Speaker
Description
Introduction
Cardiovascular diseases (CVDs) are the leading cause of death globally, accounting for approximately 1.6 million deaths annually [1]. Among them, myocardial infarction (MI) is particularly concerning due to its high incidence, mortality, and adverse prognosis. These challenges are amplified in ageing populations, making MI a growing public health issue. Current treatment approaches including pharmacological therapies and surgical interventions can lighten symptoms but do not regenerate damaged myocardium. Heart transplantation remains the only curative option for end-stage cases but is constrained by donor shortages and immune rejection risks. These challenges underscore the pressing need for advance therapeutic strategies to repair and regenerate cardiac tissue.
Cardiac patches (CP) are engineered tissues designed to replace damaged myocardium, thus offering promising alternative to transplantation [2-4]. Therefore, in this study, we developed a hybrid hydrogel composed of gelatin methacrylate (GELMA) and carboxymethyl cellulose methacrylate (CMCMA), tailored to match the mechanical properties of the native ECM. To achieve this, we optimized various parameters including the concentrations of GELMA-CMCMA, crosslinker concentration, and UV exposure time. The resulting bioink was formulated by encapsulating AC16 human cardiomyocyte cells within the CMCMA-GELMA hydrogel. The cytocompatibility of the bioink was subsequently evaluated to ensure a supportive environment for cell viability and function.
Materials and Methods
GELMA and CMCMA were synthesized via methacrylation and characterized using Fourier-transform infrared spectroscopy and nuclear magnetic resonance. Hydrogels were prepared at varying GELMA-CMCMA ratios and crosslinked using a dual enzymatic and photo-crosslinking. Rheological properties, including shear-thinning behavior and viscoelasticity, were analyzed using oscillatory rheometer. Mechanical properties such as stiffness, Young’s modulus, and tensile strength were measured through uniaxial compression and tensile tests. Bioprinting parameters such as nozzle diameter, extrusion pressure, print speed, and UV exposure time were optimized to achieve high-resolution, structurally stable constructs. Printability was assessed by evaluating filament formation, shape fidelity, printability index and layer-stacking efficiency (Figure 1). Hydrogel stability post-printing was examined by monitoring swelling, degradation, and gelatin release over time. Further mechanical characterization was conducted using atomic force microscopy to ensure the hydrogels could withstand dynamic cardiac conditions. AC16 human cardiomyocytes were encapsulated within the hydrogels and the developed bioinks were used to assess biocompatibility. Cell viability was analyzed using live/dead staining, and functional performance was evaluated over extended culture periods (Figure 2 A-B).
Results
NMR confirmed successful methacrylation of both GELMA and CMCMA. The hybrid hydrogels exhibited optimal shear-thinning behavior, suitable for extrusion bioprinting. High print fidelity and minimal deformation were observed post-printing. The dual crosslinked hydrogels maintained mechanical stability over time with controlled swelling and degradation. Encapsulated AC16 cells demonstrated high viability, indicating good cytocompatibility. The printed TECPs supported cell attachment, proliferation, and metabolic activity. Future work will evaluate the patches’ ability to support CM contractility.
References
(1) Martin, S. S. et al, 2025, 10.1161/CIR.0000000000001209
(2) Jacot, J. G. et al., 2009, 10.1016/J.JBIOMECH.2009.09.014
(3) Miller and Penta, 2023, 10.1007/s10237-023-01698-2
(4) Nordsletten, D. et al., 2021, 10.1016/j.actbio.2021.08.036
Acknowledgements: Sonata (2022/47/D/ST8/03467) and First Team FENG (FENG.02.02-IP.05-0045/23).
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