue engineering approaches that recapitulate cartilage biomechanical properties are emerging as promising methods to restore the function of injured or degenerated tissue. However, despite significant progress in this research area, the generation of engineered cartilage constructs akin to native counterparts still represents an unmet challenge. In particular, the inability to accurately reproduce cartilage zonal architecture with different collagen fibril orientations is a significant limitation.

Growth factor-loaded sulfated microislands in granular hydrogels promote hMSCs migration and chondrogenic differentiation.

Cell-based therapies for articular cartilage lesions are expensive and time-consuming; clearly, a one-step procedure to induce endogenous repair would have significant clinical benefits. Acellular heterogeneous granular hydrogels were explored for their injectability, cell-friendly cross-linking, and ability to promote migration, as well as to serve as a scaffold for depositing cartilage extracellular matrix. The hydrogels were prepared by mechanical sizing of bulk methacrylated hyaluronic acid (HAMA) and bulk HAMA incorporating sulfated HAMA (SHAMA).

Cartilage tissue engineering by extrusion bioprinting utilizing porous hyaluronic acid microgel bioinks.

3D bioprinting offers an excellent opportunity to provide tissue-engineered cartilage to microtia patients. However, hydrogel-based bioinks are hindered by their dense and cell-restrictive environment, impairing tissue development and ultimately leading to mechanical failure of large scaffolds. Granular hydrogels, made of annealed microgels, offer a superior alternative to conventional bioinks, with their improved porosity and modularity.

Hybrid conducting alginate-based hydrogel for hydrogen peroxide detection from enzymatic oxidation of lactate.

A conducting nanocomposite hydrogel is developed for the detection of L-lactate. The hydrogel is based on a mixture of alginate (Alg) and poly(3,4-ethylenedioxythiophene) (PEDOT), which is loaded with gold nanoparticles (GNP). In this novel hydrogel, Alg provides 3D structural support and flexibility, PEDOT confers conductivity and sensing capacity, and GNP provides signal amplification with respect to simple voltammetric and chronoamperometric response.

Remote Spatiotemporal Control of a Magnetic and Electroconductive Hydrogel Network via Magnetic Fields for Soft Electronic Applications.

Multifunctional hydrogels are a class of materials offering new opportunities for interfacing living organisms with machines due to their mechanical compliance, biocompatibility, and capacity to be triggered by external stimuli. Here, we report a dual magnetic- and electric-stimuli-responsive hydrogel with the capacity to be disassembled and reassembled up to three times through reversible cross-links. This allows its use as an electronic device (e.

Self-standing, conducting and capacitive biomimetic hybrid nanomembranes for selective molecular ion separation.

Hybrid free-standing biomimetic materials are developed by integrating the VDAC36 β-barrel protein into robust and flexible three-layered polymer nanomembranes. The first and third layers are prepared by spin-coating a mixture of poly(lactic acid) (PLA) and poly(vinyl alcohol) (PVA). PVA nanofeatures are transformed into controlled nanoperforations by solvent-etching.

Green Nanocoatings Based on the Deposition of Zirconium Oxide: The Role of the Substrate.

Herein, the influence of the substrate in the formation of zirconium oxide monolayer, from an aqueous hexafluorozirconic acid solution, by chemical conversion and by electro-assisted deposition, has been approached. The nanoscale dimensions of the ZrO film is affected by the substrate nature and roughness. This study evidenced that the mechanism of Zr-EAD is dependent on the potential applied and on the substrate composition, whereas conversion coating is uniquely dependent on the adsorption reaction time.

Conducting polymer nanoparticles for a voltage-controlled release of pharmacological chaperones.

Pharmacological chaperones (PCs) are low-molecular weight chemical molecules used in patients for the treatment of some rare diseases caused primarily by protein instability. A controlled and on-demand release of PCs via nanoparticles is an alternative for cases in which long treatments are needed and prolonged oral administration could have adverse effects. In this work, pyrimethamine (PYR), which is a potent PC consisting of pyrimidine-2,4-diamine substituted at position 5 by a p-chlorophenyl group and at position 6 by an ethyl group, was successfully loaded in electroresponsive poly(3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs).

Encapsulation and Storage of Therapeutic Fibrin-Homing Peptides using Conducting Polymer Nanoparticles for Programmed Release by Electrical Stimulation.

