Mid-term function and remodeling potential of tissue engineered tricuspid valve: Histology and biomechanics

Abstract

ObjectiveTricuspid valve reconstruction using a small intestinal submucosal porcine extracellular matrix (ECM) tube graft is hypothesized to be durable for six months and show signs of recellularization and growth potential. The purpose was to histologically and biomechanically test ECM valves before and after six months of implantation in pigs for comparison with native valves. MethodsTen 60 kg pigs were included, which survived tricuspid valve tube graft insertion. Anterior and septal tricuspid leaflets were explanted from all animals surviving more than one month and examined histologically (n = 9). Endothelialization, collagen content, mineralization, neovascularization, burst strength and tensile strength were determined for native valves (n = 5), ECM before implantation (n = 5), and ECM after six months (n = 5). ResultsCollagen density was significantly larger in ECM at implantation (baseline) compared to native leaflet tissue (0.3 ± 0.02 mg/mm3 vs. 0.1 ± 0.03 mg/mm3, p < .0001), but collagen density decreased and reached native leaflet collagen content, six months after ECM implantation (native vs. ECM valve at six months: 0.1 ± 0.03 mg/mm3 vs. 0.2 ± 0.05 mg/mm3, p = .8).Histologically, ECM valves showed endothelialization, host cell infiltration and structural collagen organization together with elastin generation after six months, indicating tissue remodeling and -engineering together with gradual development of a close-to-native leaflet structure without foreign body response. ConclusionsECM tricuspid tube grafts were stronger than native leaflet tissue. Histologically, the acellular ECM tube grafts showed evidence of constructive tissue remodeling with endothelialization and connective tissue organization. These findings support the concept of tissue engineering and recellularization, which are prerequisites for growth.