Inflammatory and regenerative processes in bioresorbable synthetic pulmonary valves up to two years in sheep–Spatiotemporal insights augmented by Raman microspectroscopy

In situ heart valve tissue engineering is an emerging approach in which resorbable, off-the-shelf available scaffolds are used to induce endogenous restoration. Such designed recruit cells vivo , subsequently resorb polymer and produce remodel new valvular . Recently, preclinical studies using electrospun supramolecular elastomeric grafts have shown that this enables regeneration of pulmonary valves with long-term functionality However, the evolution mechanisms inflammation, absorption largely unknown, adverse remodeling intra- inter-valvular variability been reported. Therefore, goal present study was gain a mechanistic understanding regenerative processes by combining routine histology immunohistochemistry, comprehensive sheep-specific antibody panel, Raman microspectroscopy for spatiotemporal analysis tissue-engineered follow-up 24 months from previous sheep. The analyses revealed strong spatial heterogeneity influx inflammatory cells, graft resorption, foreign body giant cells. Collagen maturation occurred predominantly between 6 12 after implantation, accompanied progressive switch more quiescent phenotype infiltrating properties interstitial Variability among specimens extent observed times months. Taken together, these findings advance key events material-driven engineering. This describes first time underly resorbable synthetic scaffolds. Using unique combinatorial immunohistochemistry microspectroscopy, important resorption formation pinpointed valves, up correlated heterogenous regional cellular repopulation, most likely instigated region-specific differences surrounding hemodynamics. research contribute synthetics, necessary enable rational design improved grafts, ensure safe robust clinical translation.