Cys-Arg-Glu-Lys-Ala (CREKA) is an important fibrin-homing pentapeptide that has been extensively demonstrated for diagnoses and therapies (e.g., image diagnosis of tumors and to inhibit tumor cell migration and invasion).

Electroresponsive Alginate-Based Hydrogels for Controlled Release of Hydrophobic Drugs.

Stimuli-responsive biomaterials have attracted significant attention for the construction of on-demand drug release systems. The possibility of using external stimulation to trigger drug release is particularly enticing for hydrophobic compounds, which are not easily released by simple diffusion. In this work, an electrochemically active hydrogel, which has been prepared by gelling a mixture of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) and alginate (Alg), has been loaded with curcumin (CUR), a hydrophobic drug with a wide spectrum of clinical applications.

Tuning multilayered polymeric self-standing films for controlled release of L-lactate by electrical stimulation.

We examine different approaches for the controlled release of L-lactate, which is a signaling molecule that participates in tissue remodeling and regeneration, such as cardiac and muscle tissue. Robust, flexible, and self-supported 3-layers films made of two spin-coated poly(lactic acid) (PLA) layers separated by an electropolymerized poly(3,4-ethylenedioxythiophene) (PEDOT) layer, are used as loading and delivery systems. Films with outer layers prepared using homochiral PLA and with nanoperforations of diameter 146 ± 70 experience more bulk erosion, which also contributes to the release of L-lactic acid, than those obtained using heterochiral PLA and with nanoperforations of diameter 66 ± 24.

Nanotheranostic Interface Based on Antibiotic-Loaded Conducting Polymer Nanoparticles for Real-Time Monitoring of Bacterial Growth Inhibition.

Conducting polymers have been increasingly used as biologically interfacing electrodes for biomedical applications due to their excellent and fast electrochemical response, reversible doping-dedoping characteristics, high stability, easy processability, and biocompatibility. These advantageous properties can be used for the rapid detection and eradication of infections associated to bacterial growth since these are a tremendous burden for individual patients as well as the global healthcare system. Herein, a smart nanotheranostic electroresponsive platform, which consists of chloramphenicol (CAM)-loaded in poly(3,4-ethylendioxythiophene) nanoparticles (PEDOT/CAM NPs) for concurrent release of the antibiotic and real-time monitoring of bacterial growth is presented.

Effect of conducting/thermoresponsive polymer ratio on multitasking nanogels.

Semi-interpenetrated nanogels (NGs) able to release and sense diclofenac (DIC) have been designed to act as photothermal agents with the possibility to ablate cancer cells using mild-temperatures (<45 °C). Combining mild heat treatments with simultaneous chemotherapy appears as a very promising therapeutic strategy to avoid heat resistance or damaging the surrounding tissues. Particularly, NGs consisted on a poly(N-isopropylacrylamide) (PNIPAM) and dendritic polyglycerol (dPG) mesh containing a semi-interpenetrating network (SIPN) of poly(hydroxymethyl 3,4-ethylenedioxythiophene) (PHMeEDOT).

Aggregation propensity of therapeutic fibrin-homing pentapeptides: insights from experiments and molecular dynamics simulations.

CREKA (Cys-Arg-Glu-Lys-Ala) and its engineered analogue CRMeEKA, in which Glu has been replaced by N-methyl-Glu to provide resistance against proteolysis, are emerging pentapeptides that were specifically designed to bind fibrin-fibronectin complexes accumulated in the walls of tumour vessels. However, many of the intrinsic properties of CREKA and CRMeEKA, which are probably responsible for their different behaviour when combined with other materials (such as polymers) for diagnosis and therapeutics, remain unknown yet. The intrinsic tendency of these pentapeptides to form aggregates has been analysed by combining experimental techniques and atomistic Molecular Dynamics (MD) simulations.

Properties of Omp2a-Based Supported Lipid Bilayers: Comparison with Polymeric Bioinspired Membranes.

Omp2a β-barrel outer membrane protein has been reconstituted into supported lipid bilayers (SLBs) to compare the nanomechanical properties (elastic modulus, adhesion forces, and deformation) and functionality of the resulting bioinspired system with those of Omp2a-based polymeric nanomembranes (NMs). Protein reconstitution into lipid bilayers has been performed using different strategies, the most successful one consisting of a detergent-mediated process into preformed liposomes. The elastic modulus obtained for the lipid bilayer and Omp2a are ∼19 and 10.

