Mechanical and finite element evaluation of a bioprinted scaffold following recellularization in a rat subcutaneous model

Tissue engineered heart valves (TEHV) provide several advantages over currently available aortic heart valve replacements. Bioprinting provides a patient-specific means of developing a TEHV scaffold from imaging data, and the capability to embed the patient's own cells within the scaffold. In this work we investigated the remodeling capacity of a collagen-based bio-ink by implanting bioprinted disks in a rat subcutaneous model for 2, 4 and 12 weeks and evaluating the mechanical response using biaxial testing and subsequent finite element (FE) modeling. Samples explanted after 2 and 4 weeks showed inferior mechanical properties compared to native tissues while 12 week explants showed a mechanical response of similar magnitude but did not demonstrate the anisotropy present in native tissues. In the FE analysis, the model utilizing mechanical properties from samples explanted after 12 weeks showed the closest mechanical behavior to the native tissues. However, in diastole native tissues showed higher stress in the leaflet belly and lower strain at the commissures compared to 12 week explants, likely due to the anisotropy present in the native tissues. Thus, either further remodeling is required in situ in the aortic valve position or by in vitro preconditioning in an environment such as a bioreactor. Regardless, these results demonstrate the utility of FE analysis to optimize bioprinting process parameters for the most favorable in vivo mechanical performance.