Tissue Engineering of heart valves—Immunologic and inflammatory challenges of the allograft scaffold

Abstract 

Tissue Engineering of heart valves is aimed to produce valve substitutes which are accepted by the recipient indistinguishable of his own valve, function physiologically from the day of the implantation, perform reliably during the early remodeling period and long term and importantly to have growth potential in children.

However, many challenges have to be overcome to realize this goal. Some of these relate to design, defining the ideal scaffold for such a heart valve and the ideal cell source and method of repopulation of the scaffold with cells. The focus of this review is the challenges posed by the immunologic and inflammatory responses of the host against tissue engineered heart valves, specifically of decellularized xenogeneic and allogeneic tissues.

Decellularization is being used as the method of choice to reduce or eliminate the cellular components of both xenogeneinc and allogeneic tissues. It has been documented that completeness of decellularization is important and the various protocols described in the literature differ importantly. In incompletely decellularized porcine tissue the xenoantigen Gal (alpha 1,3) Gal is detected which may be responsible for an immediate hyperacute rejection type host response. Thrombocyte activation and inflammation are closely interrelated. Thrombocyte adherence and activation in both human and porcine decellularized tissue was observed and was prevented by reseeding with endothelial cells. Decellularization was furthermore documented to reduce the early non-specific inflammatory response more in human tissues than in porcine tissues. The specific humoral host response against decellularized allografts has been documented clinically.

We conclude that complete decellularization is suitable to reduce the specific host response against human tissue. The early inflammatory stimulus is also more effectively reduced in human tissue. Ex vivo repopulation of the scaffold appears necessary to avoid thrombocyte activation after implantation which may induce, perpetuate and increase early inflammation.

Keywords: Tissue engineering, Heart valve, Decellularization