Thermomechanical Response of a Representative Porin for Biomimetics.

The thermomechanical response of Omp2a, a representative porin used for the fabrication of smart biomimetic nanomembranes, has been characterized using microcantilever technology and compared with standard proteins. For this purpose, thermally induced transitions involving the conversion of stable trimers to bigger aggregates, local reorganizations based on the strengthening or weakening of intermolecular interactions, and protein denaturation have been detected by the microcantilever resonance frequency and deflection as a function of the temperature. Measurements have been carried out on arrays of 8-microcantilevers functionalized with proteins (Omp2a, lysozyme and bovine serum albumin).

Cell Responses to Electrical Pulse Stimulation for Anticancer Drug Release.

Electrical stimulation is an attractive approach to tune on-demand drug release in the body as it relies on simple setups and requires typically 1 V or less. Although many studies have been focused on the development of potential smart materials for electrically controlled drug release, as well as on the exploration of different delivery mechanisms, progress in the field is slow because the response of cells exposed to external electrical stimulus is frequently omitted from such investigations. In this work, we monitor the behavior of prostate and breast cancer cells (PC-3 and MCF7, respectively) exposed to electroactive platforms loaded with curcumin, a hydrophobic anticancer drug.

Drug delivery systems based on intrinsically conducting polymers.

This work provides an overview of the up to date research related to intrinsically conducting polymers (ICPs) and their function as novel drug delivery systems (DDSs). Drugs administrated to patients do not always reach the targeted organ, which may affect other tissues leading to undesired side-effects. To overcome these problems, DDSs are under development.

Biomimetic hybrid membranes: incorporation of transport proteins/peptides into polymer supports.

Molecular sensing, water purification and desalination, drug delivery, and DNA sequencing are some striking applications of biomimetic hybrid membranes. These devices take advantage of biomolecules, which have gained excellence in their specificity and efficiency during billions of years, and of artificial materials that load the purified biological molecules and provide technological properties, such as robustness, scalability, and suitable nanofeatures to confine the biomolecules. Recent methodological advances allow more precise control of polymer membranes that support the biomacromolecules, and are expected to improve the design of the next generation of membranes as well as their applicability.

Smart Drug Delivery from Electrospun Fibers through Electroresponsive Polymeric Nanoparticles.

Electrospun poly(ε-caprolactone) (PCL) microfibers loaded with poly(3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs) and curcumin with diameter of 3.9 ± 0.7 μm have been prepared and subsequently characterized using different spectroscopic techniques, scanning electron microscopy, and atomic force microscopy.

Electrostimulated Release of Neutral Drugs from Polythiophene Nanoparticles: Smart Regulation of Drug-Polymer Interactions.

Poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles are loaded with curcumin and piperine by in situ emulsion polymerization using dodecyl benzene sulfonic acid both as a stabilizer and a doping agent. The loaded drugs affect the morphology, size, and colloidal stability of the nanoparticles. Furthermore, kinetics studies of nonstimulated drug release have evidenced that polymer···drug interactions are stronger for curcumin than for piperine.

Weighing biointeractions between fibrin(ogen) and clot-binding peptides using microcantilever sensors.

Peptides homing tumor vasculature are considered promising molecular imaging agents for cancer detection at an early stage. In addition to their high binding affinity, improved tissue penetrating ability, and low immunogenicity, they can deliver targeted anticancer drugs, thus expanding therapeutic treatments. Among those, CREKA, a linear peptide that specifically binds to clotted-plasma proteins in tumor vessels, has been recently employed to design bioactive systems able to target different cancer types.

Confinement of a β-barrel protein in nanoperforated free-standing nanomembranes for ion transport.

Bioinspired free-standing nanomembranes (FSNMs) for selective ion transport have been tailored by immobilizing the Omp2a β-barrel membrane protein inside nanoperforations created in flexible poly(lactic acid) (PLA) nanomembranes. Perforated PLA FSNMs have been prepared by spin-coating a 99 : 1 PLA : poly(vinyl alcohol) mixture, and through a phase segregation process nanofeatures with dimensions similar to the entire nanomembrane thickness (∼110 nm) were induced. These nanofeatures have subsequently been transformed into nanoperforations (diameter: ∼51 nm) by selective solvent etching.