Three-Dimensional Bio-Printed Cardiac Patch for Sustained Delivery of Extracellular Vesicles from the Interface

• Published in: Gels Vol. 8; no. 12; p. 769
• Main Authors: Bar, Assaf, Kryukov, Olga, Cohen, Smadar
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.11.2022; MDPI
• Subjects: 3D bioprinting; alginate sulfate; Alginates; Bioengineering; Biomedical materials; Cardiac arrhythmia; cardiac patch; Design; Drug delivery systems; Extracellular vesicles; Growth factors; Heart; Heparan sulfate; Heparin; Hydrogels; Mechanical properties; Modulus of elasticity; Phase transitions; Rheological properties; Signal transduction; Stiffness; Sulfates; Three dimensional printing; Tissue engineering; Transdermal medication; Transplantation; Transplants & implants; Viscosity; Israel; California; cardiac patch; alginate sulfate; 3D bioprinting; extracellular vesicles
• ISSN: 2310-2861; 2310-2861
• DOI: 10.3390/gels8120769

Cardiac tissue engineering has emerged as a promising strategy to treat infarcted cardiac tissues by replacing the injured region with an ex vivo fabricated functional cardiac patch. Nevertheless, integration of the transplanted patch with the host tissue is still a burden, limiting its clinical application. Here, a bi-functional, 3D bio-printed cardiac patch (CP) design is proposed, composed of a cell-laden compartment at its core and an extracellular vesicle (EV)-laden compartment at its shell for better integration of the CP with the host tissue. Alginate-based bioink solutions were developed for each compartment and characterized rheologically, examined for printability and their effect on residing cells or EVs. The resulting 3D bio-printed CP was examined for its mechanical stiffness, showing an elastic modulus between 4-5 kPa at day 1 post-printing, suitable for transplantation. Affinity binding of EVs to alginate sulfate (AlgS) was validated, exhibiting dissociation constant values similar to those of EVs with heparin. The incorporation of AlgS-EVs complexes within the shell bioink sustained EV release from the CP, with 88% cumulative release compared with 92% without AlgS by day 4. AlgS also prolonged the release profile by an additional 2 days, lasting 11 days overall. This CP design comprises great potential at promoting more efficient patch assimilation with the host.