Publications

Bioelectrical cues are essential for cardiac function and regeneration, yet current electrostimulation strategies rely on invasive electrodes that limit spatial control and clinical translation. Here, we report magnetoelectric nanocomposite hydrogels that combine core-shell CoFe2O4@BiFeO3 magnetoelectric nanoparticles (ME NPs) with a photo-cross-linked methacrylated gelatin (GelMA) network, enabling wireless electroactivity through externally applied magnetic fields within a soft, biomimetic three-dimensional scaffold. Structural and physicochemical analyses confirmed the successful synthesis of crystalline core-shell ME NPs with strong interfacial coupling, as demonstrated by transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and magnetic hysteresis measurements showing exchange bias effects. Homogeneous incorporation of ME NPs within GelMA produced highly porous and interconnected hydrogels, as revealed by scanning electron microscopy and microcomputed tomography. The presence of nanoparticles reduced equilibrium swelling and refined pore architecture, suggesting increased effective cross-linking density and nanoparticle-polymer interactions. Mechanical testing showed soft elastomeric behavior with compressive moduli compatible with cardiac tissue. Under dynamic magnetic stimulation, magnetoelectric hydrogels significantly enhanced cardiac cell viability, proliferation, and morphological organization compared with pristine GelMA controls. After 10 days, the metabolic activity of cells cultured on GelMA-ME NP hydrogels under stimulation was approximately 3-fold higher than that of unstimulated GelMA. These results demonstrate that magnetoelectric hydrogels provide an effective platform for wireless electrostimulation, offering promising opportunities for cardiac tissue engineering and implantable bioelectronic therapies without wired electrodes.

JTD Keywords: Cardiac tissue engineering, Core-shell nanoparticles, Fields, Gelma hydrogels, Magnetoelectric nanocomposites, Tissue, Wireless electrostimulation

3D in vitro model systems, such as hydrogels, have garnered popularity due to their ability to more accurately recapitulate in vivo environments compared to 2D cell culture systems. However, methods which involve casting hydrogels by hand may be time consuming, have poor reproducibility, and reduced capacity to generate complex structures. Hence, 3D bioprinting has emerged as a useful tool for the high throughput production of in vitro tissue models such as hydrogels and complex constructs. Here, we demonstrate the mechanical properties, printability, and ability to support single cells and spheroids in culture for two highly characterised composite bioinks: Alginate/Gelatin (AlgGel), which is ionically crosslinked, and Alginate/Gelatin Methacrylate (GelMA) (AlgGelMA), whereby the GelMA is crosslinked by illumination with UV light. In this study, we engineered gels that exhibit a wide range of stiffnesses, which vary due to the concentration of crosslinking polymer present. AlgGel hydrogels were softer (1.5-4.5 kPa), and stiffness decreased with time in culture, however, AlgGelMA hydrogels were stiffer (6-40 kPa), and the stiffness increased with time. Microarchitectural studies using Scanning Electron Microscopy and Microcomputed Tomography (mu CT) revealed that hydrogels produced using both bioinks bore a highly porous structure, further simulating in vivo conditions. To assess the ability of both bioink families to support cell culture, the Acute Myeloid Leukaemia cell line THP-1 and human Mesenchymal Stem Cells (hMSCs) as single cells and spheroids were bioprinted in each bioink. Interestingly, THP-1 cells formed larger clusters when cultured within AlgGel bioinks compared to AlgGelMA. Additionally, hMSCs appeared to be unable to migrate through the AlgGel matrix, as single hMSCs displayed rounded morphologies and hMSC spheroid shape was not disrupted after seven days. Contrastingly, hMSCs and spheroids cultured within AlgGelMA hydrogels were able to invade the gel matrix and migrate. Together, these data demonstrate that both AlgGel and AlgGelMA bioinks show promise for use as the basis of 3D bioprinted in vitro tissue models.

