Customized 3D-printed occluders enabling the reproduction of consistent and stable heart failure in swine models

摘要

Reproducibility of clinical output is important when investigating therapeutic efficacy in pre-clinical animal studies.Due to its physiological relevance,a swine myocardial infarction(MI)model has been widely used to evaluate the effectiveness of stem cells or tissue-engineered constructs for ischemic heart diseases.Several methods are used to induce MI in the swine model.However,it is difficult,using these approaches,to obtain a similar level of functional outcomes from a group of animals due to interpersonal variation,leading to increased experimental cost.Hence,in order to minimize human intervention,we developed an approach to use a customized occluder that has dimensional similarities with that of the coronary artery of animals in the case of the swine model.We carried out angiography to measure the diameter of the middle left anterior descending artery of each individual animal to fabricate the customized occluder using a 3D-printing system.The fabricated occluder contained a central hole smaller than that of the targeted middle left anterior descending artery to mimic an atherosclerotic coronary artery that has an approximately 20%blocked condition.Interestingly,the 3D-printed occluder can provide continuous blood flow through the central pore,indicating a high survival rate(88%)of up to 28 days post-operation.This method showed the possibility of creating consistent myocardial infarction induction as compared to the conventional representative closed-chest method(50%survival rate),thus highlighting how our method can have a profound effect on accelerating reliable experiments for developing new therapeutic approaches to ischemic heart diseases.