3D Biofabrication of a Cardiac Tissue Construct for Sustained Longevity and Function

Abstract

In this study, we developed three-dimensional (3D) printed annular ring-like scaffolds of hydrogel (gelatin–alginate) constructs encapsulated with a mixture of human cardiac AC16 cardiomyocytes (CMs), fibroblasts (CFs), and microvascular endothelial cells (ECs) as cardiac organoid models in preparation for investigating the role of microgravity in cardiovascular disease initiation and development. We studied the mechanical properties of the acellular scaffolds and confirmed their cell compatibility as well as heterocellular coupling for cardiac tissue engineering. Rheological analysis performed on the acellular scaffolds showed the scaffolds to be elastogenic with elastic modulus within the range of a native in vivo heart tissue. The microstructural and physicochemical properties of the scaffolds analyzed through scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy-attenuated total reflectance (ATR-FTIR) confirmed the mechanical and functional stability of the scaffolds for long-term use in in vitro cell culture studies. HL-1 cardiomyocytes bioprinted in these hydrogel scaffolds exhibited contractile functions over a sustained period of culture. Cell mixtures containing CMs, CFs, and ECs encapsulated within the 3D printed hydrogel scaffolds exhibited a significant increase in viability and proliferation over 21 days, as shown by flow cytometry analysis. Moreover, via the expression of specific cardiac biomarkers, cardiac-specific cell functionality was confirmed. Our study depicted the heterocellular cardiac cell interactions, which is extremely important for the maintenance of normal physiology of the cardiac wall in vivo and significantly increased over a period of 21 days in in vitro. This 3D bioprinted “cardiac organoid” model can be adopted to simulate cardiac environments in which cellular crosstalk in diseased pathologies like cardiac atrophy can be studied in vitro and can further be used for drug cytotoxicity screening or underlying disease mechanisms.

Insight into Heart-Tailored Architectures of Hydrogel to Restore Cardiac Functions after Myocardial Infarction

“…With the addition of gelatin to enhance the structural stability and mechanical strength of scaffolds, a 3D bioprinted cardiac tissue model by encapsulating cardiac cells within gelatin and alginate with high guluronic acid scaffolds was accompanied by highly interconnected pores to promote heterocellular coupling between cardiac fibroblasts and cardiac myocytes along with engaging the endothelial cells (ECs) via paracrine signaling …”

“…83 With the addition of gelatin to enhance the structural stability and mechanical strength of scaffolds, a 3D bioprinted cardiac tissue model by encapsulating cardiac cells within gelatin and alginate with high guluronic acid scaffolds was accompanied by highly interconnected pores to promote heterocellular coupling between cardiac fibroblasts and cardiac myocytes along with engaging the endothelial cells (ECs) via paracrine signaling. 84 Coordination bonds formed by some specific metal ions (e.g., Ca 2+ , Zn 2+ and Fe 3+ ) can be reversibly associated and dissociated, which in turn can improve the mechanical properties. 85 An integrated single "all-in-one" in situ dual cross-linking conductive hydrogel was constructed by mixing modified HA, gelatin and Fe 3+ , which provides mechanical and self-healing properties adapted to the cardiac systolic-diastolic cycle.…”

Challenges and considerations for single-cell and spatially resolved transcriptomics sample collection during spaceflight

“…A few examples of include Biopack, 130 SABL from BioServe Space Technologies (T. Niederwieser, 2015, 45th International Conference on Environmental Systems, conference), Kubik, 131 NanoRacks Frame-3, STaARS-1 EF 132 , and the CubeLab from Space Tango. 133 A more current system called the ScienceTaxi ( https://www.yurigravity.com/our-service ) developed by Yuri Gravity can be integrated into the ISS and into the newer stations coming online; an autonomous version of the ScienceTaxi is in development. This small sampling of hardware options is indicative of the demand for laboratory equipment that is operational in a weightless space environment and the importance of biological experiments conducted in space.…”

Hybrid biomanufacturing systems applied in tissue regeneration

“…AM enables the precise spatial deposition of biological materials, viable cells, and biochemicals to fabricate 3D biological structures[ 5 ]. AB technologies have found extensive applications in the biomedical area, including skin (for example, full-thickness skin substitutes or wound dressings)[ 6 ], orthopedic[ 7 ], dental[ 8 ], osteochondral[ 9 ], cardiovascular[ 10 ], and other soft-tissue engineering applications (e.g., pancreas and liver)[ 10 ]. However, the complexity of tissues and organs prohibits the use of a single technique due to limitations inherent to each AM technology (e.g., relatively low printing resolution and limited material applicability of specific technologies).…”