Publications

Thanks to their biocompatibility and ability to support cell growth, alginate hydrogels are promising scaffolds for skin tissue regeneration. If conductive, they can further improve the wound healing process by electrical stimulation (ES). Herein, we explore the preparation and application of robust hydrogels synthesized via the thiol-yne click reaction, a highly efficient and rapid process. Hydrogels were obtained by functionalizing alginate with thiol groups and crosslinking them with a modified 3-arm polyethylene glycol (PEG) precursor (click-Alg). As a final step, the in situ chemical oxidative polymerization of poly(hydroxymethyl-3,4-ethylenedioxythiophene) (semi-interpenetrated PHMeEDOT) rendered them electro-responsive (click-Alg/PHMeEDOT). The gelation of the click-Alg hydrogels proceeded quickly (within 3 min), enabling rapid network formation for injectable application and resulting in high gel fraction, which ensured structural stability. After incorporating PHMeEDOT, a decrease in the pore size happened, while porosity remained predominantly open, with PHMeEDOT completely covering the pores surface. This coating enhanced the electrochemical response of click-Alg/PHMeEDOT hydrogels, whereas their mechanical similarity (with values of Young's modulus = 116 +/- 10.7 kPa) to skin tissue is expected to reduce mismatch risks, improve integration, and minimize stress-related healing issues. Optimized in vitro assays with Vero and HFF-1 cells subjected to 0.6 V for 20 min showed significant wound closure after 2 h, implying that increased electrochemical activity played a key role in promoting wound closure under ES. Overall, we highlight the synergy between both matrices and the effectiveness and potential of click-Alg/PHMeEDOT hydrogels as electrode-like wound dressings for electrically-driven skin tissue repair.

JTD Keywords: Alginate, Behavior, Cell, Collagen, Conducting polymer, Conductivity, Electrical stimulation, Fabrication, Hyaluronic-acid hydrogel, Hydrogel, In-vivo, Membranes, Model, Network, Thiol-yne click chemistry, Wound dressing

Medical devices such as vascular grafts, stents, and catheters are crucial for patient treatment but often suffer suboptimal integration with host tissues due to the nature of their surfaces. The materials commonly used, including metals and synthetic polymers, frequently lead to undesired immune responses and device failure. In this context, coating their surfaces with designer proteins has arisen as a promising strategy to improve the device's biointegration. Here, we present a bioinspired method for coating biomaterial surfaces with protein-engineered polymers designed to mimic tailored functions from the native extracellular matrix (ECM). Combining mussel-inspired catechol chemistry with bioorthogonal click chemistry, we developed a modular grafting method for the surface functionalization of metallic and polymeric implants using a bifunctional peptide containing azide and DOPA (3,4-dihydroxyphenylalanine) groups. This simple dip-coating process enabled the fabrication of bioactive elastin-like coatings with precise peptide presentation. The results reveal enhanced bioactivity and cytocompatibility, as evidenced by improved endothelial cell adhesion, proliferation, and heparin-binding capacity on coated surfaces. The versatility and effectiveness of this bioorthogonal coating method suggest significant potential for creating implant surfaces tailored to diverse clinical applications.

JTD Keywords: Adhesion, Binding, Biofunctional coatings, Cell response, Click chemistry, Coatings, Dopa, Elastin-like recombinamers, Fibronectin, Peptides, Polymers, Protein adsorption, Surface functionalization, Surfaces, Titanium

Herein, we describe the design and synthesis of a new variety of bio-based hydrogel films using a Cu(i)-catalyzed photo-click reaction. These films exhibited thermal-triggered swelling-deswelling and were constructed by crosslinking a triazide derivative of glycerol ethoxylate and dialkyne structures derived from isosorbide, a well-known plant-based platform molecule. The success of the click reaction was corroborated through infrared spectroscopy (FTIR) and the smooth surface of the obtained films was confirmed by scanning electron microscopy (SEM). The thermal characterization was carried out in terms of thermogravimetry (TGA) and differential scanning calorimetry (DSC), from which the decomposition onset and glass transition temperatures were determined, respectively. Additionally, mechanical properties of the samples were estimated by stress-strain experiments. Then, their swelling and deswelling properties were systematically examined in PBS buffer, revealing a thermoresponsive behavior that was successfully tested in the release of the anticancer drug doxorubicin. We also confirmed the non-cytotoxicity of these materials, which is a fundamental aspect for their potential use as drug carriers or tissue engineering matrices.

JTD Keywords: Biology, Click chemistry, Growth, Release

© The Royal Society of Chemistry 2021. A novel and versatile toolkit approach for the functionalization of biomaterials of different nature is described. This methodology is based on the solid-phase conjugation of specific anchoring units onto a resin-bound azido-functionalized peptide by using click chemistry. A synergistic multifunctional peptidic scaffold with cell adhesive properties was used as a model compound to showcase the versatility of this new approach. Titanium, gold and polylactic acid surfaces were biofunctionalized by this method, as validated by physicochemical surface characterization with XPS.In vitroassays using mesenchymal stem cells showed enhanced cell adhesion on the functionalized samples, proving the capacity of this strategy to efficiently bioactivate different types of biomaterials.

JTD Keywords: Biocompatible materials, Click chemistry, Peptides, Protein conformation

Here we describe a label-free electrochemical DNA sensor based on poly(3,4-ethylenedioxythiophene)-modified (PEDOT-modified) electrodes. An acetylene-terminated DNA probe, complementary to a specific "Hepatitis C" virus sequence, was immobilized onto azido-derivatized conducting PEDOT electrodes using "click" chemistry. DNA hybridization was then detected by differential pulse voltammetry, evaluating the changes in the electrochemical properties of the polymer produced by the recognition event. A limit of detection of 0.13. nM was achieved using this highly selective PEDOT-based genosensor, without the need for labeling techniques or microelectrode fabrication processes. These results are promising for the development of label-free and reagentless DNA hybridization sensors based on conducting polymeric substrates. Biosensors can be easily prepared using any DNA sequence containing an alkyne moiety. The data presented here reveal the potential of this DNA sensor for diagnostic applications in the screening of diseases, such as "Hepatitis C", and genetic mutations.

JTD Keywords: Azido-EDOT, Click chemistry, Differential pulse voltammetry, DNA biosensor, Electrochemistry, Hepatitis C virus

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JTD Keywords: Biotin, Click chemistry, Dip-pen nanolithography, Oligonucleotides, Surfaces