Biointegration and Growth of Porcine Valved Pulmonary Conduits in a Sheep Model

Abstract

As there is currently no suitable valved pulmonary conduit for small children, porcine conduits treated by the L-Hydro process were implanted into 9 newborn lambs to investigate growth potential. Of the 8 survivors, 7 were kept alive for 12 months after implantation. The diameter of the conduit and gradient across the valve were evaluated at surgery and at 3 and 9 months postoperatively using bidirectional echocardiographic and angiographic methods. After sacrifice, histological and radiological analyses were performed. The mean weight of the animals was 4.2 +/- 1.1 kg at implantation and 43.1 +/- 6.2 kg at sacrifice. There was a significant increase in mean valve area from 139.9 +/- 18.0 mm2 at implantation to 443.5 +/- 89.2 mm2 at 12 months. Pre-sacrifice angiography showed no transvalvular gradient, and radiographic analysis did not reveal significant conduit wall or leaflet calcification in any of the animals. Histological examination of the grafts demonstrated total integration, with native-like intact valve leaflets. Thus functional evaluation, echocardiography, and histology demonstrated growth of the grafts with completely endothelialized and apparently normal pulmonary valve leaflets without calcification.

Two-dimensional, M-mode and Doppler-derived echocardiographic parameters in sedated healthy growing female sheep

“…Moreover, new strategies for the correction of congenital heart defects, which require surgical reconstruction of the right ventricle to pulmonary artery continuity using tissue-engineered vascular grafts, have been tested in lambs because the growth of the animal was considered to be of primary importance. 9,10 Infants in whom prosthetic conduits are implanted, in fact, require more than one intervention, in order to adapt the prosthetic valve or conduit size to the heart's dimensions which increase with age. 9 In all the above-mentioned studies, as well as in the course of routine clinical activity, echocardiography is used as a non-invasive tool for the evaluation of cardiac morphology and function, being a sensitive and accurate method for measuring changes in chamber dimensions and thickness of the cardiac walls in response to a pathological process.…”

Calcification in Pulmonary Heart Valve Tissue Engineering

“…The original search by Uiterwijk et al 20 identified 817 articles, of which 80 were included in qualitative analysis for this study, after reassessment of studies that reported on additional data from previously reported animals ( Supplemental Figure 1 ). All 80 studies 37 , 39 , 40 , 41 , 42 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 ,…”

“…Microcalcifications were often missed with macroscopic assessment when compared to other methods of analysis. 42 , 44 , 60 , 69 , 75 , 84 , 105 For 5 studies, the description of calcification was not applicable because of their short follow-up time (<1 week) and 22 studies failed to describe calcification. The preferred analysis method was histology ( Figure 3C , 33 studies, 75%), sometimes combined with additional methods to characterize calcification.…”

Replacement of pulmonary artery trunk in sheep using tubular valved heterograft in non-aldehydic preservation

“…The main disadvantage of glutaraldehyde fixation of bioprostheses is the resulting tissue calcification over time [1,16,17], which favors the dysfunction and the need for surgical replacement of the prosthesis. The current challenge of tissue engineering is to study and propose the creation of replacement tissue and heart valves from biological and artificial structures that are biocompatible, non-thrombogenic, non-teratogenic, (25) demonstrated that porcine pulmonary xenograft with L-Hydro R preservation placed in the pulmonary position of sheep newborns and followed into adulthood presents growth of the graft, absence of calcification and preservation of pulmonary valve function.…”