Portable bioreactor for perfusion and electrical stimulation of engineered cardiac tissue

Cardiac tissue engineering aims to create functional tissue constructs that can reestablish the structure and function of injured myocardium. Although bioreactors have facilitated the engineering of cardiac patches of clinically relevant size in vitro, a major drawback remains the transportation of the engineered tissues from a production facility to a medical operation facility while maintaining tissue viability and preventing contamination. Furthermore, after implantation, most of the cells are endangered by hypoxic conditions that exist before vascular flow is established. We developed a portable device that provides the perfusion and electrical stimulation necessary to engineer cardiac tissue in vitro, and to transport it to the site where it will be implantated. The micropump-powered perfusion apparatus may additionally function as an extracorporeal active pumping system providing nutrients and oxygen supply to the graft post-implantation. Such a system, through perfusion of oxygenated media and bioactive molecules (e.g. growth factors), could transiently support the tissue construct until it connects to the host vasculature and heart muscle, after which it could be taken away or let biodegrade.

[1]  André Colas,et al.  Silicone Biomaterials : History and Chemistry & Medical Applications of Silicones , 2004 .

[2]  Jianwen Luo,et al.  Biomimetic perfusion and electrical stimulation applied in concert improved the assembly of engineered cardiac tissue , 2012, Journal of tissue engineering and regenerative medicine.

[3]  Gordana Vunjak-Novakovic,et al.  Perfusion seeding of channeled elastomeric scaffolds with myocytes and endothelial cells for cardiac tissue engineering , 2010, Biotechnology progress.

[4]  Andreas Hess,et al.  Cardiac Grafting of Engineered Heart Tissue in Syngenic Rats , 2002, Circulation.

[5]  Milica Radisic,et al.  Electrical stimulation systems for cardiac tissue engineering , 2009, Nature Protocols.

[6]  Gordana Vunjak-Novakovic,et al.  Bioengineering heart muscle: a paradigm for regenerative medicine. , 2011, Annual review of biomedical engineering.

[7]  N. Tandon,et al.  Optimization of electrical stimulation parameters for cardiac tissue engineering , 2011, Journal of tissue engineering and regenerative medicine.

[8]  Andreas Hess,et al.  Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts , 2006, Nature Medicine.

[9]  Narine Sarvazyan,et al.  Feasibility of Long-Distance Transfer for High Resolution Optical Mapping of Cardiac Tissue Constructs , 2012 .

[10]  Hillel Laks,et al.  Analysis of oxygen transport in a diffusion‐limited model of engineered heart tissue , 2007, Biotechnology and bioengineering.

[11]  C. Cannizzaro,et al.  Microfluidic device generating stable concentration gradients for long term cell culture: application to Wnt3a regulation of β-catenin signaling. , 2010, Lab on a chip.

[12]  Milica Radisic,et al.  Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Masayuki Yamato,et al.  Polysurgery of cell sheet grafts overcomes diffusion limits to produce thick, vascularized myocardial tissues , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[14]  Milica Radisic,et al.  Medium perfusion enables engineering of compact and contractile cardiac tissue. , 2004, American journal of physiology. Heart and circulatory physiology.

[15]  Milica Radisic,et al.  Cardiac tissue engineering using perfusion bioreactor systems , 2008, Nature Protocols.