Novel thermosensitive hydrogel injection inhibits post‐infarct ventricle remodelling

Abstract

AimsMyocardial infarction (MI) remains the commonest cause of cardiac-related death throughout the world. Adverse cardiac remodelling and progressive heart failure after MI are associated with excessive and continuous damage of the extracellular matrix (ECM). In this study, we hypothesized that implantation of hydrogel into infarcted myocardium could replace the damaged ECM, thicken the infarcted wall, and inhibit cardiac remodelling. Methods and resultsMI was induced in rabbits by coronary artery ligation; 4 days later, 200 mL Dex-PCL-HEMA/PNIPAAm gel solution was injected into the infarcted myocardium. Injection of phosphate-buffered saline served as control. Thirty days after treatment, histological analysis indicated that injection of the biomaterial prevented scar expansion and wall thinning compared with controls. Echocardiography studies showed that injection of hydrogel increased left ventricular ejection fraction and attenuated left ventricular systolic and diastolic dilatation. Haemodynamic analysis demonstrated improved cardiac function following implantation of the hydrogel. ConclusionThese results suggest that injection of thermosensitive Dex-PCL-HEMA/PNIPAAm hydrogel is an effective strategy that prevents adverse cardiac remodelling and dysfunction in MI rabbits.--

Injectable Acellular Hydrogels for Cardiac Repair

“…When injected 5 min post-MI in a rat model, the hydrogel-treated groups showed a significant reduction in infarct size, LVEDD, LVESD, and an increase in FS compared to PBS injection controls. No increase in neovascularization was observed [32]. In 1-week-old infarcts in a rabbit model, significant improvements in thickness, infarct size, LVEDD, LVESD, and EF were observed with no increase in microvessel density [24].…”

“…One synthetic thermosensitive polymer, comprised of dextran (Dex) grafted poly (caprolactone)-2-hydroxyethyl methacrylate (PCL-HEMA) and copolymerized with poly(N-isopropylacrylamide) (PNIPAAm) termed Dex-PCL-HEMA/PNIPAAm, was developed to gel in situ. Material injections were performed 4 days post-MI in a rabbit model and resulted in significant reductions in infarct scar and improvement in EF and LV end diastolic and systolic diameter (LVEDD and LVESD) compared to PBS control injections when assessed 30 days after injection [32]. Significant thickening was observed despite no histological evidence of material remaining.…”

“…Another synthetic material consisting of α-cyclodextrin (α-CD) and poly(ethylene glycol) (MPEG-PCL-MPEG) triblock copolymer that has the ability to gel in situ has also demonstrated therapeutic benefits when injected to target LV remodeling [24,32]. Degradation can be controlled by the PCL block, and hydrogels were formed upon mixing the linear MPEG-PCL-MPEG polymer with α-CD.…”

“…However, these approaches are limited by the invasive procedure in which they are applied, and clinical adoption has not occurred. In order to circumvent the invasive surgical placement of restraining devices early post-MI, our group and others have begun to explore the use of injectable materials, and specifically hydrogels, to limit infarct expansion and normalize the regional stress distribution [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35].…”

Heart regeneration after myocardial infarction using synthetic biomaterials

“…Nowadays synthetic materials have achieved high degrees of biodegradation and biocompatibility, like their natural counterparts. In fact, cardiac administration of synthetic hydrogels has proved to be effective in terms of promoting contractile phenotype smooth muscle tissue formation [46,47], preventing LV remodeling and scar expansion and improving cardiac function [48][49][50][51]. Interestingly, the timing of administration seems to be important because hydrogels assumed markedly different morphologies that determined heart remodeling.…”