Figure 8

Summary of host cell infiltration behavior in response to the geometries of first- and second-generation TEM-based TEHVs. (A) We hypothesize that first-generation TEHVs presented a non-physiological geometry, which hindered the physiological formation of blood vortexes (arrows), thereby favoring the deposition of erythrocytes and leukocytes in the hinge region shortly after implantation. At 8 weeks follow-up, first-generation TEHVs showed sustained short-term performance with high expression of M1 macrophages and α-SMA⁺ cells markers. These inflammatory cells were mostly localized in the implanted TEM material, while few to no cells were detected in the newly formed pannus at the hinge area. Endothelialization was incomplete at this stage. After 24 weeks follow-up, first-generation TEHVs exhibited moderate to severe insufficiency, with a chronic inflammation and extensive maladaptive remodeling of the TEM material and pannus. This maladaptive remodeling was associated with evident hinge region thickening, abundant M1 and M2 macrophages, and α-SMA⁺ cells expression. Image was created using the software Tinkercad under Creative Commons license Non-Commercial 3.0 and Servier Medical Art under Creative Commons license 3.0. (B) Second-generation TEHVs presented a computational modeling-inspired geometry, which allowed a more physiological performance of the TEHVs after implantation, thereby possibly favoring vortex formation and blood wash-out from the hinge area. After 8 weeks, second-generation TEHVs displayed sustained performance, with few M1 macrophages and negligible presence of M2 and α-SMA⁺ cells in the hinge region. At this timepoint, endothelialization of the valve surfaces, and in particular, of the hinge area was complete. At 52 weeks, second-generation TEHVs still exhibited excellent performance, with a similar cellular composition to the 8 weeks timepoint, comprising M1 macrophages and negligible presence of M2 and α-SMA⁺ cells. This inflammatory response highlighted the resolution and adaptive positive remodeling by the host towards second-generation TEM-based TEHVs. Image was created using the software Tinkercad under Creative Commons license Non-Commercial 3.0 and Servier Medical Art under Creative Commons license 3.0.