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

In vitro surrogate models of human cardiac tissue hold great promise in disease modeling, cardiotoxicity testing, and future applications in regenerative medicine. However, the generation of engineered human cardiac constructs with tissue-like functionality is currently thwarted by difficulties in achieving efficient maturation at the cellular and/or tissular level. Here, we report on the design and implementation of a platform for the production of engineered cardiac macrotissues from human pluripotent stem cells (PSCs), which we term “CardioSlice.” PSC-derived cardiomyocytes, together with human fibroblasts, are seeded into large 3D porous scaffolds and cultured using a parallelized perfusion bioreactor with custom-made culture chambers. Continuous electrical stimulation for 2 weeks promotes cardiomyocyte alignment and synchronization, and the emergence of cardiac tissue-like properties. These include electrocardiogram-like signals that can be readily measured on the surface of CardioSlice constructs, and a response to proarrhythmic drugs that is predictive of their effect in human patients.

JTD Keywords: Cardiac tissue engineering, CardioSlice, ECG-like signals, Electrical stimulation, Heart physiology, Human induced pluripotent stem cells, Perfusion bioreactor, Tissue-like properties