Establishing a pre-clinical growing animal model to test a tissue engineered valved pulmonary conduit

Abstract

Background: Many valvular pathologies of the heart may be only sufficiently treated by replacement of the valve if a reconstruction is not feasible. However, structural deterioration, thrombosis with thromboembolic events and infective endocarditis are commonly encountered complications over time and often demand a re-operation. In congenital heart disease the lack of small diameter valves with the potential to grow poses additional challenges and limits treatment options to homo-or xenograft implants.Methods: In this study, a chronic sheep model (24 months follow-up), a self-constructed valved conduit was created out of a tissue engineered (TE) patch (CorMatrix® Cardiovascular, Inc, USA) and implanted in orthotopic right ventricular (RV)-pulmonary artery (PA) position. Thereafter, the sheep were regularly monitored by clinical, laboratory and echocardiographic examinations to evaluate cardiac function and the implanted RV-PA-conduit.Discussion: Here, we summarize the study protocol and our experiences during the perioperative phase and the follow up period and explain how we constructed a valved conduit out of a commercially available TE patch.

Wharton’s Jelly–Mesenchymal Stem Cell–Engineered Conduit for Pulmonary Artery Reconstruction in Growing Piglets

“…Porcine SIS (ProxiCor), which is being used in various clinical applications of cardiovascular surgery with no evidence of immune rejection, has also been utilized in different animal models of valved conduit reconstruction, with ambiguous results. 23 , 24 , 25 , 26 , 27 However, the biology and the biomechanics of the vascular wall significantly differ from those of the valvar leaflets; therefore, we believe that in a preclinical setting the 2 components must be addressed and analyzed separately as a first step.…”

“…Multiple investigators have reported failures with SIS over the past 10 years, both in preclinical and clinical scenarios. 25 , 26 , 36 , 37 , 38 , 39 , 40 However, several papers have focused on this biomaterial used as a valve leaflet patch and/or in high pressure districts 37 , 40 ; moreover, histologic changes in preclinical studies were mostly assessed on nonseeded grafts. 23 , 24 , 25 , 27 It could be argued that seeded porcine SIS might not exhibit the same behavior observed in this work when implanted in humans as a result of cross-species immune reaction to the graft.…”

Pulmonary valve tissue engineering strategies in large animal models

“…synthetic and natural scaffold studies), and the mean number of animals per experimental group (comparison) was low (n = 3 per experimental group). Only four experimental groups (27 animals) had a follow-up time of 20–24 months [ 47 , 74 , 102 ]. While valve calcification might be evaluated in a relative short time period, TE of heart valves has the aim to create prostheses at least not inferior in durability compared to the currently available valve prostheses.…”

Challenges in Perioperative Animal Care for Orthotopic Implantation of Tissue-Engineered Pulmonary Valves in the Ovine Model

“…Metamizole and ketorolac were continued for 5-7 days after the surgery to provide postoperative analgesia. Metamizole (20 mg/kg) in combination with carprofen (4.0 mg/kg) was reported by Knirsch et al [27] for pain control. To avoid tracheal and/ or laryngeal damage and facilitate endotracheal intubation, a non-depolarizing neuromuscular blocking agent (atracurium) was used in all cases.…”