JTD Keywords: Alginate, Bioprinting, Culture, Endothelial cell, Gelma, Hydrogels, Matrix, Mode, Morphology, Porosity, Spheroids, Stem cells, Stem-cells, Substrate stiffness, Tissues

The intestine is a complex tissue with a characteristic three-dimensional (3D) crypt-villus architecture, which plays a key role in the intestinal function. This function is also regulated by the intestinal stroma that actively supports the intestinal epithelium, maintaining the homeostasis of the tissue. Efforts to account for the 3D complex structure of the intestinal tissue have been focused mainly in mimicking the epithelial barrier, while solutions to include the stromal compartment are scarce and unpractical to be used in routine experiments. Here we demonstrate that by employing an optimized bioink formulation and the suitable printing parameters it is possible to produce fibroblast-laden crypt-villus structures by means of digital light projection stereolithography (DLP-SLA). This process provides excellent cell viability, accurate spatial resolution, and high printing throughput, resulting in a robust biofabrication approach that yields functional gut mucosa tissues compatible with conventional testing techniques.Copyright © 2023 Elsevier B.V. All rights reserved.

JTD Keywords: 3d microstructure, barrier, cells, epithelial-stromal interactions, gelma-pegda soft hydrogels, growth, hydrogel, intestinal mucosa model, methacrylamide, microfabrication, proliferation, scaffold, stereolithography, 3d bioprinting, 3d microstructure, Epithelial-stromal interactions, Fibroblasts, Gelma-pegda soft hydrogels, Intestinal mucosa model

JTD Keywords: 4-ethylenedioxythiophene), carbon nanoparticles, conductive hydrogel, manganese oxide poly(3, sensors, supercapacitor, supercapacitors, temperature sensor, Alginate, Carbon nanotubes

Musculoskeletal disorders are a significant burden on the global economy and public health. Hydrogels have significant potential for enhancing the repair of damaged and injured musculoskeletal tissues as cell or drug delivery systems. Hydrogels have unique physicochemical properties which make them promising platforms for controlling cell functions. Gelatin methacryloyl (GelMA) hydrogel in particular has been extensively investigated as a promising biomaterial due to its tuneable and beneficial properties and has been widely used in different biomedical applications. In this review, a detailed overview of GelMA synthesis, hydrogel design and applications in regenerative medicine is provided. After summarising recent progress in hydrogels more broadly, we highlight recent advances of GelMA hydrogels in the emerging fields of musculoskeletal drug delivery, involving therapeutic drugs (e.g., growth factors, antimicrobial molecules, immunomodulatory drugs and cells), delivery approaches (e.g., single-, dual-release system), and material design (e.g., addition of organic or inorganic materials, 3D printing). The review concludes with future perspectives and associated challenges for developing local drug delivery for musculoskeletal applications.

JTD Keywords: drug delivery, gelatin, gelma, hydrogel, Drug delivery, Gelatin, Gelma, Hydrogel, Musculoskeletal tissue

In this paper, we fabricate a flexible and location traceable micromotor, called organo-motor, assisted by microfluidic devices and with high throughput. The organo-motors are composed of organic hydrogel material, poly (ethylene glycol) diacrylate (PEGDA), which can provide the flexibility of their structure. For spatial and temporal traceability of the organo-motors under magnetic resonance imaging (MRI), superparamagnetic iron oxide nanoparticles (SPION; Fe3O4) were incorporated into the PEGDA microhydrogels. Furthermore, a thin layer of platinum (Pt) was deposited onto one side of the SPION-PEGDA microhydrogels providing geometrical asymmetry and catalytic propulsion in aqueous fluids containing hydrogen peroxide solution, H2O2. Furthermore, the motion of the organo-motor was controlled by a small external magnet enabled by the presence of SPION in the motor architecture.

JTD Keywords: Flexible, Hydrogel, Magnetic resonance imaging, Microfluidics, Micromotor, Microparticle, Organo-motor, Poly (ethylene glycol) diacrylate, Self-propulsion, Superparamagnetic iron oxide nanoparticles