Although progress has been made, a fully functional and transplantable cardiac patch is elusive due to several challenges. These challenges emanate from a nonoptimal understanding of different fields and expertise in biomedical, material, tissue, medicine, chemistry, biology, and mechanical engineering. Therefore, herein, an integrated approach for scaffold design requirements is critically reviewed. The scaffold manufacturing methods and prospects of electrical and mechanical stimulation to promote the maturation and function of cardiac tissues are presented. The mechanical behavior of cardiac cells and tissue functions are a fundamental requirement for a functional patch. Methods, data analysis, and mathematic models for measuring and quantifying cellular and tissue mechanics are discussed. Overall, this article serves as an overview, indicating the need for an “integrated” and collaborative approach to designing and fabricating functional and implantable cardiac tissues.
Electrical pacing/stimulations (EP) have been widely adopted to promote the maturation of hiPSC‐derived cardiomyocytes. However, there is a debate about their functions and effectiveness due to non‐optimized pacing conditions. Here, the effectiveness of EP (13 V cm−1, 2 ms in width, and 5 Hz frequency) on cardiac tissue beating mechanics are analyzed using digital image correlation (DIC). The cardiac tissues with and without EP at tissue culture time from day 2 to 11 (D2–D11) are characterized and compared. The results indicate EP decreased cardiac beating motion for ≈2–15 times, promote synchronization, and improve ion handling. A positive correlation between cardiac beating mechanics and ion handling is observed. DIC method can optimize chemical, mechanical, and electrical stimulation, which could help create more mature cardiac tissues.
more » « less- Award ID(s):
- 1647837
- NSF-PAR ID:
- 10362267
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Materials Technologies
- Volume:
- 6
- Issue:
- 12
- ISSN:
- 2365-709X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Bioprinting has emerged as an advanced method for fabricating complex 3D tissues. Despite the tremendous potential of 3D bioprinting, there are several drawbacks of current bioinks and printing methodologies that limit the ability to print elastic and highly vascularized tissues. In particular, fabrication of complex biomimetic structure that are entirely based on 3D bioprinting is still challenging primarily due to the lack of suitable bioinks with high printability, biocompatibility, biomimicry, and proper mechanical properties. To address these shortcomings, in this work the use of recombinant human tropoelastin as a highly biocompatible and elastic bioink for 3D printing of complex soft tissues is demonstrated. As proof of the concept, vascularized cardiac constructs are bioprinted and their functions are assessed in vitro and in vivo. The printed constructs demonstrate endothelium barrier function and spontaneous beating of cardiac muscle cells, which are important functions of cardiac tissue in vivo. Furthermore, the printed construct elicits minimal inflammatory responses, and is shown to be efficiently biodegraded in vivo when implanted subcutaneously in rats. Taken together, these results demonstrate the potential of the elastic bioink for printing 3D functional cardiac tissues, which can eventually be used for cardiac tissue replacement.
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Abstract Background and Aims Fibrotic tissue formed after myocardial infarction (MI) can be as detrimental as MI itself. However, current in vitro cardiac fibrosis models fail to recapitulate the complexities of post‐MI tissue. Moreover, although MI and subsequent fibrosis is most prominent in the aged population, the field suffers from inadequate aged tissue models. Herein, an aged human post‐MI tissue model, representing the native microenvironment weeks after initial infarction, is engineered using three‐dimensional bioprinting via creation of individual bioinks to specifically mimic three distinct regions: remote, border, and scar.
Methods The aged post‐MI tissue model is engineered through combination of gelatin methacryloyl, methacrylated hyaluronic acid, aged type I collagen, and photoinitiator at variable concentrations with different cell types, including aged human induced pluripotent stem cell‐derived cardiomyocytes, endothelial cells, cardiac fibroblasts, and cardiac myofibroblasts, by introducing a methodology which utilizes three printheads of the bioprinter to model aged myocardium. Then, using cell‐specific proteins, the cell types that comprised each region are confirmed using immunofluorescence. Next, the beating characteristics are analyzed. Finally, the engineered aged post‐MI tissue model is used as a benchtop platform to assess the therapeutic effects of stem cell‐derived extracellular vesicles on the scar region.
Results As a result, high viability (>74%) was observed in each region of the printed model. Constructs demonstrated functional behavior, exhibiting a beating velocity of 6.7 μm/s and a frequency of 0.3 Hz. Finally, the effectiveness of hiPSC‐EV and MSC‐EV treatment was assessed. While hiPSC‐EV treatment showed no significant changes, MSC‐EV treatment notably increased cardiomyocyte beating velocity, frequency, and confluency, suggesting a regenerative potential.
Conclusion In conclusion, we envision that our approach of modeling post‐MI aged myocardium utilizing three printheads of the bioprinter may be utilized for various applications in aged cardiac microenvironment modeling and testing novel therapeutics.
