There is a need for developing a living tissue-engineered whole heart for transplantation. One solution is to create acellular myocardial tissue scaffolds and seed them with autologous cells for full reconstitution. Our goal was to reconstitute the endocardial layer of both ventricular cavities and the septum surfaces of decellularized hearts. Whole rabbit hearts were decellularized using a biventricular perfusion system. We designed a rotational support system for the scaffolds and seeded the two cardiac cavities with human fibroblasts, collagen hydrogels, fibrin hydrogel, and human endothelial cells in a layer-by-layer fashion. Afterwards, the scaffold was subjected to in vitro conditioning in a purpose-designed bioreactor. Results showed that hydrogels infused onto most surfaces and pores of the scaffold. Seeded cells effectively adhered to many areas of the two ventricles while remaining active by secreting new matrix proteins. These results indicate that layer-by-layer deposition can aid in the reconstitution of the cardiac endocardium.
There is a need for developing a living whole heart for transplantation. In this study, we developed a perfusion system to remove all cells from rabbit hearts, while leaving the connective tissue collagen fibers intact. We then developed a rotational bioreactor system to seed the hearts with human cells in a layer-by-layer fashion by suspending human fibroblasts and endothelial cells in fibrin and collagen gels as carriers. Using these systems, we successfully reconstituted an important internal layer of the heart, the endocardium, lining the cavities of the heart, with most cells remaining alive and active.
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Acrylonitrile butadiene styrene
Sodium dodecyl sulfate ethanol
Human adipose-derived stem cell
Human aortic endothelial cell
Dulbecco’s modified eagle medium
Fetal bovine serum
Revolutions per minute
Scanning electron microscopy
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The authors wish to thank Godly-Snell Research Center for providing rabbit hearts used in preliminary studies pertaining to this data. They would also like to acknowledge Advanced Materials and Research Laboratory for providing training and access to their scanning electron microscopes.
Sources of Funding
This project was funded by the Harriet and Jerry Dempsey Bioengineering Professorship Award (to D.S.).
Conflict of Interest
The authors declare that they have no competing interests.
Human Subjects/Informed Consent Statement
No human studies were carried out by the authors for this article.
No animal studies were carried out by the authors for this article.
Future studies will be geared towards improvements in seeding efficacy, long-term conditioning in the bioreactor, and assessment of biological functionality of the newly reconstituted endocardium. Using this system, we will also perfuse endothelial cells through the scaffold to reconstitute the coronary vasculature.
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Compton, C., Canavan, J., Mcleod, J. et al. Reconstitution of the Ventricular Endocardium Within Acellular Hearts. Regen. Eng. Transl. Med. 6, 90–100 (2020). https://doi.org/10.1007/s40883-019-00099-1
- Stem cells
- Tissue engineering
- Acellular cardiac scaffolds