oa Decellularized Tissue Engineered Heart Valves: Infiltration, Inflammation and Regeneration?

Decellularized native biological tissue is currently investigated for its use as heart valve tissue engineering scaffold. Important features are the intact native matrix structure and retained mechanical properties. Unfortunately, these materials lack sufficient cell infiltration, reducing its remodeling potential. As shown in our recent ovine study (see abstract A. Driessen-Mol), in vitro cultured decellularized tissue-engineered heart valves facilitate complete cell infiltration, even after only 5 hours in vivo. This rapid cell infiltration is essential for remodeling. In general, all implanted biological materials evoke an inflammatory response, resulting in undesired chronic inflammation and/or fibrosis or in desired regeneration. Macrophage phenotype (M1/M2) is demonstrated to play an essential role in regulating the delicate balance between inflammation and regeneration. More in-depth insights underlying the process of cell infiltration and subsequent host inflammation response is crucial to achieve regeneration and is studied here using an in vitro model system. For this in vitro study, we used an adapted setup of the IBIDI flow chamber system and simulated native pulmonary conditions. A mix of mono- and polynuclear cells was isolated from fresh ovine blood and added to the IBIDI system to circulate along inserted pieces of tissues. Ovine tissue-engineered patches were cultured according to our protocols for heart valve tissue engineering. In short, ovine vascular cells were isolated and cultured for 4 weeks on a PGA-P4HB scaffold. The patches were decellularized afterwards. Cell infiltration into both decellularized ovine tissue-engineered patches and decellularized native ovine pulmonary leaflets was studied up to 5 hours. Thereafter, the tissues were fixed, stained with DAPI and visualized by confocal microscopy. Tremendous cell infiltration was observed at the edges in the decellularized tissue-engineered patches, whereas no clear cell infiltration was observed for the decellularized native leaflets. These first preliminary in vitro results are indicative of the host body’s capacity to rapidly infiltrate decellularized tissue-engineered matrices with inflammation-associated blood cells. Further research for cell type identification and tissue regenerative capacity is ongoing. The European Union’s Seventh Framework Program is acknowledged for funding this study.